title: Hepatocyte growth factor promotes an anti-inflammatory cytokine profile in human abdominal aortic aneurysm tissue.
abstract: Abdominal aortic aneurysm (AAA) is characterized by the destruction of tissue architecture due to chronic inflammation of unknown etiology. Recent studies have indicated that control of inflammation is a promising therapeutic strategy; however, no established pharmacological intervention is currently available for AAA. We found that hepatocyte growth factor (HGF) was expressed in aneurysmal tissue, and colocalized with von Willebrand factor, the endothelial cell marker, in the most damaged part of the aneurysmal walls. In ex vivo cultures of human AAA tissue, exogenously added HGF in the presence of tumor necrosis factor-alpha (TNF-α) enhanced the secretion of anti-inflammatory cytokine interleukin-10 (IL-10) and suppressed the secretion of proinflammatory monocyte/macrophage chemotactic protein-1 (MCP-1). The angiotensin converting enzyme (ACE) inhibitors, imidaprilat and perindoprilat, enhanced the secretion of endogenous HGF, augmented the TNF-α-induced IL-10 secretion and suppressed MCP-1 secretion from AAA tissue. The ACE inhibitors also augmented the expression of HGF in the presence of bradykinin in human aortic endothelial cells in culture (HAECs). In contrast, HGF secretion was not affected by either an angiotensin II type 1 receptor (AT1) antagonist or angiotensin II in AAA tissue or in HAECs. These results suggested that angiotensin converting enzyme inhibitors may be useful in controlling chronic inflammation in AAA, partly due to their enhancement of HGF secretion.
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shintani
authors.forename: Hiroki
authors.initials: H
authors.lastname: Aoki
authors.forename: Michihide
authors.initials: M
authors.lastname: Nishihara
authors.forename: Satoko
authors.initials: S
authors.lastname: Ohno
authors.forename: Aya
authors.initials: A
authors.lastname: Furusho
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Hiromatsu
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Akashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Aoyagi
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology*; D001011:Aorta / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D048289:Imidazolidines / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D012084:Renin-Angiotensin System; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D048289:Imidazolidines; D007211:Indoles; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C053500:perindoprilat; D017228:Hepatocyte Growth Factor; C078006:imidaprilat