Activated pericyte attenuates endothelial functions: nitric oxide-cGMP rescues activated pericyte-associated endothelial dysfunctions.
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.
Majumder
Syamantak
S
Vascular Biology Lab, AU-KBC Research Centre, Anna University, MIT Campus, Chennai, Tamil Nadu, India.
Tamilarasan
K P
KP
Kolluru
Gopi Krishna
GK
Muley
Ajit
A
Nair
C Madhavan
CM
Omanakuttan
Athira
A
Murty
K V G K
KV
Chatterjee
Suvro
S
D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D022081:Cell Surface Extensions / Q000187:drug effects; D002645:Chickens; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D020286:Pericytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D012995:Solubility / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D006152:Cyclic GMP