Deficiency of the Long Pentraxin PTX3 Promotes Vascular Inflammation and Atherosclerosis

Abstract

Background— Immune responses participate in several phases of atherosclerosis; there is, in fact, increasing evidence that both adaptive immunity and innate immunity tightly regulate atherogenesis. Pentraxins are a superfamily of acute-phase proteins that includes short pentraxins such as C-reactive protein or long pentraxins such as PTX3, a molecule acting as the humoral arm of innate immunity. To address the potential role of PTX3 in atherogenesis, we first investigated the expression of PTX3 during atherogenesis, generated double-knockout mice lacking PTX3 and apolipoprotein E, and then studied the effect of murine PTX3 deficiency on plasma lipids, atherosclerosis development, and gene expression pattern in the vascular wall. Methods and Results— PTX3 expression increases in the vascular wall of apolipoprotein E–knockout mice from 3 up to 18 months of age. Double-knockout mice lacking PTX3 and apolipoprotein E were fed an atherogenic diet for 16 weeks. Aortic lesions were significantly increased in dou...