Local adiponectin treatment reduces atherosclerotic plaque size in rabbits

Abstract

In this study, we investigated the in vivo role of adiponectin, an adipocytokine, on the development of atherosclerosis in rabbits mainly using adenovirus expressing adiponectin gene (Ad-APN) and intravascular ultrasonography. Serum adiponectin concentrations in rabbits after Ad-APN local transfer to abdominal aortas increased about nine times as much as those before transfer (P!0 . 01), about ten times as much as the levels of endogenous adiponectin in adenovirus expressing b-galactosidase gene (Ad-bgal) treated rabbits (P!0 . 01), and about four times as much as those in the aorta of non-injured rabbits on a normal cholesterol diet (P!0 . 01). Ultrasonography revealed a significantly reduced atherosclerotic plaque area in abdominal aortas of rabbits infected through intima with Ad-APN, by 35 . 2% compared with the area before treatment (P!0 . 01), and by 35 . 8% compared with that in Ad-bgal-treated rabbits (P!0 . 01). In rabbits infected through adventitia, Ad-APN treatment reduced plaque area by 28 . 9% as compared with the area before treatment (P!0 . 01) and 25 . 6% compared with that in Ad-bgal-treated rabbits (P!0 . 01). Adiponectin significantly suppressed the mRNA expression of vascular cell adhesion molecule-1 (VCAM-1) by 18 . 5% through intima transfer (P!0 . 05) and 26 . 9% through adventitia transfer (P!0 . 01), and intercellular adhesion molecule-1 (ICAM-1) by 40 . 7% through intima transfer (P!0 . 01), and 30 . 7% through adventitia transfer (P!0 . 01). However, adiponectin had no effect on the expression of types I and III collagen. These results suggest that local adiponectin treatment suppresses the development of atherosclerosis in vivo in part by attenuating the expression of VCAM-1 and ICAM-1 in vascular walls.

Effect of Atorvastatin Versus Rosuvastatin on Levels of Serum Lipids, Inflammatory Markers and Adiponectin in Patients with Hypercholesterolemia

“…The adipocytokine adiponectin is highly specific for adipose tissue. It improves insulin resistance, regulates lipid metabolism such as stimulating fatty-acid oxidation and has anti-inflammatory properties (33)(34)(35)(36), considered independent risk factors for cardiovascular disease (37). In the vascular endothelium, adiponectin decreases monocyte adhesion to endothelium, suppresses macrophage-to-foam cell transformation, and inhibits vascular smooth muscle cell proliferation and migration (3).…”

Adiponectin and end-stage renal disease

“…It suppresses macrophageto-foam cell transformation and retards human aortic smooth muscle cell proliferation, while local injection into atherosclerotic plaque reduces the development of atherosclerosis by attenuating the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in vessel walls. [76][77][78] The vascularprotective activities of adiponectin have been attributed to the HMW isoform. 79 In spite of the cardioprotective properties attributed to adiponectin, cardiovascular complications remain the main cause of mortality in the ESRD population.…”

Anti-inflammatory mediators for molecular imaging of atherosclerosis

“…Adiponectin is thought to protect against diabetes and AS (11,82,83,(85)(86)(87)(88). Li et al showed that local treatment with adiponectin reduces atherosclerotic plaque size in rabbits by decreasing the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in the vascular walls (89). Recently, Okamoto et al found that adiponectin reduces the thrombogenic potential of macrophages by inhibiting tissue factor expression and activity (90).…”