Abstract
Atherosclerosis is now considered an inflammatory disease, representing the paradigm shift over the last several decades. More intriguing recent data suggest that human inflammatory vasculopathy can by triggered by infectious agents. Even minor infections such as gingivitis have been linked to accelerated vascular disease, while profoundly inflammatory disorders such as rheumatoid arthritis have shown a propensity to increased vascular complications. Human mast cells are often found perivascularly and at mucosal sites and and are of pivotal importance to host defense and the inflammatory response. Recent studies demonstrate that mast cells also play roles in the genesis of atherosclerotic vascular disease. Mast cells express toll-like receptors (TLRs) and also express other cell surface receptors such as the receptor for interleukin-1 (IL-1r). Interactions between bacterial pathogens and mast cell TLR and/or related receptors can lead to the elaboration of inflammatory cytokines. These can recruit/activate other inflammatory cells that further accelerate interactions with adaptive immunity (T and B cells). The elaboration of IL-6 by mast cells can contribute to the hepatic production of C reactive protein (CRP), an established biomarker for atherosclerosis. The elaboration of IL-1from the mast cell (autocrine) or from adventitial cells (paracrine) can lead to further mast cell activation, resulting in an inflammatory loop characterized by further endocrine IL-6 and inflammatory cytokine production, with resultant recruitment and/or activation of other inflammatory cell types and progression of inflammatory vasculopathy. These effects may be mediated by mast cell expression of nuclear factor kappaB and mitogen activated protein kinases (MAPK). Inhibition of mast cell activation and mediator synthesis may play adjunctive futuristic roles in the management of cardiovascular disease.