Hypercapnia prevents neovascularization via nitrative stress.

Daniella Checchin (1, 2) , Florian Sennlaub (1, 3) , Mirna Sirinyan (1, 2) , Sonia Brault (1, 2) , Tang Zhu (1) , Elsa Kermorvant-Duchemin (1) , Pierre Hardy (1) , Michael Balazy (4) , Sylvain Chemtob (1, 2)

1 Departments of Pediatrics, Ophthalmology, and Pharmacology
2 Department of Pharmacology and Therapeutics [Montréal]
3 Physiopathologie des Maladies Oculaires : Innovations Therapeutiques
4 Department of Pharmacology

Neovascularization after an ischemic insult is a beneficial attempt to salvage the injured tissue. Yet, despite the production of angiogenic factors within ischemic tissues, compensatory growth of new vessels fails to provide adequate vascularization. Thus, we hypothesized that local factors counter efficient revascularization. Whereas ischemia is often considered to be synonymous with an oxygen deficit, it is also associated with a concomitant local elevation of carbon dioxide (CO2). Although studies suggest that hypercapnia impacts tissue neovascularization, its significance relative to the abundantly described effects of hypoxia and its underlying mechanisms have yet to be elucidated. Therefore, we investigated the effects of hypercapnia on blood vessel growth in models of developmental and ischemic neovascularization. Acute and prolonged CO2 exposure inhibited developmental neovascularization of the rodent retina, as well as revascularization of the ischemic retina. Hypercapnia induced early increases in endothelial nitric oxide synthase and nitrative stress, associated with astrocyte impairment and endothelial cell death, as well as downregulation of the proangiogenic prostaglandin E2 receptor EP3. These results establish a previously unexplored means by which hypercapnia hinders efficient neovascularization, a mechanism that may contribute to ischemic tissue injury.

Domains: Neurons and Cognition [q-bio.NC]

Daniella Checchin, Florian Sennlaub, Mirna Sirinyan, Sonia Brault, Tang Zhu, et al.. Hypercapnia prevents neovascularization via nitrative stress.. Free Radical Biology and Medicine, 2006, 40 (3), pp.543-53. ⟨10.1016/j.freeradbiomed.2005.09.016⟩. ⟨inserm-00150827⟩