Anand Appakkudal R, Rachel Gladys, Parthasarathy Durgadevi
L&T Microbiology Research Centre, Vision Research Foundation, Sankara Nethralaya, Chennai, India.
Department of HIV/AIDS, National Institute for Research in Tuberculosis, Chennai, India.
Front Cardiovasc Med. 2018 Dec 19;5:185. doi: 10.3389/fcvm.2018.00185. eCollection 2018.
With the success of antiretroviral therapy (ART), a dramatic decrease in viral burden and opportunistic infections and an increase in life expectancy has been observed in human immunodeficiency virus (HIV) infected individuals. However, it is now clear that HIV- infected individuals have enhanced susceptibility to non-AIDS (Acquired immunodeficiency syndrome)-related complications such as cardiovascular disease (CVD). CVDs such as atherosclerosis have become a significant cause of morbidity and mortality in individuals with HIV infection. Though studies indicate that ART itself may increase the risk to develop CVD, recent studies suggest a more important role for HIV infection in contributing to CVD independently of the traditional risk factors. Endothelial dysfunction triggered by HIV infection has been identified as a critical link between infection, inflammation/immune activation, and atherosclerosis. Considering the inability of HIV to actively replicate in endothelial cells, endothelial dysfunction depends on both HIV-encoded proteins as well as inflammatory mediators released in the microenvironment by HIV-infected cells. Indeed, the HIV proteins, gp120 (envelope glycoprotein) and Tat (transactivator of transcription), are actively secreted into the endothelial cell micro-environment during HIV infection, while Nef can be actively transferred onto endothelial cells during HIV infection. These proteins can have significant direct effects on the endothelium. These include a range of responses that contribute to endothelial dysfunction, including enhanced adhesiveness, permeability, cell proliferation, apoptosis, oxidative stress as well as activation of cytokine secretion. This review summarizes the current understanding of the interactions of HIV, specifically its proteins with endothelial cells and its implications in cardiovascular disease. We analyze recent and studies examining endothelial dysfunction in response to HIV proteins. Furthermore, we discuss the multiple mechanisms by which these viral proteins damage the vascular endothelium in HIV patients. A better understanding of the molecular mechanisms of HIV protein associated endothelial dysfunction leading to cardiovascular disease is likely to be pivotal in devising new strategies to treat and prevent cardiovascular disease in HIV-infected patients.
随着抗逆转录病毒疗法（ART）的成功，在人类免疫缺陷病毒（HIV）感染个体中已观察到病毒载量和机会性感染显著下降，预期寿命增加。然而，现在很清楚的是，HIV感染个体对非艾滋病（获得性免疫缺陷综合征）相关并发症（如心血管疾病（CVD））的易感性增强。诸如动脉粥样硬化等心血管疾病已成为HIV感染个体发病和死亡的重要原因。尽管研究表明ART本身可能会增加患心血管疾病的风险，但最近的研究表明，HIV感染在导致心血管疾病方面发挥着比传统风险因素更重要的独立作用。由HIV感染引发的内皮功能障碍已被确定为感染、炎症/免疫激活与动脉粥样硬化之间的关键联系。考虑到HIV无法在内皮细胞中主动复制，内皮功能障碍既取决于HIV编码的蛋白质，也取决于HIV感染细胞在微环境中释放的炎症介质。事实上，在HIV感染期间，HIV蛋白gp120（包膜糖蛋白）和Tat（转录反式激活因子）会被主动分泌到内皮细胞微环境中，而Nef在HIV感染期间可被主动转移到内皮细胞上。这些蛋白质可对内皮产生显著的直接影响。这些影响包括一系列导致内皮功能障碍的反应，包括增强黏附性、通透性、细胞增殖、凋亡、氧化应激以及细胞因子分泌的激活。本综述总结了目前对HIV，特别是其蛋白质与内皮细胞相互作用及其在心血管疾病中的意义的理解。我们分析了最近研究HIV蛋白引发的内皮功能障碍的研究。此外，我们讨论了这些病毒蛋白损害HIV患者血管内皮的多种机制。更好地理解HIV蛋白相关内皮功能障碍导致心血管疾病的分子机制可能对制定治疗和预防HIV感染患者心血管疾病的新策略至关重要。
