New concepts in the pathogenesis of portal hypertension: hepatic wounding and stellate cell contractility.
The pathogenesis of portal hypertension is multifactorial, and appears to result from interplay between fixed and dynamically modulable elements; the stellate cell is a newly recognized example of the latter. This perisinusoidal, pericyte-like cell has contractile features that are most prominent after liver injury, concomitant with their activation. These data imply an exaggerated contractile phenotype in the cirrhotic liver. This cell may contribute to increased intrahepatic portal hypertension via perisinusoidal constriction of the sinusoid or by contraction of fibrous extracellular matrix rich in type I collagen with concomitant disruption of lobular architecture. Endothelins and NO play a major role in the modulation of stellate cell contractility, and are therefore important in the pathogenesis of intrahepatic portal hypertension. These new data provide potential areas for therapeutic intervention in this clinical entity.
Rockey
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DC
Gastroenterology Division, Duke University Medical Center, Durham, North Carolina 27710, USA.
D002248:Carbon Monoxide; D016232:Endothelins / Q000502:physiology; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D006975:Hypertension, Portal / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D008102:Liver Circulation / Q000502:physiology; D008103:Liver Cirrhosis / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D008833:Microcirculation / Q000502:physiology; D009569:Nitric Oxide; D017466:Receptors, Endothelin / Q000502:physiology
D016232:Endothelins; D017466:Receptors, Endothelin; D009569:Nitric Oxide; D002248:Carbon Monoxide