HIV INFECTION/COCAINE EFFECT ON CARDIOVASCULAR PATHOLOGY

HIV 感染/可卡因对心血管病理的影响

• 批准号: 6638547
• 负责人: Aftab A. Ansari
• 金额: $ 30.4万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6638547
• 关键词: HIV infections; cardiovascular disorder; catecholamines; cell cell interaction; cell proliferation; cocaine; cytomegalovirus; disease /disorder etiology; drug abuse; drug interactions; gene expression; human immunodeficiency virus 1; latent virus infection; metalloendopeptidases; pathologic process; simian immunodeficiency virus; tissue /cell culture; vascular endothelium; vascular smooth muscle

The etiology of HIV-related cardiovascular disease (CVD) specially in patients with a history of cocaine use is most likely multifactorial. This is highlighted by the finding that there is an increase in the incidence of CVD in individuals with a history of cocaine abuse who are not HIV-1 infected and a similar increase in CVD in HIV-1 infected individuals who have no history of drug use. In addition, marked vascular lesions have been documented in SIV infected juvenile rhesus macaques who have no history of drug use. Thus, the effects of cocaine and HIV-1 infection leading to CVD may operate by separate but overlapping pathways, synergistically accelerating the disease process. It is our working hypothesis that insult to the vascular endothelium is one of the factor that contributes to CVD in HIV-1 infection which is further exacerbated by the use of drugs such as cocaine. Our lab has been studying the biology of lymphoid-endothelial cell interaction in both humans and non-human primates (NHP) in a variety of settings including responses to viral infections. During this process we have acquired unique sets of reagents, tools, techniques, knowledge, experience and important preliminary data which we submit will aid in defining some of the mechanisms of pathogenesis of HIV and cocaine induced cardiac disease. Specifically, we propose to a) determine if HIV/SIV infected lymphoid cells show increased adherence to human and NHP microvascular endothelial cells (MVEC), respectively in the presence/absence of cocaine/catecholamines using both a static and dynamic culture system b) to define the effect of HIV/SIV infected lymphoid cells in the presence and absence of cocaine/catecholamine on the expression of select cell adhesion/costimulatory molecule (CAM/CSM's), cytokines and chemokines by human and NHP MVEC c) determine if the effect on CAM/CSM's, cytokines and chemokines requires a disease inducing lentivirus isolate d) determine if HIV infected lymphoid cells in the presence/absence of cocaine/catecholamine induces the breakdown of latency in latent CMV infected autologous aortic endothelial cells e) determine if co-culture of MVEC and autologous smooth muscle cells (SMC's) in the presence of cocaine/catecholamine alone, HIV/SIV infected autologous cells alone or in combination leads to SMC proliferation and remodeling and, f) determine whether interaction of HIV-1/SIV infected cells alone and/or in the presence of cocaine/catecholamine leads to the synthesis of metalloproteinases. We reason that such studies may provide unique insights on the relationship between the effects of cocaine and HIV infection in the pathogenesis of cardiovascular disease.

HIV 相关心血管疾病 (CVD) 的病因很可能是多因素的，尤其是有可卡因使用史的患者。 研究结果强调了这一点：有可卡因滥用史但未感染 HIV-1 的个体的 CVD 发病率有所增加，而在没有吸毒史的 HIV-1 感染者的 CVD 发病率也有类似的增加。 此外，在没有吸毒史的感染 SIV 的幼年恒河猴中也发现了明显的血管病变。 因此，可卡因和 HIV-1 感染导致 CVD 的作用可能通过独立但重叠的途径发挥作用，协同加速疾病进程。 我们的工作假设是，对血管内皮的损伤是导致 HIV-1 感染中 CVD 的因素之一，而使用可卡因等药物会进一步加剧这种损伤。我们的实验室一直在研究人类和非人类灵长类动物 (NHP) 在各种环境下淋巴-内皮细胞相互作用的生物学，包括对病毒感染的反应。在此过程中，我们获得了独特的试剂、工具、技术、知识、经验和重要的初步数据，我们提交的这些数据将有助于确定艾滋病毒和可卡因诱发的心脏病的一些发病机制。 具体来说，我们建议 a) 使用静态和动态培养系统分别在存在/不存在可卡因/儿茶酚胺的情况下确定 HIV/SIV 感染的淋巴细胞是否表现出对人和 NHP 微血管内皮细胞 (MVEC) 的粘附增加 b) 确定在存在和不存在可卡因/儿茶酚胺的情况下感染 HIV/SIV 的淋巴细胞对表达的影响 c) 确定对 CAM/CSM、细胞因子和趋化因子的影响是否需要诱导慢病毒分离株的疾病 d) 确定在存在/不存在可卡因/儿茶酚胺的情况下，HIV 感染的淋巴细胞是否会诱导潜伏期的破坏 CMV 感染的自体主动脉内皮细胞 e) 确定在单独的可卡因/儿茶酚胺、HIV/SIV 感染的自体细胞单独或组合存在下，MVEC 和自体平滑肌细胞 (SMC) 的共培养是否会导致 SMC 增殖和重塑，f) 确定单独的 HIV-1/SIV 感染细胞和/或在 可卡因/儿茶酚胺导致金属蛋白酶的合成。 我们认为，此类研究可能为可卡因与艾滋病毒感染在心血管疾病发病机制中的影响之间的关系提供独特的见解。

项目成果

Combined pathological effects of cocaine abuse and HIV infection on the cardiovascular system: an autopsy study of 187 cases from the Fulton County Medical Examiner's office.

可卡因滥用和 HIV 感染对心血管系统的综合病理影响：对富尔顿县法医办公室 187 例病例进行的尸检研究。

• DOI: 10.1097/paf.0b013e318165152f
• 发表时间: 2008
• 期刊: The American journal of forensic medicine and pathology
• 作者: Mosunjac,MarioI;Sundstrom,JBruce;Heninger,Michael;Ansari,AftabA;Mosunjac,MarinaB
• 通讯作者: Mosunjac,MarinaB

Norepinephrine enhances adhesion of HIV-1-infected leukocytes to cardiac microvascular endothelial cells.

去甲肾上腺素增强 HIV-1 感染的白细胞与心脏微血管内皮细胞的粘附。

• DOI: 10.1177/153537020322800613
• 发表时间: 2003
• 期刊: Experimental biology and medicine (Maywood, N.J.)
• 作者: Sundstrom,JB;Martinson,DE;Mosunjac,M;Bostik,P;McMullan,LK;Donahoe,RM;Gravanis,MB;Ansari,AA
• 通讯作者: Ansari,AA

Effects of norepinephrine, HIV type 1 infection, and leukocyte interactions with endothelial cells on the expression of matrix metalloproteinases.

去甲肾上腺素、HIV 1 型感染以及白细胞与内皮细胞相互作用对基质金属蛋白酶表达的影响。

• DOI: 10.1089/088922201753342013
• 发表时间: 2001
• 期刊: AIDS research and human retroviruses.
• 作者: Sundstrom,JB;Mosunjac,M;Martinson,DE;Bostik,P;Donahoe,RM;Gravanis,MB;Ansari,AA
• 通讯作者: Ansari,AA

Is peripartum cardiomyopathy an organ-specific autoimmune disease?

围产期心肌病是一种器官特异性自身免疫性疾病吗？

• DOI: 10.1016/s1568-9972(01)00009-x
• 发表时间: 2002
• 期刊: Autoimmunity reviews
• 影响因子: 13.6
• 作者: Sundstrom,JBruce;Fett,JamesD;Carraway,RobertD;Ansari,AftabA
• 通讯作者: Ansari,AftabA