A hypothesis: adiponectin mediates anti-atherosclerosis via adventitia-AMPK-iNOS pathway.
Adiponectin is an adipocyte-derived protein with insulin-sensitizing, anti-inflammatory, and anti-atherogenic properties and is abundantly found in plasma. Vascular adventitia is the outermost connective and supporting tissue of vessels. Recently, increasing evidence has shown that infection in the adventitia is one of the causes of atherosclerosis and restenosis. Our previous study indicated that local transferring adenovirus expressing adiponectin gene (Ad-APN) to intima and adventitia can suppress atherosclerosis, but the exact mechanism is still obscure. We speculate that with infection in the adventitia, adiponectin can activate AMP-activated protein kinase (AMPK) through adiponectin receptors in the membranes of adventitial fibroblasts and then inhibit the expression and activity of inducible nitric oxide synthase (iNOS); secretion of adventitial infective factors; division, proliferation and translation of adventitial fibroblasts; and change of adventitial fibroblasts to myofibroblasts, finally decreasing oxidative/nitrative stress to reduce atherosclerotic plaque area and stabilize atherosclerotic plaques. The proposition may provide clues into the development of a novel treatment for atherosclerosis.
Cai
Xiao-jun
XJ
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong 250012, China.
Li
Chang-jiang
CJ
Chen
Liang
L
Rong
Yuan-yuan
YY
Zhang
Yun
Y
Zhang
Mei
M
D000263:Adenylate Kinase / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism*; D000273:Adipose Tissue; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D002318:Cardiovascular Diseases / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008962:Models, Theoretical; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*
D052242:Adiponectin; D000893:Anti-Inflammatory Agents; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D000263:Adenylate Kinase