Anti-inflammatory and immune-modulatory therapies for preventing atherosclerotic cardiovascular disease.

Atherosclerosis is believed to be a chronic inflammation of the arterial wall and various immune cells of innate and adaptive immunity involves in the pathogenesis of atherosclerosis. Based on this notion, several anti-inflammatory strategies for prevention of atherosclerosis have been examined mainly using animal models. Vaccination or mucosal immunization with athero-antigens comes under candidate therapeutic methods for antigen-specific prevention of atherosclerosis. Immune suppression mediated by regulatory T cells (Tregs) could be another method to regulate pathogenic chronic inflammation in atherogenesis. Inducible Tregs are reported to differentiate peripherally in the intestine and we have been interested in the oral tolerance, in which not only Tregs but also tolerogenic dendritic cells play crucial roles. We demonstrated that modulation of the intestinal immunity including oral tolerance could be a novel therapy against atherosclerosis. Further, downregulation of effector T cell response and/or Treg predominant condition was shown to induce atherosclerosis regression and inhibit the progression of aneurysm. In clinical situations, none of the approaches to specifically and directly treat inflammation to prevent cardiovascular events or reduce atherosclerosis in human individuals were successful, although high-sensitive C-reactive protein is shown to have a strong relationship with recurrent events of cardiovascular diseases in several randomized clinical trials. Now two randomized placebo-controlled clinical trials evaluating anti-inflammatory agents are being conducted in the USA and Canada to clarify whether targeting the inflammation itself will reduce cardiovascular events and risks. In this review, we present the current understanding of anti-inflammatory and immune-modulation therapies against atherosclerosis and discuss the future perspectives.