Effect of Adiponectin Overexpression on Stability of Preexisting Plaques by Inducing Prolyl-4-Hydroxylase Expression

BACKGROUND: Although adiponectin has been implicated as an antiinflammatory factor in atherosclerotic lesion development, little is known about its role in advanced atherosclerotic plaque. This study assessed the effect and mechanism of adiponectin on the expression of prolyl 4-hydroxylase (P4H) alpha1 and its role in the stability of preexisting plaque. METHODS AND RESULTS: Atherosclerotic lesions in the carotid arteries of apolipoprotein E-deficient mice were induced by the placement of a perivascular collar. Six weeks after surgery, 120 mice were divided into phosphate-buffered saline (PBS) (n=40), empty adenovirus (Ad.Empty) (n=40) and adiponectin adenovirus (Ad.Adipo) groups (n=40). The number of vulnerable lesions were lower with Ad.Adipo than with Ad.Empty transfection. Mean cap thickness, cap area, cap-to-core ratio and intimal collagen content were all greater with Ad.Adipo than with Ad.Empty transfection; however, the groups did not differ in plaque area or intima-media thickness. Plasma adiponectin level positively correlated with intimal collagen content. Adiponectin transfection conferred enhanced expression of P4H, with no changes in the PBS and Ad.Empty groups. CONCLUSIONS: Adiponectin increases collagen production by inducing the expression of P4H, which may play a major role in the development of the thick fibrous cap of advanced atherosclerotic plaque.