Effects of immunomodulators on cardiovascular disease

Abstract

Cardiovascular disease (CVD) is a genetic and environmental factors involved disease resulting in cardiovascular dysfunction. This study investigated cardiovascular dysfunction induced by immunomodulators including methamphetamine (MA), high salt-fat dietary and retrovirus. The mechanism and potential therapeutic role of T-cell receptor (TCR) peptides in cardiovascular disease were studied. The immune and cardiac function changes due to chronic MA use were evaluated in C57BL/C mice with LP-BM5 retrovirus infection plus MA intraperitoneally injection for 12 weeks. MA treatment significantly decreased T helper 1 (TH1) cytokine production; tumor necrosis factor (TNF-α) and oxidative stress were significantly increased in both uninfected and infected mice; the load independent contractile cardiac function was significantly decreased. The poor dietary intake effects on cardiovascular function were investigated in one-month old C57BL/6J mice fed with two established dietary formulations, high salt (HS) and high fat-high carbohydrate (HFHSC), separately or in combination (HFHS) for 3 months. The HFHSC mice demonstrated significantly increased end-diastolic volume and end-systolic volume (p < 0.01) and a reduction of ventricular stiffness (p < 0.05). The HS mice exhibited arterial hypertension with an increase in maximum end-systolic pressure (p < 0.05) and a decrease of arterial elastance (p < 0.05) corroborated by an increase in heart weight to body weight ratios (p < 0.01) and vascular types I and III collagen. Modulated T-lymphocyte function with a suppressed TH2 subset fashion by TCR peptide vaccination significantly increased collagen I and III mRNA and protein in cardiac cells from naive mice (p < 0.05). The gelatinase MMP-2 and collagenase MMP-13 mRNA expression were significantly decreased (p < 0.05). Meanwhile, the compliance of heart (β and dV/dt min) was significantly increased by T-cell receptor peptide treatment (p < 0.05). LP-BM5 retrovirus-infection induced DCM was improved by TCR peptide treatment. The collagen I & III mRNA and protein levels were significantly increased by TCR peptide treatment in both fibroblast and cardiac cells (p < 0.05). In conclusion, drug use, poor dietary intake and retrovirus-infection as immunomodulation factors induce cardiovascular dysfunction mediated by T-lymphocyte dysregulation. TCR peptide, a selective T-lymphocyte function modulator, may be a promising pharmaco-therapeutic immunomodulator for cardiovascular disease.