School of Physiology (ETDs)

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Browsing School of Physiology (ETDs) by Keyword "Cardiovascular disease"

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    Determinant of metabolic syndrome and its cardiovascular complications among people of African ancestry
    (2024) Eluwole, Omotayo Alaba
    Cardiovascular disease is now a leading cause of death globally. However, metabolic syndrome is an extremely critical healthcare issue worldwide due to progressive increase in obesity and its related factors. Obesity is strongly associated with insulin resistance and other components of metabolic syndrome. There is discrepancy in the use of parameters for the diagnostic criteria of metabolic syndrome due to genetic and environmental variability in different ethnicity. Body mass index and waist circumference (WC) are commonly used in the assessment of central obesity and abdominal obesity respectively. Fahed et al observed that waist circumference was employed because measurement was easy, however, waist circumference alone is inconclusive of abdominal adiposity and must be interpreted with body mass index. The two measurements (WC and BMI) have been documented to be strongly related to insulin resistance. (Fahed et al., 2022). However, there is controversial assessment of metabolic syndrome using either waist circumference (WC) or body mass index (BMI) or waist hip ratio (WHR) or combination of two measurements (Kassi et al., 2011; Fahed et al., 2022). Our study assessed the prevalence of metabolic syndrome among apparently healthy 1516 participants from African ancestry using seven established diagnostic criteria (NCEP-ATPIII- National Cholesterol Education Program Adult Treatment Panel III, WHO- World Health Organization, IDF-International Diabetes Federation, AHA/NHLBIAmerican Heart Association/National Heart, Lung and Blood Institute, EGIR - European Group for the study of Insulin Resistance, AACE- American Association of Clinical Endocrinology). The result revealed highest prevalence of metabolic syndrome when modified NCEP-ATPIII [National Cholesterol Education Program Adult Treatment Panel III (ATP III)] was considered. The predictive assessment of blood pressure and arterial stiffness may be useful in achieving early detection and prevention of target organ damage. This study further compared clinic blood pressure, ambulatory blood pressure and central pressure using conventional blood pressure monitor, Spacelabs 90207 (Spacelabs Inc., Redmond, Washington, USA) and applanation tonometry Sphygmocor device respectively. The findings revealed that central blood pressure and ambulatory blood pressure are more predictive of cardiovascular events among people of African ancestry. Our findings are pointers to cardiovascular risk in the study population. Additionally, this study provides new insights to the role of obesity in the perturbation of left ventricular geometry of people of African ancestry with metabolic syndrome; using quantitative and comprehensive evaluation of biochemical and echocardiographic profile. Aldosterone produced locally in adipose tissue, heart, kidney and vasculature increase the expression of cytokines and other fibrotic factors. Thus, role of the local renin angiotensin aldosterone system (RAAS) in the pathophysiology of atherosclerosis and cardio-renal fibrosis was evaluated in animal study. With high prevalence of metabolic syndrome and obesity in Africans, elevated aldosterone from diet may likely predispose African community to diastolic dysfunction; this may be a pointer to increased incidence of heart failure in groups of African ancestry. Hence, this study lends insights into the potential role of TRPM7; a novel non selective cation channel and chanzyme in aldosterone-induced cardiovascular fibrosis. This study concluded that modified NCEP-ATPIII has suitable components for the diagnosis of MS in people of African ancestry. Metabolic syndrome in people of African ancestry is strongly associated with factors such as sex, smoking and alcohol. Consequently, MS and other risk factors such as obesity, aldosterone and insulin resistance may lead to left diastolic dysfunction among individuals with MS. Experimentally, aldosterone-salt induced cardio-renal fibrosis, aggravated by TRPM7 might be the underlying pathogenesis of MS and its cardiovascular complications in Africans; thus suggests TRMP7 inhibitors has potential anti-fibrotic agents.
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    MicroRNA expression and arterial function in type II diabetes mellitus
    (University of the Witwatersrand, Johannesburg, 2024) Goldfein, Batsheva; Millen, Aletta
    Background. Type II diabetes mellitus (T2DM) is a major health concern which significantly contributes to the global cardiovascular disease (CVD) burden. Arterial dysfunction is considered a subclinical marker of CVD and is associated with an increased risk of cardiovascular events. However, treatment outcomes for T2DM patients remain suboptimal, mainly due to a poor understanding and the lack of an early marker for the identification of subclinical CVD. Recently, microRNAs (miRNA), small, non-coding RNA molecules that regulate major signalling pathways through post-transcriptional modification, have been identified as possible epigenetic regulators in the development of many diseases. MiR-146a-5p, in particular, has received considerable attention as a biomarker associated with several disease states including inflammation, T2DM and CVD. However, studies surrounding the role of miR- 146a-5p in arterial function and subclinical CVD risk in diabetic populations have yielded contradictory results. Therefore, the aim of this study was to determine the role of miR-146a-5p expression in the development of arterial dysfunction in patients with T2DM. Methods. This case control study (n=118) included participants with a previous diagnosis of insulin resistance or T2DM (n=67), and a non-DM control group (n=51). Demographic characteristics and CVD risk factors were assessed using standard approaches. Arterial function was measured using applanation tonometry and SphygmoCor software. From the recorded radial and aortic waveforms, central systolic (cSBP) and pulse pressure (cPP), augmentation pressure (AP) and the forward (FWP) and reflected wave pressure (RWP) were derived using a generalised transfer function. The carotid-femoral pulse wave velocity (PWV) was measured as a marker of arterial stiffness. Using a fasting blood sample, serum concentrations of tumour necrosis factor α (TNFα) and matrix metalloproteinase 1 (MMP1) were quantified by ELISA. Real time quantitative PCR was used to determine the relative expression of miR-146a-5p using the comparative CT method relative to an endogenous control miRNA, miR-16-5p. Differences in anthropometric variables, miRNA expression and arterial function between the two groups were determined using unpaired t-tests or Mann Whitney U tests, as appropriate. Associations between miR-146a-5p expression and arterial function were determined using Pearson’s correlations. Participants were further stratified according to CVD risk using the Framingham risk score (FRS), and the associations with miRNA expression analysed using multivariate linear regression. Results. Participants with DM had significantly higher body mass index (p=0.002), triglyceride levels (p=0.004), and systolic blood pressure (p<0.001) than the control participants. Diabetic participants also had increased CVD risk compared to the control group, as assessed using FRS (P<0.001). Participants with DM also had significantly higher cSBP (p=0.003), mean arterial pressure (p<0.001), peripheral PP (p=0.04), FWP (p=0.045) and PWV (p=0.04). The relative expression of miR-146a-5p was significantly increased in the DM group compared to the control group (p=0.02). Across the study cohort, miR-146a-5p expression was significantly associated with waist-to- hip ratio (partial r=0.29, p = 0.002), triglyceride concentrations (partial r=0.2, p = 0.04), the atherogenic index (partial r=0.20, p=0.04) and TNFα concentrations (partial r=0.23, p=0.02), in age, sex and race adjusted analysis. In multivariate adjusted analysis, miR- 146a-5p expression was not associated with any of the arterial function variables (all p>0.05). However, when stratifying participants based on CVD risk, in those with a high risk for CVD (FRS≥20), miR-146a-5p was inversely associated with peripheral PP (Std β=-0.76, p=0.03, cPP (Std β=-0.76, p=0.01), cSBP (Std β=-0.38, p=0.02), FWP (Std β=-0.68, p=0.04) and RWP (Std β=-0.66, p=0.04). When MMP1 was included as a confounder, these associations were no longer significant. Conclusion. MiR-146a-5p expression was significantly higher in participants with T2DM compared to control participants and was significantly associated with traditional CVD risk factors and inflammation. MiR-146a-5p expression was not association with arterial function measures in the total population. Interestingly, in patients at a high risk for CVD, decreased expression of miR-146a-5p was associated with increased pressure pulsatility and wave reflection. These associations were lost when MMP1, a marker of arterial remodelling, was included as a confounding factor. These results suggest that miR-146a-5p may have a regulatory role in the development of arterial dysfunction through arterial remodelling in persons at high risk for CVD.