摘要
This review describes the recent developments in the pathobiology of endothelial dysfunction(ED) in the context of cirrhosis with portal hypertension and defines novel strategies and potential targets for therapy. ED has prognostic implications by predicting unfavourable early hepatic events and mortality in patients with portal hypertension and advanced liver diseases. EDcharacterised by an impaired bioactivity of nitric oxide(NO) within the hepatic circulation and is mainly due to decreased bioavailability of NO and accelerated degradation of NO with reactive oxygen species. Furthermore, elevated inflammatory markers also inhibit NO synthesis and causes ED in cirrhotic liver. Therefore, improvement of NO availability in the hepatic circulation can be beneficial for the improvement of endothelial dysfunction and associated portal hypertension in patients with cirrhosis. Furthermore, therapeutic agents that are identified in increasing NO bioavailability through improvement of hepatic endothelial nitric oxide synthase(e NOS) activity and reduction in hepatic asymmetric dimethylarginine, an endogenous modulator of e NOS and a key mediator of elevated intrahepatic vascular tone in cirrhosis would be interesting therapeutic approaches in patients with endothelial dysfunction and portal hypertension in advanced liver diseases.
This review describes the recent developments in thepathobiology of endothelial dysfunction （ED） in thecontext of cirrhosis with portal hypertension and definesnovel strategies and potential targets for therapy. EDhas prognostic implications by predicting unfavourableearly hepatic events and mortality in patients withportal hypertension and advanced liver diseases. EDcharacterised by an impaired bioactivity of nitric oxide（NO） within the hepatic circulation and is mainly dueto decreased bioavailability of NO and accelerateddegradation of NO with reactive oxygen species.Furthermore, elevated inflammatory markers also inhibitNO synthesis and causes ED in cirrhotic liver. Therefore,improvement of NO availability in the hepatic circulationcan be beneficial for the improvement of endothelialdysfunction and associated portal hypertension inpatients with cirrhosis. Furthermore, therapeutic agentsthat are identified in increasing NO bioavailabilitythrough improvement of hepatic endothelial nitricoxide synthase （eNOS） activity and reduction in hepaticasymmetric dimethylarginine, an endogenous modulatorof eNOS and a key mediator of elevated intrahepaticvascular tone in cirrhosis would be interestingtherapeutic approaches in patients with endothelialdysfunction and portal hypertension in advanced liverdiseases.
基金
Supported by The Department of Biotechnology-Ramalingaswami Fellowship 5 years grant from the Government of India
