+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Pulmonary artery adventitial fibroblasts cooperate with vasa vasorum endothelial cells to regulate vasa vasorum neovascularization: a process mediated by hypoxia and endothelin-1



Pulmonary artery adventitial fibroblasts cooperate with vasa vasorum endothelial cells to regulate vasa vasorum neovascularization: a process mediated by hypoxia and endothelin-1



American Journal of Pathology 168(6): 1793-1807



The precise cellular and molecular mechanisms regulating adventitial vasa vasorum neovascularization, which occurs in the pulmonary arterial circulation in response to hypoxia, remain unknown. Here, using a technique to isolate and culture adventitial fibroblasts (AdvFBs) and vasa vasorum endothelial cells (VVECs) from the adventitia of pulmonary arteries, we report that hypoxia-activated pulmonary artery AdvFBs exhibited pro-angiogenic properties and influenced the angiogenic phenotype of VVEC, in a process of cell-cell communication involving endothelin-1 (ET-1). We demonstrated that AdvFBs, either via co-culture or conditioned media, stimulated VVEC proliferation and augmented the self-assembly and integrity of cord-like networks that formed when VVECs where cultured on Matrigel. In addition, hypoxia-activated AdvFBs produced ET-1, suggesting a paracrine role for this pro-angiogenic molecule in these processes. When co-cultured on Matrigel, AdvFBs and VVECs self-assembled into heterotypic cord-like networks, a process augmented by hypoxia but attenuated by either selective endothelin receptor antagonists or oligonucleotides targeting prepro-ET-1 mRNA. From these observations, we propose that hypoxia-activated AdvFBs exhibit pro-angiogenic properties and, as such, communicate with VVECs, in a process involving ET-1, to regulate vasa vasorum neovascularization occurring in the adventitia of pulmonary arteries in response to chronic hypoxia.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 012468341

Download citation: RISBibTeXText

PMID: 16723696

DOI: 10.2353/ajpath.2006.050754


Related references

High proliferative potential endothelial colony-forming cells contribute to hypoxia-induced pulmonary artery vasa vasorum neovascularization. American Journal of Physiology. Lung Cellular and Molecular Physiology 306(7): L661-L671, 2014

Chronic hypoxia impairs extracellular nucleotide metabolism and barrier function in pulmonary artery vasa vasorum endothelial cells. Angiogenesis 14(4): 503-513, 2011

PI3K, Rho, and ROCK play a key role in hypoxia-induced ATP release and ATP-stimulated angiogenic responses in pulmonary artery vasa vasorum endothelial cells. American Journal of Physiology. Lung Cellular and Molecular Physiology 297(5): L954-L964, 2009

Extracellular ATP is a pro-angiogenic factor for pulmonary artery vasa vasorum endothelial cells. Angiogenesis 11(2): 169-182, 2008

Study on the supply of vasa vasorum into tunica media of the common carotid arteries in rabbits and the nutrition of the arterial wall through vasa vasorum. ACTA MED OKAYAMA 16(6 Suppl ): 81-87, 1962

An experimental study on the vascular lesions caused by disturbance of the vasa vasorum. 3. Influence of obstruction of the venous side of the vasa vasorum and the periaortic vein. Japanese Circulation Journal 36(9): 945-951, 1972

Extracellular adenosine triphosphate: a potential regulator of vasa vasorum neovascularization in hypoxia-induced pulmonary vascular remodeling. Chest 128(6 Suppl): 608s-610s, 2005

Hypoxia-Inducible Factor-1/Vascular Endothelial Growth Factor Pathway for Adventitial Vasa Vasorum Formation in Hypertensive Rat Aorta. Hypertension 39(1): 46-50, 2002

Hypoxia-inducible factor-1alpha/vascular endothelial growth factor pathway for adventitial vasa vasorum formation in hypertensive rat aorta. Hypertension 39(1): 46-50, 2002

P2Y1 and P2Y13 purinergic receptors mediate Ca2+ signaling and proliferative responses in pulmonary artery vasa vasorum endothelial cells. American Journal of Physiology. Cell Physiology 300(2): C266-C275, 2011

The influence of sleep apnea syndrome and intermittent hypoxia in carotid adventitial vasa vasorum. Plos one 14(2): E0211742, 2019

Medial Hypoxia and Adventitial Vasa Vasorum Remodeling in Human Ascending Aortic Aneurysm. Frontiers in Cardiovascular Medicine 5: 124, 2018

Detection of adventitial vasa vasorum and intraplaque neovascularization in carotid atherosclerotic lesions with contrast-enhanced ultrasound and their role in atherosclerosis. Methodist Debakey Cardiovascular Journal 7(4): 37-40, 2012

Topologic distributions of vasa vasorum and lymphatic vasa vasorum in the aortic adventitia--Implications for the prevalence of aortic diseases. Atherosclerosis 247: 127-134, 2016

Adventitial microvasculitis or vasa vasorum vasculitis of the temporal artery and systemic diseases. Serratrice, G, Pouget, J, Blin, O, Figarella-Branger, D, Bille-Turc, F, Azulay, J - P, Pellissier, J - F, Advances in Neuromuscular Diseases: Nervous system, muscles and systemic diseases, Actualites Neuromusculaires: System nerveux, muscles et maladies systemiques: 22-27, 1993