Research Articles (Medical Physiology)
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- ItemCross-sectional study of the association of 5 single nucleotide polymorphisms with enalapril treatment response among South African adults with hypertension(Wolters Kluwer Health, 2021) Masilela, Charity; Pearce, Brendon; Ongole, Joven Jebio; Adeniyi, Oladele Vincent; Johnson, Rabia; Benjeddou, MongiThis study investigates the association of 5 single nucleotide polymorphisms (SNPs) in selected genes (ABO, VEGFA, BDKRB2, NOS3, and ADRB2) with blood pressure (BP) response to enalapril. The study further assessed genetic interactions that exist within these genes and their implications in enalapril treatment response among South African adults with hypertension. A total of 284 participants belonging to the Nguni tribe of South Africa on continuous treatment for hypertension were recruited. Five SNPs in enalapril pharmacogenes were selected and genotyped using MassArray. Uncontrolled hypertension was defined as BP ≥140/90 mm Hg. The association between genotypes, alleles, and BP response to treatment was determined by fitting multivariate logistic regression model analysis, and genetic interactions between SNPs were assessed by multifactor dimensionality reduction. Majority of the study participants were female (75.00%), Xhosa (78.87%), and had uncontrolled hypertension (69.37%). All 5 SNPs were exclusively detected among Swati and Zulu participants. In the multivariate (adjusted) logistic model analysis, ADRB2 rs1042714 GC (adjusted odds ratio [AOR] = 2.31; 95% confidence interval [CI] 1.02–5.23; P = .044) and BDKRB2 rs1799722 CT (AOR = 2.74; 95% CI 1.19–6.28; P = .017) were independently associated with controlled hypertension in response to enalapril. While the C allele of VEGFA rs699947 (AOR = 0.37; 95% CI 0.15–0.94; P = .037) was significantly associated with uncontrolled hypertension. A significant interaction between rs699947, rs495828, and rs2070744 (cross-validation consistency = 10/10; P = .0005) in response to enalapril was observed. We confirmed the association of rs1042714 (ADRB2) and rs1799722 (BDKRB2) with controlled hypertension and established an interaction between rs699947 (VEGFA), rs495828 (ABO), and rs2070744 (NOS3) with BP response to enalapril. Our findings have provided substantial evidence for the use of SNPs as predictors for enalapril response among South Africans adults with hypertension.
- ItemEditorial: Role of Mitochondrial Quality Control in Myocardial and Microvascular Physiology and Pathophysiology(Frontiers Media S.A, 2021-09) Lochner, Amanda; Wang, Hsueh-Hsiao; Reiter, Russel J.; Guo, Rui; Zhou, HaoMitochondrial quality control (MQC) involves a series of adaptive responses of mitochondrial morphological alterations and functional modifications, such as mitochondrial fusion, mitochondrial fission, mitophagy, mitochondrial biogenesis, mitochondrial bioenergetics, and mitochondria-mediated death pathways (Akbari et al., 2019; Del Campo, 2019; Shanmughapriya et al., 2020; Wang et al., 2020c). Mitochondrial damage or impaired MQC has been reported to play an important role in regulating the physiology and/or pathology of myocardium and vessels (Heusch, 2019; Hughes et al., 2020; Wang and Zhou, 2020; Wang et al., 2020b). The objective role of the Research Topic “Role of Mitochondrial Quality Control in Myocardial and Microvascular Physiology and Pathophysiology” (https://www.frontiersin.org/research-topics/13532/role-of-mitochondrial-quality-control-in-myocardial-and-microvascular-physiology-and-pathophysiology#research-topic-overview) was to gather original research articles and/or reviews to highlight the recent findings regarding the impact of MQC on various cardiovascular disorders. The article “Physical exercise: a novel tool to protect mitochondrial health” by Sorriento et al. reviews the effects of physical activity on cardiac mitochondrial function underlying the ability to modulate specific steps in mitochondrial quality control in both physiological and pathophysiological conditions. Topics were discussed ranged from the effects of exercise on mitochondrial phenotypes, biogenesis, turnover, morphology and respiration to cardiac pathophysiological conditions such as, aging, ischemia/reperfusion injury (I/R), diabetic cardiomyopathy, and anthracyclines dependent heart failure. From these studies, physical exercise emerges as a non-pharmacological tool (“mitochondrial medicine for muscle”) to improve cardiovascular fitness in healthy people as well as to attenuate mitochondrial dysfunction in patients with pathophysiological conditions, particularly cardiac I/R damage.
- ItemHypertension in African populations: review and computational insights(MDPI, 2021-04) Mabhida, Sihle E.; Mashatola, Lebohang; Kaur, Mandeep; Sharma, Jyoti R.; Apalata, Teke; Muhamed, Babu; Benjeddou, Mongi; Johnson, RabiaHypertension (HTN) is a persistent public health problem affecting approximately 1.3 billion individuals globally. Treatment-resistant hypertension (TRH) is defined as high blood pressure (BP) in a hypertensive patient that remains above goal despite use of ≥3 antihypertensive agents of different classes including a diuretic. Despite a plethora of treatment options available, only 31.0% of individuals have their HTN controlled. Interindividual genetic variability to drug response might explain this disappointing outcome because of genetic polymorphisms. Additionally, the poor knowledge of pathophysiological mechanisms underlying hypertensive disease and the long-term interaction of antihypertensive drugs with blood pressure control mechanisms further aggravates the problem. Furthermore, in Africa, there is a paucity of pharmacogenomic data on the treatment of resistant hypertension. Therefore, identification of genetic signals having the potential to predict the response of a drug for a given individual in an African population has been the subject of intensive investigation. In this review, we aim to systematically extract and discuss African evidence on the genetic variation, and pharmacogenomics towards the treatment of HTN. Furthermore, in silico methods are utilized to elucidate biological processes that will aid in identifying novel drug targets for the treatment of resistant hypertension in an African population. To provide an expanded view of genetic variants associated with the development of HTN, this study was performed using publicly available databases such as PubMed, Scopus, Web of Science, African Journal Online, PharmGKB searching for relevant papers between 1984 and 2020. A total of 2784 articles were reviewed, and only 42 studies were included following the inclusion criteria. Twenty studies reported associations with HTN and genes such as AGT (rs699), ACE (rs1799752), NOS3 (rs1799983), MTHFR (rs1801133), AGTR1 (rs5186), while twenty-two studies did not show any association within the African population. Thereafter, an in silico predictive approach was utilized to identify several genes including CLCNKB, CYPB11B2, SH2B2, STK9, and TBX5 which may act as potential drug targets because they are involved in pathways known to influence blood pressure. Next, co-expressed genes were identified as they are controlled by the same transcriptional regulatory program and may potentially be more effective as multiple drug targets in the treatment regimens for HTN. Genes belonging to the co-expressed gene cluster, ACE, AGT, AGTR1, AGTR2, and NOS3 as well as CSK and ADRG1 showed enrichment of G-protein-coupled receptor activity, the classical targets of drug discovery, which mediate cellular signaling processes. The latter is of importance, as the targeting of co-regulatory gene clusters will allow for the development of more effective HTN drug targets that could decrease the prevalence of both controlled and TRH.
- ItemHIV and antiretroviral therapy are independently associated with cardiometabolic variables and cardiac electrical activity in adults from the Western Cape Region of South Africa(MDPI, 2021-09) Williams, Cassidy; Kamau, Festus M.; Everson, Frans; Kgokane, Boipelo; De Boever, Patrick; Goswami, Nandu; Webster, Ingrid; Strijdom, HansCardiovascular-related complications are on the rise in people with HIV/AIDS (PWH); however, the relationship among HIV and antiretroviral therapy (ART)-related parameters, cardiovascular risk, and cardiac electrical activity in PWH remain poorly studied, especially in sub-Saharan African populations. We investigated whether HIV and ART are associated with cardiometabolic and cardiac electrical activity in PWH from Worcester in theWestern Cape Province, South Africa. This was a cross-sectional study with HIV-negative (HIV�����, n = 24) and HIV-positive on ART (HIV+/ART+, n = 63) participants. We obtained demographic, lifestyle, and medical history data and performed anthropometric, clinical assessments, and blood/urine biochemistry. We performed multiple stepwise linear regression analyses to determine independent associations among HIV, ART, cardiometabolic, and electrocardiographic (ECG) variables. HIV+/ART+ independently associated with a lower body mass index (p = 0.004), elevated gamma-glutamyl transferase levels ( : 0.333 (0.130–0.573); p = 0.002), and elevated alanine aminotransferase levels ( : 0.427 (0.224–0.629); p < 0.001) compared to HIV�����. Use of second-line ART was positively associated with high-sensitivity C-reactive protein (p = 0.002). Although ECG parameters did not differ between HIV����� and HIV+/ART+, viral load positively associated with p-wave duration (0.306 (0.018–0.594); p = 0.038), and longer HIV duration ( 5 years) with ST-interval (0.270 (0.003–0.537); p = 0.047) after adjusting for confounding factors. Our findings suggest that HIV and ART are associated with mixed effects on this population’s cardiometabolic profile and cardiac electrical activity, underpinning the importance of cardiovascular risk monitoring in PWH.
- ItemRelationship between Endothelial Function, Antiretroviral Treatment and Cardiovascular Risk Factors in HIV Patients of African Descent in South Africa: A Cross-Sectional Study(MDPI, 2021-01-20) Nkeh-Chungag, Benedicta N.; Goswami, Nandu; Engwa, Godwill A.; Sewani-Rusike, Constance R.; Mbombela, Vuyolwethu; Webster, Ingrid; De Boever, Patrick; Kessler, Harald H.; Stelzl, Evelyn; Strijdom, HansLimited information on the effect of antiretroviral treatment (ART) on vascular function in South Africans of African descent living with human immunodeficiency virus (HIV) is available. The relationship between ART, vascular function and cardiovascular risk factors in South Africans of African ancestry with HIV was therefore studied. This cross-sectional study recruited 146 HIVpositive individuals on ART (HIV+ART+), 163 HIV-positive individuals not on ART (HIV+ART�����) and 171 individuals without HIV (HIV�����) in Mthatha, Eastern Cape Province of South Africa. Flowmediated dilation (FMD) test was performed to assess endothelial function. Anthropometry and blood pressure parameters were measured. Lipid profile, glycaemic indices, serum creatinine as well as CD4 count and viral load were assayed in blood. Urinary albumin to creatinine ratio (ACR) was determined as a marker of cardiovascular risk. Obesity and albuminuria were positively associated with HIV, and HIV+ART+ participants had significantly higher HDL cholesterol. Dyslipidaemia markers were significantly higher in hypertensive HIV+ART+ participants compared with the controls (HIV+ART����� and HIV����� participants). FMD was not different between HIV+ART+ participants and the controls. Moreover, HIV+ART+ participants with higher FMD showed lower total cholesterol and LDL cholesterol comparable to that of HIV����� and HIV+ART����� participants. A positive relationship between FMD and CD4 count was observed in HIV+ART+ participants. In conclusion, antiretroviral treatment was associated with cardiovascular risk factors, particularly dyslipidaemia, in hypertensive South Africans of African ancestry with HIV. Although, ART was not associated with endothelial dysfunction, flow-mediated dilatation was positively associated with CD4 count in HIV-positive participants on ART.