Masters Degrees (Medical Physiology)

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Browsing Masters Degrees (Medical Physiology) by browse.metadata.advisor "Dr Genis, Amanda"

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    The vascular and endothelial effects of HIV, antiretroviral therapy and rooibos - functional effects and mechanism
    (Stellenbosch : Stellenbosch University, 2022-12) Molopi, Dintle; Dr Genis, Amanda; Dr Windvogel, Shantal; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Medical Physiology.
    ENGLISH ABSTRACT: Individuals infected with human immunodeficiency virus-1 (HIV-1) are living longer but are at increased risk of cardiovascular disease (CVD). Antiretroviral therapy (ART) has been implicated in the development of CVD in people living with HIV-1, however a gap remains in the mechanisms involved. Rooibos (RB) has been shown to exert potential ameliorative effects against cardiovascular risk factors. Endothelial dysfunction is characterized by reduction of the bioavailability of vasodilators, particularly nitric oxide (NO), and/or an increase in endothelium-derived contracting factors. The aortic-ring model measures optimal contraction/relaxation by measuring isometric-tension (g) as an indication of vasomotor function. Therefore, the aim of this study was to investigate the effects of HIV-1 proteins, ART and rooibos, and a combination thereof on vascular and endothelial function and the possible mechanisms thereof. By evaluating the following objectives: (i) objective 1 to assess vascular reactivity by performing aortic-ring tension studies, utilizing treated thoracic aortas of aged-matched Wistar rats. (ii) Objective 2 To investigate the underlying mechanism involved in endothelial, by assessing the proteins involved in vascular signaling by means of Western blot analysis. Methods Isolated 3-4mm sized aortic rings were incubated for 24 hours with either of the following cocktails: Control (vehicle control), HIV1 (nef, tat & gp160 = 100ng/ml), ART1 (efavirenz = 11.2nM, tenofovir = 1μM and emtricitabine = 2.6µM), ART2 (lopinavir = 20µM and ritonavir = 4µM), RB (2%), HIV1+ART1, HIV1+ART2, HIV1 +RB and HIV1 + ART2 + RB. Thereafter, aortic ring was mounted, and contraction/relaxation reactivity of the vessels were determined in an organ bath perfusion system (AD Instruments, Australia). The remaining tissue of the excised aortas were snap frozen in liquid nitrogen for western blot analysis (n=2-3/group). Results No difference in treatment with HIV1 or ART1 compared to controls were observed. Treatment with ART2 decreased %contraction but had no effect on %relaxation. Treatment with RB decreased %contraction and %relaxation. Co-treatment with HIV1+ART1 decreased %contraction and %relaxation, while HIV1+ART2 decreased %contraction but increased %relaxation. HIV1+ART1 group, HIV1+ART2 group, as well as HIV1+RB group showed decreased %contraction and %relaxation compared to HIV1 only treated aortic rings. HIV1+ART2+RB had no effect on %contraction or %relaxation compared to HIV1. Cleaved-PARP expression was increased in HIV1+ART2 compared to HIV1. Total IκBα expression was increased in HIV1+ART2+RB compared to HIV1 and HIV1+ART2 groups. Conclusion HIV-1 (Nef, Tat and Gp160) had no effect on vasomotor function. While efavirenz, tenofovir and emtricitabine treatment alone had no effect, it had ambiguous effects within this HIV-1 protein environment. Interestingly, lopinavir and ritonavir co-treatment with HIV-1 proteins improved vasomotor function but increased apoptosis. Rooibos caused had an ambiguous effect in aortic reactivity when treated alone, co-treated with HIV1 and had no effect when co-treated with HIV1 and protease inhibitors. However, Rooibos co-treatment with HIV1 and protease inhibitors downregulated the inflammatory NF-κB signaling pathway. Although this study could not pertinently show the harmful effect that HIV-1 proteins and protease inhibitors have on vascular function, the effect of Rooibos in this environment was promising and warrants further investigation into an optimal concentration within this environment.