Perivascular Mast Cells Promote Atherogenesis and Induce Plaque Destabilization in Apolipoprotein E–Deficient Mice

Abstract

Background-Mast cells are major effector cells in allergy and host defense responses. Their increased number and state of activation in perivascular tissue during atherosclerosis may point to a role in cardiovascular disorders. In the present study, we investigated the contribution of perivascular mast cells to atherogenesis and plaque stability in apolipoprotein E-deficient mice. Methods and Results-We show here that episodes of systemic mast cell activation during plaque progression in mice leads to robust plaque expansion. Targeted activation of perivascular mast cells in advanced plaques sharply increases the incidence of intraplaque hemorrhage, macrophage apoptosis, vascular leakage, and CXCR2/VLA-4 -mediated recruitment of leukocytes to the plaque. Importantly, treatment with the mast cell stabilizer cromolyn does prevent all the adverse phenomena elicited by mast cell activation. Conclusions-This is the first study to demonstrate that mast cells play a crucial role in plaque progression and destabilization in vivo. We propose that mast cell stabilization could be a new therapeutic approach to the prevention of acute coronary syndromes.

Galectin-3 Gene Inactivation Reduces Atherosclerotic Lesions and Adventitial Inflammation in ApoE-Deficient Mice

“…54 The importance of perivascular mast cell activation in plaque progression and destabilization has been demonstrated in ApoE-deficient mice. 55 Our study has shown the extent of mast cell involvement in the perivascular inflammatory response, and this mechanism may have significant clinical consequences.…”

Enhanced Inflammation in Epicardial Fat in Patients With Coronary Artery Disease

“…1,2) It was demonstrated that perivascular adventitial adipose tissue releases a transferable adventitia-derived relaxing factor that acts by tyrosine kinase-dependent activation of K + channels in vascular smooth muscle cells. 3) Recent reports showed that periadventitial fat secretes various chemokines that might contribute to the progression of obesity-associated atherosclerosis.…”

Stimulated mast cells promote maturation of myocardial microvascular endothelial cell neovessels by modulating the angiopoietin-Tie-2 signaling pathway

“…However, the new blood vessels induced by MCs display many structural and functional abnormalities (4,5). Paradoxically, enhanced migration, proliferation, and capillary-like tube formation of MMVECs induced by MCGs also show an interrupted vessel maturation process.…”

“…These cells are topographically associated with small vessels and accumulate during angiogenesis and different pathological processes, including atherosclerosis, hemangioma, and tumor growth (2,3). However, these new blood vessels display many structural and functional abnormalities, with no recognizable features of arterioles, capillaries, and venules, due to lack of normal vessel hierarchy (4,5), and they are thus prone to hemorrhage.…”