The Role of Mast Cells in Acute Coronary Syndromes

OBJECTIVE:Review evidence supporting the role of mast cells in cardiovascular pathophysiology. BACKGROUND: Cardiovascular inflammation has emerged as a key pathogenetic factor in coronary artery disease (CAD) and myocardial ischemia reperfusion (IR) injury. IR complicates all forms of coronary artery revascularization. Cardiac mast cells have been implicated in CAD, IR and myocardial infarction (MI) through the release of pro-arrhythmogenic and inflammatory mediators, especially interleukin-6 (IL-6), considered an independent risk factor. METHODS:We reviewed relevant literature and summarized our own findings. RESULTS: We showed that CAD is associated with high intracoronary release of IL-6. Acute stress triggers mast cell- dependent release of histamine and IL-6. Moreover, acute stress in ApoE -/- mice leads to ischemia. Mast cells express corticotropin-releasing-hormone (CRH) receptors, activation of which leads to selective release of vascular endothelial growth factor (VEGF), an isoform of which is vasodilatory. In a randomized prospective study, we investigated serum IL-6 levels and cardiac tissue susceptibility in the mast cell deficient (W/Wv) mice (n=12) and their normal littermates (+/+). When the left coronary artery (LCA) was ligated followed by 6 hr of reperfusion IL-6 levels increased significantly after reperfusion only in the +/+ mice, but not in mast cell deficient W/Wv mice; cardiac muscle viability was significantly higher in W/Wv than the +/+ mice. CONCLUSION: These results support targeting selective inhibition of cardiac mast cell activation as prophylactic therapy in clinical situations involving myocardial inflammation and/or revascularization