lectureI 5th March2012 - Jagiellonian...
Transcript of lectureI 5th March2012 - Jagiellonian...
![Page 1: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/1.jpg)
Angiogenesis – background
lecture I
5th March 2012
![Page 2: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/2.jpg)
AngiogenesisAngiogenesis
� An�gi�o�gen�e����sis (an-jee-o-JEN-uh-sis):
angei-, angeio-, vessel or blood vessel,
genesis-, origin or birth
angiogenesis:
formation of new blood vessels via
extension or remodeling from existing
capillaries
![Page 3: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/3.jpg)
CirculatoryCirculatory system system andand bloodblood vesselsvessels
![Page 4: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/4.jpg)
BloodBlood vesselsvessels
Cleaver O & Melton DA, Nature Med., June 2003
![Page 5: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/5.jpg)
pericytes
pericytes
pericytes
CapillariesCapillaries withwith pericytespericytes
![Page 6: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/6.jpg)
Examples of vascular defectsExamples of vascular defects
![Page 7: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/7.jpg)
TheThe vascularvascular wallwall
![Page 8: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/8.jpg)
![Page 9: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/9.jpg)
![Page 10: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/10.jpg)
vascular wall
remodeling
EndotheliumEndothelium regulatesregulates
vascular tone
thrombosis
fibrinolysis
inflammation
angiogenesis
![Page 11: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/11.jpg)
Tousoulis, et al., Heart 2005;
Endothelial cell functionsEndothelial cell functions
• Maintaining the vascular tone: Vasodilation and Vasoconstriction
![Page 12: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/12.jpg)
BloodBlood vesselvessel formationformation -- shortshort historyhistory ofof studiesstudies
• Roman physician Claudius Galen of Pergamon (129–199) found
that vessels are filled with blood. But he claimed that blood is
produced in the liver.
• Then, sir William Harvey (1578 -1657) discovered the circulation
of blood
• Harvey proved that blood flows around the body. He stated that
blood was carried away from the heart by arteries and returns to
the heart through veins.
•• Harvey proved that the heart is a pump
that recirculates the blood
![Page 13: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/13.jpg)
William Harvey - 1628
the first systematic description of circulatory system
(1578-1657)
![Page 14: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/14.jpg)
HarveyHarvey’’s Methodss Methods
Harvey was very scientific in his methods. These included:
• Dissecting cold blooded animals (e.g. reptiles) to observe the movement of muscle around the heart.
• Dissecting humans to gain a knowledge of the heart.
• He accurately calculated the amount of blood in the body.
![Page 15: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/15.jpg)
• The word „angiogenesis” was used for the first time in 1787 by
british surgeon, Dr. John Hunter, to describe the growth of blood
vessels in reindeer antler.
BloodBlood vesselvessel formationformation -- shortshort historyhistory ofof studiesstudies
• The term „endothelium” was introduced by Wilhelm His in
1865 to differentiate the inner lining of body cavities from
„epithelium”
• In 1661 Marcello Malpighi observed capillaries using
chicken embryo model
Die Häute und Höhlen des Körpers.
Basel, Schwighauser, 1865.
A new classification of tissues based on histogenesis. In the present work, His put forth the basic concepts of
tissue embryology. Using serial sections and three-dimensional models to illustrate his theories, he showed that
the serous spaces in the embryo are mesodermal in origin and that they are lined by the special layer which he
was the first to term "endothelial"
![Page 16: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/16.jpg)
• End of XIX/begining XX century Henryk Hoyer –
(Jagiellonian University) – description of lymphatic system
• Detailed study on vasculogenesis in chick embryo and
lymphangiogenesis by Florence Sabin
BloodBlood vesselvessel formationformation -- shortshort historyhistory ofof studiesstudies
Diagram of the organization of lymphatic and
vein systems in chordate
3, dogfish; 4, fish; 5, newt and salamander; 6,
frog and toad; 7, lizard; 8, crocodile; 9, bird;
10, mammals.
Distribution of the surface lymphatic
veins on the head of trout (Salmo
trutta).
![Page 17: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/17.jpg)
BloodBlood vesselvessel formationformation -- shortshort historyhistory ofof studiesstudies
• Gimbrone MA Jr, Cotran RS, Folkman J.
Endothelial regeneration: studies with human endothelial cells in culture.
Ser Haematol. 1973;6(4):453-5
• Jaffe EA, Nachman RL, Becker CG, Minick CR
Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and
immunologic criteria.
J Clin Invest. 1973 Nov;52(11):2745-56
Endothelial cells were isolated from freshly obtained human umbilical cords by collagenase digestion of the interior of the umbilical
vein. The cells were grown in tissue culture as a homogeneous population for periods up to 5 mo and some lines were subcultured for
10 serial passages.…..
• Ades EW, Candal FJ, Swerlick RA, George VG, Summers S, Bosse DC, Lawley TJ.
HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J Invest
Dermatol. 1992 Dec;99(6):683-90.
![Page 18: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/18.jpg)
Model Model organismsorganisms inin vascularvascular researchresearch
![Page 19: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/19.jpg)
Transgenic zebrafish allowTransgenic zebrafish allowss analysis of analysis of
endothelial cells in living embryosendothelial cells in living embryos
Dorsal AortaDorsal Aorta(DA)(DA)
Posterior Cardinal Vein(PCV)
Intersegmental VesselsIntersegmental Vessels(Se)(Se)
Dorsal Longitudinal Anastomotic VesselDorsal Longitudinal Anastomotic Vessel(DLAV)(DLAV)
Caudal Vein Caudal Vein Capillary PlexusCapillary Plexus
![Page 20: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/20.jpg)
VEGFVEGF isis required for vasculogenesis in zebrafishrequired for vasculogenesis in zebrafish
Nasevicius et al., 2000
Microangiography allows high resolution mapping of mature vessels
![Page 21: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/21.jpg)
EndothelialEndothelial cells cells
The crucial player in blood vessel formation
Endothelial cells in culture – cobblestone appearance
![Page 22: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/22.jpg)
Human microvascular endothelial cells (HMEC-1)
• main players in angiogenesis
• immortalized cell line
• generate detectable amount of VEGF
• extended life span
Human umbilical vein endothelial cell line (HUVEC)
• macrovascular cells
• produce very small amount of VEGF
• dependent on growth factors
• limited life span
VariousVarious typestypes ofof endothelialendothelial cells cells
![Page 23: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/23.jpg)
IsolationIsolation ofof HUVEC HUVEC cellscells
![Page 24: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/24.jpg)
Endoglin is an auxiliary receptor for the transforming growth factor-beta family of cytokines
and is required for angiogenesis and heart development.
vWF - Von Willebrand factor
QuiescentQuiescent andand angiogenic angiogenic endothelialendothelial cellscells
![Page 25: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/25.jpg)
Endothelial cell markers used to identify Endothelial cell markers used to identify
microvasculature in tissuesmicrovasculature in tissues
Scavenger receptorUptake of Ac-LDL
Factor VIII von Willebrand Factor (vWF)
VEGFVEGFR-2
AngiopoietinsTie-2
Ephrin B2EphB4
EphB4Ephrin B2
ET-1Endothelin receptor B (ETBR)
CD144 homotypic interactionCD144 (VE-cadherin)
ThrombinCD141 (thrombomodulin)
VLA-4 integrinCD106 (VCAM-1)
TGF-β1 and –β3CD105 (endoglin)
Sialyl-Lewis-X antigen and other carbohydratesCD62E (E-selectin)
LFA-1 integrinCD54 (ICAM-1)
L-selectinCD34
CD31 on endothelial cells, leukocytes; glycosaminoglycansCD31 (PECAM-1)
LigandMarker
![Page 26: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/26.jpg)
kidney small intestine liver
Cells in an organ under the control of Cells in an organ under the control of
organ specific influencesorgan specific influences
![Page 27: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/27.jpg)
MorphologicalMorphological differentiationdifferentiation ofof capillariescapillaries
Skeletal muscle, heart,
lung, brainEndocrine and exocrine organs
Cleaver O & Melton DA, Nature Med., June 2003
![Page 28: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/28.jpg)
CONTINUOUS =
UNFENESTRATEDBasement
membrane
Endothelial
cellJunctions
Occluding
Gap
Adherens
Vesicles
ContinousContinous capillariescapillaries
![Page 29: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/29.jpg)
Fenestrae/pore
80-100 nm
Endothelial
cell
Basement
membrane
Vesicles /
caveolae
FenestratedFenestrated capillariescapillaries
![Page 30: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/30.jpg)
Endothelial cell
DiscontinousDiscontinous capillariescapillaries
Lack of
basement
membrane !
* sinusoids
![Page 31: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/31.jpg)
Basal lamina
Endothelial
cellJunctions
Caveolae &
Vesicles
2. TRANSCYTOSIS
3. INTER-CELLULAR
PASSAGE
4. MEMBRANE
TRANSPORTERS
1. DIFFUSION
ContinousContinous capillariescapillaries –– transporttransport
Typical for
muscle & skin
![Page 32: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/32.jpg)
fenestrae/pore 4. MEMBRANE
TRANSPORTERS
3. INTER-
CELLULAR
PASSAGE ?
2. TRANSCYTOSIS
1. DIFFUSION
5. THROUGH
PORES
Typical for gut, kidney,
& endocrine glands
Fenestrated capillaries – transport
![Page 33: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/33.jpg)
HowHow thethe bloodblood vesselsvessels areare formedformed??
Susuma Nishinaga/Science Photo Library
Blood vessels in the small intestine
![Page 34: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/34.jpg)
BloodBlood vesselvessel formationformation
a) vasculogenesis:
de novo blood vessel generation from
vascular progenitor cells
b) angiogenesis:
formation of new blood vessels via extension
or remodeling of existing blood vessels
c) arteriogenesis:
maturation of blood vessels via increasing
the lumen of vessels
![Page 35: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/35.jpg)
BloodBlood vesselvessel formationformation
• Vasculogenesis:
a) during embryonic development;
• Angiogenesis:
a) embryonic development
b) adulthood: wound healing, menstrual
cycle, tumor-angiogenesis…
b) during adulthood associated with
circulating progenitor cells
![Page 36: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/36.jpg)
PhysiologicalPhysiological angiogenesisangiogenesis inin adultsadults isis restrictedrestricted
placenta uterus
Hair growthWound healing
![Page 37: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/37.jpg)
New New capillarycapillary formationformation inin responseresponse to to woundingwounding
![Page 38: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/38.jpg)
AngiogenesisAngiogenesis maymay be be impairedimpaired inin many many diseasesdiseases
CardiovascularCardiovascular
diseasesdiseases
![Page 39: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/39.jpg)
angioblastcapillary
bFGF
VEGF
VEGF
Ang1, bFGF
Vasculogenesiscapillaries are formed from
vascular progenitor cells
Angiogenesisformation of new blood vessels
from pre-existing vessels
Arteriogenesisformation of mature blood
vessels; differentiation into
veins and arteries
ThreeThree waysways ofof formationformation ofof bloodblood vesselsvessels
MCP-1, PDGF
Ang-2
![Page 40: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/40.jpg)
Major Major growthgrowth factorsfactors andand receptorsreceptors involvedinvolved
inin bloodblood vesselsvessels formationformation
VEGF – vascular endothelial growth factors
VEGF-A – crucial mediator of angiogenesis
VEGF-R – receptors for vascular endothelial growth factors
Angiopoietins (Ang-1, 2)
Tie- 2 – receptor for Ang-1, -2
FGFs – fibroblast growth factors
PDGF – platelet-derived growth factor
![Page 41: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/41.jpg)
Angiogenesis
• Majority of vascular development occurs
via angiogenesis
• Growth of new blood vessels from
existing vessels
• Two distinct mechanisms available
a) sprouting angiogenesis
b) intussusceptive angiogenesis
![Page 42: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/42.jpg)
SproutingSprouting angiogenesisangiogenesis
• Sprouting: invasion of new capillaries into
unvascularized tissue from existing mature
vasculature
- degradation of matrix proteins
- detachment and migration of ECs
- proliferation
![Page 43: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/43.jpg)
SproutingSprouting angiogenesisangiogenesis
![Page 44: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/44.jpg)
IntussusceptiveIntussusceptive oror non non sproutingsprouting angiogenesisangiogenesis
- remodelling of existing vessels
- interendothelial contact is needed
- splits into two vessels
![Page 45: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/45.jpg)
a: Remodeling: A pillar appears in closeproximity of the branching angle
b,c: From the pillar a fold developstoward the tissue of the branching angleand finally the pillar tissue merges withthe interstitium of the branching angle
d: As a result, the branching angle isrelocated proximalad and the angle isaltered
e: Pruning: A column of pillars arisesclose to the branching angleThe pillars can merge along a lineindicated by the arrows. The eccentriclocation of the pillars can lead to alterations in the diameter of a vascularbranch.
f: Ultimately, a branch can be completelypruned by repetition of the process(arrows along a theoretical line).
Scanning electron micrographs of chicken chorioallantoic membrane (CAM) vessels showing intussusceptive branching remodeling:
Burri, PH Dev Dyn. 2004
![Page 46: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/46.jpg)
?
StagesStages ofof angiogenesisangiogenesis
![Page 47: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/47.jpg)
Angiogenesis is a dynamic and context determined processAngiogenesis is a dynamic and context determined process
![Page 48: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/48.jpg)
VascularVascular
EndothelialEndothelial
GrowthGrowth
FactorFactor
VV
EE
GG
FF
VascularVascular
PermeabilityPermeability
FactorFactor
VV
PP
FF
1983,1983,
Dr H. Dr H. DvorakDvorak
1989, 1989,
Dr N. FerraraDr N. Ferrara
Dr J. Dr J. PlouetPlouet
=
vascularvascular permeabilitypermeability factorfactor
endothelialendothelial cellcell survivalsurvival factorfactor
endothelialendothelial cellcell proliferationproliferation
endothelialendothelial cellcell migrationmigration
MainMain proangiogenicproangiogenic factorfactor
![Page 49: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/49.jpg)
StagesStages ofof angiogenesisangiogenesis
1. increase in vessel permeability
2. loosening of pericyte contact
3. proteinase release from endothelial cells
4. digestion of basement membrane and extracellular matrix
5. migration and proliferation of endothelial cells
6. formation of vascular structures
7. fusion of new vessels
8. initiation of blood flow
inhibition of endothelial cell proliferation
inhibition of the migration of endothelial cells
9. formation of basement membrane
![Page 50: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/50.jpg)
Angiogenesis Angiogenesis -- Basement Membrane BreakdownBasement Membrane Breakdown
Smooth Muscle
Cells
Endothelium
Basement
Membrane
Matrix
metalloproteinases
Angiogenic
Stimulus
(VEGF)
![Page 51: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/51.jpg)
CrucialCrucial role role ofof metalloproteinasesmetalloproteinases inin angiogenesisangiogenesis
MMP-2 – gelatinase AMMP-9 – gelatinase B
![Page 52: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/52.jpg)
elastinmetalloelastase (MMP-12)
type V collagenEnamelysin (MMP-20)
gelatinMMP-19 (RASI-1)Others MMP (examples)
type IV, V collagen, gelatinGelatinase B (MMP-9)
type I, IV, V and fibrillar
collagens; gelatin
Gelatinase A (MMP-2)Gelatinases
MT4-MMP (MMP-17)
gelatinase AMT3-MMP (MMP-16)
gelatinase AMT2-MMP (MMP-15)
gelatinase A, fibrillar
collagens, proteoglycans,
ECM glycoproteins
MT1-MMP (MMP-14)The membrane-bound
MMPs
MMP-26 (Matrilysin-2, endometase)
laminin, fibronectin, non-fibrillar collagensMatrilysin (MMP-7) PUMPMatrilysins
Stromelysin-3 (MMP-11)
Stromelysin-2 (MMP-10)
laminin, fibronectin,
non-fibrillar collagens
Stromelysin-1 (MMP-3)Stromelysins
MMP-18 (Collagenase 4, xenopus collagenase)
Collagenase-3 (MMP-13)
Neutrophil Collagenase (MMP-8)
fibrillar collagensInterstitial Collagenase (MMP-1)Collagenases
ECM SubstrateMMP NameMMP family
MatrixMatrix metalloproteinasesmetalloproteinases
![Page 53: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/53.jpg)
Prodomain Catalytic domain Hemopexin
PRCGxPD
gelatin
binding
Zn2+
Zn2+
Zn2+
Zn2+
Zn2+
Collagenase family
Gelatinase family
MT-MMPs
MMP-7, MMP-23,
MMP-26
Hinge
region
Stromelysin family
Transmembrane
MatrixMatrix metalloproteinasesmetalloproteinases
![Page 54: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/54.jpg)
MMPsMMPs areare pro pro andand antianti--angiogenicangiogenic
PRO-ANGIOGENIC
• Degradation of basement membrane and ECM to allow for cell
detachment and migration
• Cleavage of VE-cadherin cell-cell adhesion
• Release of active VEGF from ECM stores
• Cleavage of basement membrane to release bFGF and to release
and activate TGFβ
![Page 55: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/55.jpg)
MMPsMMPs areare pro pro andand antianti--angiogenicangiogenic
ANTI-ANGIOGENIC
• Generation of antiangiogenic factors
- angiostatin from plasminogen
- endostatin, tumostatin, arrestin, and canstatin from type
XVIII and IV collagen
![Page 56: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/56.jpg)
Tissue inhibitors of
metalloproteinases (TIMPs)
Matrix metalloproteinases (MMPs)
zinc-dependent endopeptidases
Balance between MMPs and TIMPsBalanceBalance betweenbetween MMPsMMPs andand TIMPsTIMPs
![Page 57: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/57.jpg)
StagesStages ofof angiogenesisangiogenesis
1. increase in vessel permeability
2. loosening of pericyte contact
3. proteinase release from endothelial cells
4. digestion of basement membrane and extracellular matrix
5. migration and proliferation of endothelial cells
6. formation of vascular structures
7. fusion of new vessels
8. initiation of blood flow
inhibition of endothelial cell proliferation
inhibition of the migration of endothelial cells
9. formation of basement membrane
![Page 58: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/58.jpg)
Angiogenesis - Endothelial Cell Migration
Endothelium
Nascent
Vascular Sprouts
VEGF
Smooth Muscle
Cells
Basement
Membrane
![Page 59: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/59.jpg)
StagesStages ofof angiogenesisangiogenesis
1. increase in vessel permeability
2. loosening of pericyte contact
3. proteinase release from endothelial cells
4. digestion of basement membrane and extracellular matrix
5. migration and proliferation of endothelial cells
6. formation of vascular structures
7. fusion of new vessels
8. initiation of blood flow
inhibition of endothelial cell proliferation
inhibition of the migration of endothelial cells
9. formation of basement membrane
![Page 60: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/60.jpg)
Angiogenesis Angiogenesis -- Endothelial Cell ProliferationEndothelial Cell Proliferation
Endothelium
VEGF
Sprout
ElongationSmooth Muscle
Cells
Basement
Membrane
![Page 61: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/61.jpg)
Angiogenesis Angiogenesis -- Capillary MorphogenesisCapillary Morphogenesis
Endothelium
VEGF
New
Lumen
FormationSmooth Muscle
Cells
Basement
Membrane
![Page 62: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/62.jpg)
StagesStages ofof angiogenesisangiogenesis
1. increase in vessel permeability
2. loosening of pericyte contact
3. proteinase release from endothelial cells
4. digestion of basement membrane and extracellular matrix
5. migration and proliferation of endothelial cells
6. formation of vascular structures
7. fusion of new vessels
8. initiation of blood flow
inhibition of endothelial cell proliferation
inhibition of the migration of endothelial cells
9. formation of basement membrane
![Page 63: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/63.jpg)
Angiogenesis Angiogenesis -- Vascular MaturationVascular Maturation
Endothelium
VEGF
SMC, pericyte
recruitment
Smooth Muscle
Cells
Basement
Membrane
![Page 64: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/64.jpg)
SummarySummary ofof thethe mechanismsmechanisms ofof angiogenesisangiogenesis
arterio/venous
differentiation(ephrins/Eph)
![Page 65: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/65.jpg)
Vessel maturation
and regression
![Page 66: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/66.jpg)
AngiogenesisAngiogenesis isis dependent on dependent on thethe balancebalance
betweenbetween propro-- andand antianti--angiogenicangiogenic mediatorsmediators
![Page 67: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/67.jpg)
VesselVessel maintainancemaintainance versusversus vesselvessel regressionregression
Carmeliet, Nature Med. 2003
![Page 68: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/68.jpg)
AngiogenesisAngiogenesis maymay be be impairedimpaired inin many many diseasesdiseases
CardiovascularCardiovascular
diseasesdiseases
![Page 69: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/69.jpg)
VEGF, bFGF, EGF
tumor
Small avascular
tumorTumor secretion of angiogenic factors
is triggered by hypoxia
VEGF, bFGF, EGF
tumor
hypoxia in
the center of tumorANGIOGENIC SWITCH
Pro-angiogenic factors stimulate the migration and
proliferation of endothelial cellsRapid tumor growth and metastasis
VEGF, bFGF, EGF
Tumor
expansion
Tumor Tumor angiogenesisangiogenesis
![Page 70: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/70.jpg)
Vessel intussusception
EPCs Lymphangiogenesis
blood vessel
tumor
EPC
tumor
blood vessel
bone
marrowtumor
lymphatic vessel
DifferentDifferent mechanismsmechanisms ofof bloodblood formationformation inin tumorstumors
Loboda et al., 2011
![Page 71: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/71.jpg)
DifferentDifferent mechanismsmechanisms ofof bloodblood formationformation inin tumorstumors
Vasculogenic mimicry
tumor
endothelial cell
VM cell
Vessel co-option
blood vessel
tumor
Loboda et al., 2011
![Page 72: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/72.jpg)
TheThe mechanismsmechanisms involvedinvolved inin bloodblood vesselvessel formationformation areare
evolutionaryevolutionary veryvery conservativeconservative
![Page 73: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/73.jpg)
Schweitzer et al. Science 2005.
DissolvedDissolved T. T. rexrex bonebone yieldedyielded flexibleflexible, , branchingbranching
vesselsvessels somesome ofof whichwhich containcontain cellcell--likelike structuresstructures
![Page 74: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/74.jpg)
PresencePresence ofof VEGFVEGF--likelike proteinsproteins inin differentdifferent animalsanimals
• In the nematode Caenorhabditis elegans four possible
homologs of PDGF/VEGF receptors (VER-1 to VER-4) and
one ligand (PVF-1) are known
• PVF-1 has the ability to bind to human receptors VEGFR-
1 and VEGFR-2 and to induce angiogenesis in two model
systems derived from vertebrates
Jorgensen & Mango, Nat Rev Gen 2002; Tarsitano et al. FASEB J 2006.
Control HUVEC HUVEC + VEGF HUVEC + PVF-1
![Page 75: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/75.jpg)
O’Farrell, J Clin Invest 2001
DrosophilaDrosophila melanogastermelanogaster
respiratory (respiratory (trachealtracheal) system) system
- Branching tubular system of trachea delivers oxygen to
the tissues of insects.
- Its development shows parallels to the angiogenesis
- Branchless (a homolog of mammalian FGF), PVF1, PVF2, PVF3 (homologs of
mammalian VEGF/PDGF) and PVR receptor regulate the migration of early
hemocytes and are necessary for formation of tracheal system.
Tracheal tree of Drosophila embryo
DB – dorsal branch; DT – dorsal trunk;
GB – ganglionic branch; VB – visceral branch
![Page 76: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/76.jpg)
O’Farrell, J Clin Invest 2001
DrosophilaDrosophila melanogastermelanogaster
respiratory (respiratory (trachealtracheal) system) system
- The cellular morphogenesis by which insect tracheal
cells produce fine terminal branches resembles capillary
formation of endothelial cells.
- Like capillaries, the branching of terminal trachea is
not sterotyped, but is regulated by the availability of
oxygen.
- Despite the extensive differences in their designs, the oxygen
delivery systems of insects and mammals may
have evolved from a common primitive system
present in evolutionary predecessors of
both groups.
Tracheal system in the
muscle.
(Corrosion cast)
Trachea
![Page 77: lectureI 5th March2012 - Jagiellonian Universitybiotka.mol.uj.edu.pl/zbm/handouts/2012/AL/lecture_1... · 80-100 nm Endothelial cell Basement membrane Vesicles/ caveolae Fenestrated](https://reader030.fdocuments.net/reader030/viewer/2022011914/5fbf058cd57a391a5228e83a/html5/thumbnails/77.jpg)
Take home messages
1. Endothelial cells form the inner part of blood vessels
2. Three main mechanisms of formation of blood vessels are
known
3. Numerous mediators are involved in blood vessels formation
4. Physiological angiogenesis in adults is restricted, but it is a
significant component of numerous diseases, such as cancer
or atherosclerosis
5. Angiogenesis is a multi-step process including activation of
endothelial cells, their proliferation and migration