title: Possible involvement of angiogenesis in chronic liver diseases: interaction among renin-angiotensin-aldosterone system, insulin resistance and oxidative stress.
abstract: 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.
authors.affiliation: Third Department of Internal Medicine, Nara Medical University, Shijo-cho 840, Kashihara, Nara 634-8522, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kaji
authors.forename: H
authors.initials: H
authors.lastname: Yoshiji
authors.forename: Y
authors.initials: Y
authors.lastname: Ikenaka
authors.forename: R
authors.initials: R
authors.lastname: Noguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Aihara
authors.forename: Y
authors.initials: Y
authors.lastname: Shirai
authors.forename: A
authors.initials: A
authors.lastname: Douhara
authors.forename: H
authors.initials: H
authors.lastname: Fukui
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002908:Chronic Disease; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000503:physiopathology* / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors