AdvisorLarson, Douglas F.
Watson, Ronald R.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractCardiovascular 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.
Degree ProgramGraduate College