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This contributes to an increased vascular resistance in the intrahepatic\/sinusoidal microcirculation and develops portal hypertension. Portal hypertension, in turn, causes endothelial dysfunction in the extrahepatic, i.e. splanchnic and systemic, circulation. Unlike dysfunction in LSECs, endothelial dysfunction in the splanchnic and systemic circulation causes overproduction of vasodilator molecules, leading to arterial vasodilation. In addition, portal hypertension leads to the formation of portosystemic collateral vessels. Both arterial vasodilation and portosystemic collateral vessel formation exacerbate portal hypertension by increasing the blood flow through the portal vein. Pathological consequences, such as oesophageal varices and ascites, result. While the sequence of pathological vascular events in cirrhosis and portal hypertension has been elucidated, the underlying cellular and molecular mechanisms causing endothelial dysfunctions are not yet fully understood. This review article summarizes the current cellular and molecular studies on endothelial dysfunctions found during the development of cirrhosis and portal hypertension with a focus on the intra\u2010 and extrahepatic circulations. The article ends by discussing the future directions of the study for endothelial dysfunction.<\/jats:p>","DOI":"10.1111\/j.1478-3231.2011.02579.x","type":"journal-article","created":{"date-parts":[[2011,7,6]],"date-time":"2011-07-06T03:48:40Z","timestamp":1309924120000},"page":"199-213","source":"Crossref","is-referenced-by-count":176,"title":["Endothelial dysfunction in the regulation of cirrhosis and portal hypertension"],"prefix":"10.1111","volume":"32","author":[{"given":"Yasuko","family":"Iwakiri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,7,5]]},"reference":[{"issue":"3","key":"e_1_2_7_2_2","first-page":"S247","article-title":"Vascular deterioration in cirrhosis","volume":"41","author":"Bosch J.","year":"2007","journal-title":"the big picture"},{"issue":"1","key":"e_1_2_7_3_2","first-page":"S121","article-title":"The hyperdynamic circulation of chronic liver 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