TY  - JOUR
A1  - Iwakiri, Yasuko
A1  - Trebicka, Jonel
T1  - Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy
T2  - JHEP reports
N2  - Portal hypertension, defined as increased pressure in the portal vein, develops as a consequence of increased intrahepatic vascular resistance due to the dysregulation of liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), frequently arising from chronic liver diseases. Extrahepatic haemodynamic changes contribute to the aggravation of portal hypertension. The pathogenic complexity of portal hypertension and the unsuccessful translation of preclinical studies have impeded the development of effective therapeutics for patients with cirrhosis, while counteracting hepatic and extrahepatic mechanisms also pose a major obstacle to effective treatment. In this review article, we will discuss the following topics: i) cellular and molecular mechanisms of portal hypertension, focusing on dysregulation of LSECs, HSCs and hepatic microvascular thrombosis, as well as changes in the extrahepatic vasculature, since these are the major contributors to portal hypertension; ii) translational/clinical advances in our knowledge of portal hypertension; and iii) future directions.
KW  - HSC
KW  - LSEC
KW  - fibrosis
KW  - angiogenesis
KW  - liver stiffness
KW  - Rho-kinase
KW  - NO
KW  - FXR
KW  - VEGF
KW  - statins
KW  - NSBB
KW  - TIPS
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63083
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-630837
SN  - 2589-5559
N1  - NIH grants (R01DK117597, 1R01AA025342 and R56DK121511) to YI and Deutsche Forschungsgemeinschaft (SFB TRR57 to P18, CRC 1382 to A09), European Union's Horizon 2020 Research and Innovation Programme (Galaxy, No. 668031; MICROB-PREDICT, No. 825694; DECISION, No. 847949), Eurostars (DeFiber, E!12350), IK and Societal Challenges - Health, Demographic Change and Wellbeing (LIVERHOPE, No. 731875), and Cellex Foundation (PREDICT) to JT.
VL  - 3.2021
IS  - 4, art. 100316
SP  - 1
EP  - 14
PB  - Elsevier
CY  - Amsterdam
ER  -