Browsing by Author "Everson, Frans Pieter"
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- ItemHIV/AIDS and air pollution as emerging cardiovascular risk factors in Cape Town populations : is endothelial function a marker of effect(Stellenbosch : Stellenbosch University, 2020-03) Everson, Frans Pieter; Strijdom, Hans; De Boever, P.; Nawrot, T. S.; Goswami, N.; Stellenbosch University. Faculty of Medical Sciences. Dept of Biomedical Sciences: Medical Physiology.ENGLISH ABSTRACT: Background: HIV and antiretroviral therapy (ART) are associated with cardiovascular disease (CVD). Concomitantly,air pollution is a global health concern and associated with CVD. Although South Africa (SA) has the largest HIV population, ART roll-out programme and also one of the most carbon-intensive economies in world, the effects of these emerging cardiovascular risk factors remain under investigated. Aim: The current study aimed to investigate whether endothelial function (an early marker of cardiovascular risk/disease) is a marker of effect of HIV, ART and air pollution in a study cohort residing in the Cape Town region. Methods: Volunteering participants were recruited from health-care clinics in Worcester and Cape Town. A health questionnaire was completed (demographic, lifestyle, and socioeconomic information), anthropometric measurements taken (BMI and blood pressure) and fasting blood and urine samples collected from each participant for chemical pathology and biomarker analyses. Sub-study 1 followed a repeated measures design (baseline and 18-month follow-up visit) to investigate the effects of HIV (viral load) and ART (pre- vs. post-ART treatment and an 18-month ART treatment period) on markers of endothelial function. Sub-study 2 investigated the effects of personal air pollution exposure (NO2 and BTEX via passive diffusion samplers) in a repeated measures design (baseline and 6-month follow-up visit) on markers of endothelial function. Markers of endothelial function for both sub-studies included: tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1),vascular cellular adhesion molecule-1 (VCAM-1), e-selectin, p-selectin, vascular endothelial growth factor (VEGF), plasminogen activator inhibitor-1 (PAI-1), retinalmicrovascular calibres (including central retinal arteriolar/venular equivalent (CRAE; CRVE), CRAE/CRVE ratio (AVR)) and flow-mediated dilation (FMD). Results: Sub-study 1: Each interquartile range (IQR) increment increase in viral load (1300 copies mRNA/ml) was associated with CRVE (9.29 μm), AVR (-0.016) and %FMD (-2.13%). Compared to baseline, initiating ART was associated with VCAM-1 (-148 ng/ml), VEGF (40.6%), PAI-1 (14.12 ng/ml) and CRVE (-6.42 μm). An 18-month ART treatment period was associated with TNF-α (-1.22 pg/ml), ICAM-1 (-45%), e-selectin (-5.57 ng/ml) CRVE (–7.00 μm) and % FMD (-9.8%). Sub-study 2: Each IQR increment increase in NO2 (7.0 μg/m³) was associated with VEGF (-18.9%), CRVE (-2.93 μm) and baseline brachial artery diameter (-0.29 μm). Benzene (IQR: 3.3 μg/m³) was associated with p-selectin (-5.8 pg/ml), toluene (IQR: 30.0 μg/m³) was associated with PA1-1 (7.2 ng/ml). Ethyl-benzene (IQR: 3.8 μg/m³) was associated with VCAM-1 (-4.9%) and PA1-1 (9.1 ng/ml). m+p-Xylene and o-Xylene (IQR 3.8 μg/m³ respectively) were associated with VCAM-1 (-1.47% and -4.5%) and PA1 (3.08 ng/ml and 11.7 ng/ml). 3+4MHA (1380 ng/ml) was associated with %FMD (-0.40%). Discussion and Conclusion: The study showed that endothelial function is a marker of effect of HIV, ART and air pollutants (NO2 and BTEX) in the current study population, and that HIV and air pollution contribute to an increased cardiovascular risk profile while ART exhibited varying effects. This study underscores the relevance of these emerging cardiovascular risk factors in South Africa and the greater sub-Saharan Africa region. This study strongly supports the need for further investigation, also in study populations beyond the Western Cape.
- ItemInvestigating the cardiovascular effects of antiretroviral drugs in a lean and high fat/sucrose diet rat model of obesity : an in vivo and ex vivo approach(Stellenbosch : Stellenbosch University, 2016-03) Everson, Frans Pieter; Genis, Amanda; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Medical Physiology.ENGLISH ABSTRACT: Introduction: An interaction exists between cardiovascular risk factors (e.g. obesity) and antiretroviral treatment (ART) in the pathogenesis of cardiovascular disease. While ART reverses HIV- related weight loss, studies investigating ART effects in the context of obesity are lacking. Objective: To investigate the effects of Odumine® (first-line fixed ART-drug combination) on several cardio-metabolic parameters in a high fat/sucrose diet (HFD) rat model of obesity. Methods: Groups: Lean, untreated (C/-ART); HFD, untreated (HFD/-ART); Lean, treated (C/+ART); HFD, treated (HF/+ART). Sample size: n = 28 - 34 / group; male Wistar rats. The HFD feeding programme followed for 16 weeks and ART treatment programme for the last 6 weeks of HFD feeding programme. The Endpoints measured included: Food and water consumption for the first 31 days during the drug treatment programme; Biometric measurements: Total body mass (TBM), intra-peritoneal (IP) fat mass, heart mass and liver mass; Blood and serum: Glucose, insulin, total cholesterol (TC), triglycerides (TGs); Thiobarbituric acid reactive substance (TBARS) and conjugated dienes (CD); Isolated heart perfusion: Functional recovery (Global ischaemia-reperfusion) and infarct sizes (Regional ishcaemia-reperfusion); Western blot (Pre- and post-ischaemia-reperfusion): Nitric oxide synthase (NOS) signalling (eNOS, PKB/Akt and AMPK), indicators of reactive oxygen species (ROS) (Nitrotyrosine and p22 phox) and an indicator of pro-inflammatory NF-κB signalling (IκBα) in heart tissue. Results: The HFD was validated by increases in TBM, IP fat mass and heart mass. The HFD was further validated by increased TG and TBARS levels (lipid peroxidation). Pre-ischaemia-reperfusion, the HFD was associated with reduced oxidative stress (nitrotyrosine and p22 phox) vs. C/-ART. Reduced oxidative stress was associated with increased activation of the pro-inflammatory NF-κB pathway. The HFD upregulated eNOS post-ischaemia- reperfusion, downregulated PKB/Akt and increased NF-κB activation. Lastly, the HFD was associated with reduced functional recovery vs. C/-ART and HF/+ART, and increased infarct size vs. C/-ART and HF/+ART. ART treatment did not affect the food and water consumption, was associated with reduced insulin levels vs. C/-ART and HF/+ART, increased TC levels vs. C/-ART and elevated levels of oxidative stress (increased TBARS) vs. C/-ART. Pre-ischaemia- reperfusion, ART improved oxidative stress in heart tissue (reduced p22 phox) vs. C/-ART and reduced inflammation (downregulated IκBα). Post-ichaemia-reperfusion, ART upregulated eNOS in the heart tissue, downregulated PKB/Akt and increased oxidative stress (nitrotyrosine) vs. C/-ART. ART per se did not affect functional recovery or infarct size. The HFD combined with ART increased liver mass vs. HF/-ART. Pre-ischaemia- reperfusion, HFD/+ART improved oxidative stress (decreased nitrotyrosine and p22 phox) vs. HF/-ART, but decreased NF-κB activation vs. HF/-ART. Post-ischaemia-reperfusion, ART combined with HFD upregulated eNOS, downregulated PKB/Akt and increased oxidative stress (p22 phox) vs. HF/-ART and C/+ART. Post-ischaemia-reperfusion, ART with HFD seemed to improved functional recovery vs. HF/-ART and ameliorated the increased infarct size vs. HF/-ART. Discussion and Conclusion: Our study demonstrates the detrimental effect of HFD/obesity on cardiovascular health. Interestingly, when combined with ART, cardiovascular function seem to be improved vs. HFD/-ART. ART alone, affected cardiovascular health to a lesser extent in our study vs. HF/-ART and HF/+ART, and did not affect functional recovery and infarct size vs. C/-ART at all.