Involvement of Polyamines From Cardiac Mast Cells in Myocardial Remodeling Induced by Pressure Overload Through Mitochondrial Permeability Transition Pore Opening

Abstract

Objective: Polyamines mainly contain spermine (SPM), spermidine (SPD), and putrescine (PUT). Many research results suggest that polyamines participate in cell proliferation, differentiation, and the regulation of gene expression, and have a close relationship with the occurrence and development of many diseases. However, the role and possible mechanisms of action of polyamines from cardiac mast cells in myocardial remodeling induced by pressure overload remain to be elucidated. Methods: Pressure overload was induced by abdominal aortic constriction (AAC). Toluidine blue staining was used to visualize mast cells in cardiac tissue. The polyamine content of cardiac tissue was analyzed using high-performance liquid chromatography. Opening of the mitochondrial permeability transition pore (MPTP) was determined by the Ca2+-induced swelling of isolated cardiac mitochondria, measured as a reduction in A520. Results: Compared with sham rats, the cardiac mast cell density, the polyamine content (PUT, SPB, and SPM), and myocardial MPTP opening in rats with AAC were significantly increased (P < 0.05), and were accompanied by increased myocardial fibrosis and heart weight/body weight ratio. Intraperitoneal injection of polyamines mimicked these results, and these effects were reversed by cromolyn sodium, a mast cell stabilizer (P < 0.05). Myocardial MPTP opening increased in rats with AAC (P < 0.05), and the three polyamines also increased myocardial MPTP opening (P < 0.05). Conclusion: Mast cell-derived polyamines are involved in pressure overload-induced myocardial remodeling by increasing opening of the MPTP.