Myocardial proinflammatory cytokine expression and left ventricular remodeling in patients with chronic mitral regurgitation

Article

关键词: TUMOR-NECROSIS-FACTOR;    ELEVATED CIRCULATING LEVELS;    ADULT FELINE MYOCARDIUM;    CHRONIC HEART-FAILURE;    FACTOR-ALPHA GENE;    TRANSGENIC MICE;    MATRIX METALLOPROTEINASES;    PROTEIN EXPRESSION;    FACTOR RECEPTORS;    CARDIOMYOPATHY;   

DOI  :  10.1161/01.CIR.0000049745.38594.6D

来源: SCIE

【 摘 要 】

Background-In an animal model, stretch was shown to induce myocardial tumor necrosis factor-alpha (TNF-alpha) expression. The purposes of this study were to determine whether the left ventricular (LV) volume overload that occurs in patients with chronic mitral regurgitation (MR) can induce myocardial and systemic TNF-alpha expression and whether there is a relationship between TNF-alpha expression and LV remodeling. Methods and Results-Plasma TNF-alpha and its receptors were measured before mitral valve (MV) repair surgery in 26 MR patients and 23+/-12 months after MV repair surgery in 9 MR patients. Myocardial mRNA copies of TNF-alpha were determined in 11 MR and 10 donor hearts using quantitative RT-PCR. Compared with 15 control subjects, pre-MV repair plasma TNF-alpha (3.59+/-1.81 versus 2.03+/-1.02 pg/mL, P<0.005) and its receptor levels were elevated in MR patients. Myocardial TNF-α mRNA copies (corrected for β-actin mRNA expression) in MR patients and donor hearts were 38.96+/-42.74x10(6) and 0.88+/-0.75x10(6), respectively (P=0.01). After MV surgery, there was a decrease in the plasma levels of TNF-α (2.79+/-1.14 versus 3.51+/-1.34 pg/mL, P=0.02) and its receptors. There was a correlation between myocardial TNF-α expression and preoperative LV end-diastolic and end-systolic volumes. Moreover, there was an inverse correlation between myocardial TNF-α expression and regression in LV end-diastolic (r= -0.76, P=0.007) and end-systolic (r= -0.73, P=0.01) volumes after MV surgery. Conclusions-TNF-α is expressed in the myocardium and plasma of MR patients. Correction of the LV volume overload with MV surgery results in reversal of TNF-α expression. There is a relationship between TNF-α expression and parameters of LV remodeling, suggesting that TNF-α may play a role in the pathogenesis of the LV remodeling that occurs in MR.

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