Possible Involvement of Angiogenesis in Chronic Liver Diseases: Interaction Among Renin-Angiotensin-Aldosterone System, Insulin Resistance and Oxidative Stress
2012
Angiogenesis plays a pivotal role in many pathological processes including chronic liver diseases. Various factors, such as
renin-angiotensin-aldosterone system (RAAS), insulin resistance (IR), and reactive oxygen species (ROS) contribute reciprocally to
promote angiogenesis. Blockade of RAAS by angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II (AngII) receptor
blocker (ARB) markedly attenuates liver fibrosis and hepatocellular carcinoma (HCC) along with suppression of angiogenesis, IR, and
ROS. Aldosterone (Ald), a downstream component of AngII, is also involved in these processes, and a selective Ald blocker (SAB)
significantly suppressed the progression of chronic liver diseases. The IR status itself has shown to directly accelerate the progression of
chronic liver diseases whereas inhibition of ROS by iron chelator suppressed it through augmentation and inhibition of
neovascularization. The combination therapy of ACE-I/ARB/SAB with other clinically used agents, such as interferon, imatinib
mesylate, vitamin K, iron chelator, and branched-chain amino acids (BCAA) exerted more potent inhibitory effects on the development
of liver fibrosis and HCC than the treatment using a single agent alone. Collectively, the anti-angiogenic treatment targeting RAAS, IR,
ROS with clinically available agents may become a new therapeutic strategy against the progression of chronic liver diseases.
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