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Hepatology. 2015 Apr;61(4):1406-15. doi: 10.1002/hep.27343. Epub 2015 Mar 9.

Molecular pathophysiology of portal hypertension.

Author information

1
Angiogenesis in Liver Disease Research Group, Institute of Biomedical Research IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain.

Abstract

Over the past two decades the advances in molecular cell biology have led to significant discoveries about the pathophysiology of portal hypertension (PHT). In particular, great progress has been made in the study of the molecular and cellular mechanisms that regulate the increased intrahepatic vascular resistance (IHVR) in cirrhosis. We now know that the increased IHVR is not irreversible, but that both the structural component caused by fibrosis and the active component caused by hepatic sinusoidal constriction can be, at least partially, reversed. Indeed, it is now apparent that the activation of perisinusoidal hepatic stellate cells, which is a key event mediating the augmented IHVR, is regulated by multiple signal transduction pathways that could be potential therapeutic targets for PHT treatment. Furthermore, the complexity of the molecular physiology of PHT can also be appreciated when one considers the complex signals capable of inducing vasodilatation and hyporesponsiveness to vasoconstrictors in the splanchnic vascular bed, with several vasoactive molecules, controlled at multiple levels, working together to mediate these circulatory abnormalities. Added to the complexity is the occurrence of pathological angiogenesis during the course of disease progression, with recent emphasis given to understanding its molecular machinery and regulation. Although much remains to be learned, with the current availability of reagents and new technologies and the exchange of concepts and data among investigators, our knowledge of the molecular basis of PHT will doubtless continue to grow, accelerating the transfer of knowledge generated by basic research to clinical practice. This will hopefully permit a better future for patients with PHT.

PMID:
25092403
DOI:
10.1002/hep.27343
[Indexed for MEDLINE]

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