Atherosclerosis and Inflammation in HIV Disease

HIV 疾病中的动脉粥样硬化和炎症

• 批准号: 8319638
• 负责人: Janet Lo
• 金额: $ 14.18万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-02 至 2013-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8319638
• 关键词: Adipose tissue; Age; Angiography; Anti-Retroviral Agents; Arterial Fatty Streak; Atherosclerosis; Attenuated; Biology; Biometry; C-reactive protein; CD14 gene; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; CD8B1 gene; Cardiac; Cardiology; Cardiovascular Diseases; Cardiovascular system; Categories; Cells; Cholesterol; Chronic; Coenzyme A; Combined Modality Therapy; Communities; Coronary; Coronary Arteriosclerosis; Cytotoxic T-Lymphocytes; Development; Diabetes Mellitus; Discipline; Disease; Drug or chemical Tissue Distribution; Dyslipidemias; Endocrinology; Environment; Event; Excess Mortality; FCGR3B gene; Fatty acid glycerol esters; Future; General Population; Glucose Metabolism Disorders; Goals; Grant; HIV; HIV Infections; Health Services Accessibility; Hyperinsulinism; Image; Immune System Diseases; Individual; Infection; Inflammation; Inflammatory; Insulin Resistance; Interferons; K-Series Research Career Programs; Lead; Link; Measures; Medicine; Mentors; Mentorship; Metabolic; Oxidoreductase; Patients; Physiological; Placebo Control; Placebos; Play; Population; Pravastatin; Prevalence; Prevention strategy; Production; Randomized; Recruitment Activity; Research; Research Personnel; Risk; Risk Factors; Role; Slice; Smoking; T cell response; T-Cell Activation; T-Lymphocyte; T-Lymphocyte Subsets; Translational Research; Virus Diseases; Visceral; X-Ray Computed Tomography; abstracting; blood glucose regulation; burden of illness; cardiovascular risk factor; career development; cohort; design; detector; fluorodeoxyglucose positron emission tomography; immune function; improved; inhibitor/antagonist; monocyte; novel; patient oriented; patient population; prevent; programs; response; skills; transcription factor; treatment strategy

DESCRIPTION (provided by applicant): Survival of HIV-infected patients worldwide has remarkably improved with the use of anti-retroviral therapy. Metabolic and cardiovascular complications associated with HIV infection and its treatment are becoming more evident as this patient population ages with chronic viral infection. Metabolic and inflammatory changes in HIV-infected patients including dyslipidemia, insulin resistance, fat redistribution with abnormal adipocytokine secretion, alterations in monocyte subsets, and T-cell activation may increase the risk of atherosclerotic disease. The aims of the proposed grant are: 1) to determine the prevalence and degree of subclinical coronary atherosclerosis using CT angiography in patients with HIV compared to agematched control subjects without HIV infection, 2) to examine risk factors for coronary atherosclerosis in HIV patients, specifically evaluating the potential roles of adipocytokines, monocyte subsets, and T cell activation in atherosclerosis development, and 3) to perform a randomized, placebo-controlled, physiologic study in HIV patients with subclinical coronary atherosclerosis comparing the effects of statin therapy vs. placebo on plaque inflammation (as determined by 18F-fluorodeoxyglucose positron emission tomography), inhibition of plaque progression (as determined by coronary CT angiography), monocyte subsets and T cell response. Characterization of the atherosclerotic disease burden as well as identification of risk factors associated with atherosclerotic disease in HIV will be instrumental to guide the future design of appropriate prevention and treatment strategies for the HIV patient population. To achieve these aims, the candidate will be mentored by internationally recognized experts from several relevant disciplines in patient-oriented and translational research, endocrinology, cardiology, inflammation biology, HIV medicine, cardiac imaging, and biostatistics. Their mentorship and the strength of the candidate's institutional support will provide a well-suited academic environment to conduct this research and to nurture the candidate's career development. This K23 career development award will help the candidate to acquire the additional research skills to achieve her goal of becoming an independent patientoriented translational investigator. (End of Abstract)

描述(由申请人提供)： 随着抗逆转录病毒疗法的使用，全球艾滋病毒感染者的存活率显著提高。随着慢性病毒感染患者年龄的增长，与艾滋病毒感染及其治疗相关的代谢和心血管并发症变得更加明显。HIV感染者的代谢和炎症改变，包括血脂异常、胰岛素抵抗、脂肪重新分布和脂肪细胞因子分泌异常、单核细胞亚群改变和T细胞激活可能增加动脉粥样硬化性疾病的风险。建议拨款的目的是：1)使用CT血管造影术确定HIV患者与未感染HIV的老年对照组相比的亚临床冠状动脉粥样硬化的患病率和程度，2)检查HIV患者冠状动脉粥样硬化的危险因素，特别是评估脂肪细胞因子、单核细胞亚群和T细胞激活在动脉粥样硬化发展中的潜在作用，以及3)对HIV亚临床冠状动脉动脉粥样硬化患者进行随机、安慰剂对照的生理学研究，比较他汀类药物和安慰剂对斑块炎症的影响(由18F-氟代脱氧葡萄糖正电子发射断层扫描确定)，抑制斑块进展(由CT血管成像确定)，单核细胞亚群和T细胞反应。确定艾滋病毒中动脉粥样硬化性疾病负担的特征以及确定与动脉粥样硬化性疾病相关的风险因素将有助于指导今后为艾滋病毒患者群体设计适当的预防和治疗战略。为了实现这些目标，候选人将接受来自几个相关学科的国际公认专家的指导，这些领域包括面向患者和转译研究、内分泌学、心脏病学、炎症生物学、艾滋病毒医学、心脏成像和生物统计学。他们的指导和候选人强大的机构支持将提供一个非常合适的学术环境来进行这项研究，并促进候选人的职业发展。这项K23职业发展奖将帮助应聘者获得额外的研究技能，以实现她成为一名独立的、面向患者的翻译调查员的目标。 (摘要结束)

项目成果

High-density lipoprotein-mediated cholesterol efflux capacity is improved by treatment with antiretroviral therapy in acute human immunodeficiency virus infection.

• DOI: 10.1093/ofid/ofu108
• 发表时间: 2014-12
• 期刊: Open forum infectious diseases
• 影响因子: 4.2
• 作者: Lo J;Rosenberg ES;Fitzgerald ML;Bazner SB;Ihenachor EJ;Hawxhurst V;Borkowska AH;Wei J;Zimmerman CO;Burdo TH;Williams KC;Freeman MW;Grinspoon SK
• 通讯作者: Grinspoon SK

Increased arterial inflammation relates to high-risk coronary plaque morphology in HIV-infected patients.

• DOI: 10.1097/qai.0000000000000138
• 发表时间: 2014-06-01
• 期刊: Journal of acquired immune deficiency syndromes (1999)
• 作者: Tawakol A;Lo J;Zanni MV;Marmarelis E;Ihenachor EJ;MacNabb M;Wai B;Hoffmann U;Abbara S;Grinspoon S
• 通讯作者: Grinspoon S