Cardiovascular System - Blood Vessel Development

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Notice - Mark Hill
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Introduction

Blood develops initially within the core of "blood islands" in the mesoderm.

During development, there follows a series of "relocations" of the stem cells to different organs within the embryo.

In the adult, these stem cells are located in the bone marrow. At the time when blood first forms, there are no bones!


Angioblasts initially form small cell clusters (blood islands) within the embryonic and extraembryonic mesoderm. These blood islands extend and fuse together making a primordial vascular network. Within these islands the peripheral cells form endothelial cells while the core cells form blood cells (haemocytoblasts).


Fetal blood vessel

Recent work has shown that the formation of the initial endothelial tube is by a process of coalescence of cellular vacuoles within the developing endothelial cells, which fuse together without cytoplasmic mixing to form the blood vessel lumen.


Blood Vessel Formation
(Image: Developmental biology: The hole picture Keith Mostov and Fernando Martin-Belmonte Nature 442, 363-364 27 July 2006)


Cardiovascular Links: cardiovascular | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | 2016 Cardiac Review | heart | coronary circulation | heart valve | heart rate | Circulation | blood | blood vessel | blood vessel histology | heart histology | Lymphatic | ductus venosus | spleen | Stage 22 | cardiovascular abnormalities | OMIM | 2012 ECHO Meeting | Category:Cardiovascular
Historic Embryology - Cardiovascular 
1902 Vena cava inferior | 1905 Brain Blood Vessels | 1909 Cervical Veins | 1909 Dorsal aorta and umbilical veins | 1912 Heart | 1912 Human Heart | 1914 Earliest Blood-Vessels | 1915 Congenital Cardiac Disease | 1915 Dura Venous Sinuses | 1916 Blood cell origin | 1916 Pars Membranacea Septi | 1919 Lower Limb Arteries | 1921 Human Brain Vascular | 1921 Spleen | 1922 Aortic-Arch System | 1922 Pig Forelimb Arteries | 1922 Chicken Pulmonary | 1923 Head Subcutaneous Plexus | 1923 Ductus Venosus | 1925 Venous Development | 1927 Stage 11 Heart | 1928 Heart Blood Flow | 1935 Aorta | 1935 Venous valves | 1938 Pars Membranacea Septi | 1938 Foramen Ovale | 1939 Atrio-Ventricular Valves | 1940 Vena cava inferior | 1940 Early Hematopoiesis | 1941 Blood Formation | 1942 Truncus and Conus Partitioning | Ziegler Heart Models | 1951 Heart Movie | 1954 Week 9 Heart | 1957 Cranial venous system | 1959 Brain Arterial Anastomoses | Historic Embryology Papers | 2012 ECHO Meeting | 2016 Cardiac Review | Historic Disclaimer


Some Recent Findings

[1]Developmental origin of smooth muscle cells in the descending aorta in mice. Development. 2008 May;135(10):1823-32. (More? [../Notes/skmus6.htm Musculoskeletal Development - Mesoderm/Somite])

"Aortic smooth muscle cells (SMCs) have been proposed to derive from lateral plate mesoderm. ....(these results) suggested that all SMCs in the adult descending aorta derive from the somites, whereas no contribution was recorded from lateral plate mesoderm."

[2]Endothelial expression of the Notch ligand Jagged1 is required for vascular smooth muscle development. Proc Natl Acad Sci U S A. 2008 Feb 1;

"The Notch ligand Jagged1 (Jag1) is essential for vascular remodeling. ...Jag1 null phenotype. These embryos show striking deficits in vascular smooth muscle, whereas endothelial Notch activation and arterial-venous differentiation appear normal."

[3]"In sprouting angiogenesis, specialized endothelial tip cells lead the outgrowth of blood-vessel sprouts towards gradients of vascular endothelial growth factor (VEGF)-A. ...suggest that Dll4-Notch1 signalling between the endothelial cells within the angiogenic sprout serves to restrict tip-cell formation in response to VEGF, thereby establishing the adequate ratio between tip and stalk cells required for correct sprouting and branching patterns."

[4] "More than 25 years ago, in some of the first endothelial cell culture experiments in vitro, Folkman and Haudenschild described "longitudinal vacuoles" that "appeared to be extruded and connected from one cell to the next" "...Here we use high-resolution time-lapse two-photon imaging of transgenic zebrafish to examine how endothelial tubes assemble in vivo, comparing our results with time-lapse imaging of human endothelial-cell tube formation in three-dimensional collagen matrices in vitro. Our results provide strong support for a model in which the formation and intracellular and intercellular fusion of endothelial vacuoles drives vascular lumen formation."

[5]

Endothelial Progenitors

Recent work has shown that the formation of the initial endothelial tube is by a process of coalescence of cellular vacuoles within the developing endothelial cells, which fuse together without cytoplasmic mixing to form the blood vessel lumen.

[6]

Endothelial Tube Formation

File:Bloodvessel.jpg

Blood Vessel Formation
(Image: Developmental biology: The hole picture Keith Mostov and Fernando Martin-Belmonte Nature 442, 363-364 27 July 2006)

[7] [8]

[9]

[10]

[11]

Stimulators of Angiogenisis (Blood Vessel Growth)

  • Peptide growth factors
    • Vascular endothelial growth factor-Aa,b, -Bb, -Cb, -D
    • [-E], -F (VEGF-Aa,b, -Bb, -Cb, -Db, -E, -F)
    • Placenta growth factor (PlGF)
    • Angiopoietin-1 (Ang-1)
    • Angiopoietin-2 (Ang-2) [modulator in the presence of angiogenic activity]
    • Acidic fibroblast growth factor (FGF-1)
    • Basic fibroblast growth factor (FGF-2)
    • Platelet-derived growth factor (PDGF)
    • Transforming growth factor-a (TGF-a)
    • Transforming growth factor-b (TGF-b)
    • Hepatocyte growth factor (HGF)
    • Insulin-like growth factor-I (IGF-I)
  • Multifunctional cytokines/immune mediators
    • Tumour necrosis factor-a (low-dose)
    • Monocyte chemoattractant protein-1 (MCP-1)
  • CXC-chemokines
    • Interleukin-8 (IL-8)
  • Enzymes
    • Platelet-derived endothelial cell growth factor
    • (PD-ECGF; thymidine phosphorylase)
  • Angiogenin (ribonuclease A homologue)
  • Hormones
    • Oestrogens
    • Prostaglandin-E1, -E2
    • Follistatin
    • Proliferin
  • Oligosaccharides
    • Hyaluronan oligosaccharides
    • Gangliosides

(data from table 1 Vascular morphogenesis in the ovary, Augustin H.G Bailliere's Clinical Obstetrics and Gynaecology 14:867-882, 2000)

Inhibitors of Angiogenisis (Blood Vessel Growth)

  • Peptide growth factors and proteolytic peptides
    • Angiopoietin-2 (Ang-2) [in the absence of angiogenic activity]
    • Angiostatin
    • Endostatin
    • 16 kDa prolactin fragment
    • Laminin peptides
    • Fibronectin peptides
  • Inhibitors of enzymatic activity
    • Tissue metalloproteinase inhibitors
    • (TIMP-1, -2, -3, -4)
    • Plasminogen activator inhibitors
    • (PAI-1, -2)
  • Multifunctional cytokines/immune mediators
    • Tumour necrosis factor-a (high-dose)
    • Interferons
    • Interleukin-12
  • CXC-chemokines
    • Platelet factor-4 (PF-4)
    • Interferon-gamma-inducible protein-10 (IP-10)
    • Gro-beta
  • Extracellular matrix molecules
    • Thrombospondin
  • Hormones/metabolites
    • 2-Methoxyestradiol (2-ME)
    • Proliferin-related protein
  • Oligosaccharides
    • Hyaluronan, high-molecular-weight species

(data from table 1 Vascular morphogenesis in the ovary, Augustin H.G Bailliere's Clinical Obstetrics and Gynaecology 14:867-882, 2000)

Vascular Endothelial Growth Factor

Growing blood vessels follow a gradient generated by tagret tissues/regions of Vascular Endothelial Growth Factor (VEGF) to establish a vascular bed. Recent findings suggest that Notch signaling acts as an inhibitor for this system, preventing sprouting of blood vessels.

Notch is a transmembrane receptor protein involved in regulating cell differentiation in many developing systems.

Links: OMIM - VEGFA | OMIM - Notch

Cardiac Blood Vessels

Earliest vessels in the heart wall develop subepicardially (beneath the outside surface of the heart) near the apex at Carnegie stage 15, which then extends centripetally and at stage 17 coronary arterial stems communicate with the aortic lumen.

(Text modified from: [12])

References

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[TITL+development[WORD]+review[WORD]&doptcmdl=DocSum blood[TITL]+development[WORD]+review[WORD]]

Blood Vessel Development Terms

  • angioblasts stem cells in blood islands generating endothelial cells
  • angiogenesis the formation of blood vessels also called vasculogenesis in the embryo
  • blood islands earliest sites of blood vessel and blood cell formation, seen mainly on yolk sac chorion
  • vascular endothelial growth factor (VEGF) protein growth factor family that stimulates blood vessel growth, a similar factor can be found in the placenta (PIGF).

Glossary Links

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Cite this page: Hill, M.A. (2020, April 9) Embryology Cardiovascular System - Blood Vessel Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Cardiovascular_System_-_Blood_Vessel_Development

What Links Here?
© Dr Mark Hill 2020, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
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