Activated pericyte attenuates endothelial functions: nitric oxide – cGMP rescues activated pericyte-associated endothelial dysfunctions

Abstract

Hepatic stellate cells are liver-specific pericytes and exist in close proximity with endothelial cells. The activation of liver pericytes is intrinsic to liver pathogenesis, and leads to endothelial dysfunction, including the low bioavailability of nitric oxide (NO). However, the role of nitric oxide in pericyte-endothelium cross-talk has not yet been elucidated. This work examines the cellular mechanism of action of NO in pericyte-mediated endothelial dysfunction. We used in vitro coculture and conditioned medium systems to study the effects of activated liver pericytes on endothelial function, and an egg yolk vascular bed model was used to study the effects of activated pericytes on angiogenesis. This study also demonstrates that activated pericytes attenuate the migration, proliferation, permeability, and NO production of endothelial cells. Our results demonstrate that activated pericytes restrict angiogenesis in egg yolk vascular bed models, and NO supplementation recovers 70% of the inhibition. Our results also demonstrate that supplementation with NO, sildenafil citrate (phosphodiesterase inhibitor), and 8-bromo-cGMP (cGMP analog) partially recovers activated-pericyte-mediated endothelium dysfunction. We conclude that NO-cGMP alleviates activated-pericyte-associated endothelial dysfunction, including angiogenesis, in a cGMP-dependent manner.

Thalidomide attenuates nitric oxide‐driven angiogenesis by interacting with soluble guanylyl cyclase

“…, 2004), the cells were washed with PBS and incubated with thalidomide for 8 h. Bright field images were taken with 4× magnifications under an inverted microscope. To study the cross talk between thalidomide and the NO downstream pathway, we used 50 µM 1H‐[1,2,4]‐oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) (concentration from Majumder et al. , 2007; Kolluru et al.…”

“…, 2008); a haem site inhibitor of soluble guanylyl cyclase (sGC); and 10 µM LY83583 (concentration from Millette and Lamontagne, 1996), a reversible inhibitor of sGC. Further, to evaluate the effects of external cGMP administration on thalidomide‐treated cells, we incubated ECs with 50 µM 8Br‐cGMP (concentration from Majumder et al. , 2007; Kolluru et al.…”

“…, 2007; Kolluru et al. , 2008), an analogue of cGMP, and 10 µM sildenafil citrate (SC; concentration from Majumder et al. , 2007; Kolluru et al.…”

“…Ring formation experiments were performed using the protocol mentioned elsewhere (Majumder et al. , 2007).…”

Protection of retinal vasculature by losartan against apoptosis and vasculopathy in rats with spontaneous hypertension

“…The retinal capillaries are known to contain endothelial cells and pericytes. The pericytes may function as a progenitor of endothelial cells or accessory cells that support the regeneration and repair of the blood vessel network [12,13]. Obviously, both endothelial cells and pericytes are important for maintaining the stability and integrity of retinal vasculature.…”