权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Altered mitochondrial function and HIV-associatedcardiometabolic disease in populations from South Africa and Kenya (MITO-SAKen)

南非和肯尼亚人群线粒体功能改变和 HIV 相关心脏代谢疾病 (MITO-SAKen)

基本信息

批准号：
10534828
负责人：
Hans Strijdom
金额：
$ 14.46万
依托单位：
STELLENBOSCH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-12 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10534828
关键词：
AIDS/HIV problem Address Adenosine Triphosphate Africa South of the Sahara African Aging Air Pollution Apoptosis Biogenesis Cardiometabolic Disease Cardiovascular system Cell Aging Cell Extracts Chronic Clinical Research Coenzyme Q10 Communicable Diseases Complement Cross-Sectional Studies Data Development Diabetes Mellitus Disease Eastern Africa Elderly Electron Transport Endocrine Epidemiology Exposure to Fluorometry Fumarates Functional disorder Funding Gene Expression Gene Expression Profiling Genes Genetic Transcription Grant HIV HIV Infections HIV antiretroviral Health Resources High Density Lipoprotein Cholesterol High Prevalence Hyperglycemia Hypertension Hypertriglyceridemia Immunologics Impairment In Vitro Inflammation Inflammatory Institution Integrase Inhibitors Kenya Kidney Diseases Knowledge Lead Link Liver diseases Measures Membrane Potentials Metabolic Metabolic syndrome Mission Mitochondria Mitochondrial DNA NIH Office of AIDS Research National Institute of Diabetes and Digestive and Kidney Diseases Nucleosides Obesity Oxidative Phosphorylation Oxidative Stress Participant Pathogenesis Pathology Peripheral Blood Mononuclear Cell Persons Pharmaceutical Preparations Polymerase Chain Reaction Population Process Production Public Health RNA Reactive Oxygen Species Regimen Research Research Priority Resolution Respiration Respiratory physiology Reverse Transcriptase Inhibitors Reverse Transcription Risk Risk Factors Sampling Smoking South Africa Southern Africa Subgroup Technology Tenofovir Testing Time Toxic effect Transmembrane Transport Tuberculosis United States National Institutes of Health Weight Gain aged antiretroviral therapy base burden of illness cardiometabolic risk cardiometabolism co-infection cohort comorbidity disorder control disorder risk epidemiologic data epidemiology study experience experimental study immune activation infection rate insight lifestyle factors low and middle-income countries mRNA Expression mitochondrial dysfunction mitochondrial membrane mortality novel pathogen recruit screening trend

项目摘要

PROJECT SUMMARY Current evidence suggests that sub-Saharan Africa is facing a double burden of disease, with HIV and cardi- ometabolic disease seemingly on a collision course. This is compounded by the growing burden of cardiometa- bolic disease attributable to HIV, which will further impact already struggling public health resources in the region. The relative lack of epidemiological and mechanistic studies on the intersection between HIV and cardiometa- bolic disease in sub-Saharan African populations therefore represents a major knowledge gap. Several factors, including mitochondrial dysfunction, are implicated in the pathogenesis of HIV-associated cardiometabolic dis- ease. Mitochondrial dysfunction has been linked to both HIV and cardiometabolic disease and previous studies have demonstrated mitochondrial involvement in several cardiometabolic-related pathologies in people living with HIV (PLWH). Whilst a common underlying mechanism of HIV-associated cardiometabolic disease remains elusive, mitochondrial dysfunction may uniquely drive the pathogenesis of cardiometabolic disease to a greater extent in people with compared to without HIV. PLWH in sub-Saharan Africa are particularly susceptible to mi- tochondrial dysfunction due to a unique convergence of intrinsic and extrinsic risk factors, including exposure to endemic pathogens and high levels of inflammation. In this study, it is hypothesized that antiretroviral therapy (ART)-experienced PLWH with cardiometabolic disease in sub-Saharan Africa will show greater mitochondrial dysfunction compared to PLWH without cardiometabolic disease and controls without HIV. The hypothesis will be tested in an exploratory, cross-sectional study comprising cohorts in South Africa and Kenya. In Specific Aim 1, mitochondrial respiratory function (measured by state-of-the-art high resolution respirometry and fluorometry technology) will be compared in participants with and without HIV, and it will be determined whether mitochon- drial dysfunction is more pronounced in PLWH with cardiometabolic disease. In Specific Aim 2, mRNA expres- sion of genes linked to mitochondrial function and dynamics will be compared in participants with and without HIV, and it will be determined whether gene expression is different in PLWH with cardiometabolic disease. Re- lated pathophysiological processes, including inflammatory, immunological and endocrine, will be measured to complement the mitochondrial function and gene expression experiments in Aims 1 and 2. This exploratory study will provide preliminary evidence that heightened mitochondrial dysfunction is present in PLWH with cardiomet- abolic disease from South Africa and Kenya. These results may benefit public health in the region, including screening of PLWH at risk of mitochondrial dysfunction, revision of 1st line ART that includes drugs with mito- chondrial toxicity, and stronger emphasis on cardiometabolic disease in PLWH. New research networks in South Africa, Kenya and the US will be forged, with a strong capacity development focus.

项目总结