Palakeel Jaimee J, Ali Mazin, Chaduvula Phani, Chhabra Sanika, Lamsal Lamichhane Smriti, Ramesh Vaiishnavi, Opara Collins O, Khan Farhana Yaqoob, Kabiraj Gargi, Kauser Humaira, Mostafa Jihan A
Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Cureus. 2022 Jul 28;14(7):e27390. doi: 10.7759/cureus.27390. eCollection 2022 Jul.
Although overall survival rates of patients infected with human immunodeficiency virus (HIV) have been significantly improved by antiretroviral therapy (ART), chronic comorbidities associated with HIV result in a worsening quality of life. Pulmonary arterial hypertension (PAH) is the most prevalent comorbidity associated with HIV infection. Despite low viremia and a non-replicative state maintained by ART, few people develop PAH. Previous data from animal models and human pulmonary microvascular endothelial cells (HPMVECs) suggests a constellation of events occurring during the propagation of HIV-associated PAH (HIV-PAH). However, these studies have not successfully isolated HIV virions, HIV-DNA, protein 24 antigen (p24), or HIV-RNA from the pulmonary endothelial cells (ECs). It provides an insight into an ongoing inflammatory process that could be attributed to viral proteins. Several studies have demonstrated the role of viral proteins on vascular remodeling. A composite of chronic inflammatory changes mediated by cytokines and growth factors along with several inciting risk factors such as Hepatitis C virus (HCV) co-infection, genetic factors, male predominance, illegal drug usage, and duration of HIV infection have led to molecular changes that result in an initial phase of apoptosis followed by the formation of apoptotic resistant hyperproliferative ECs with altered phenotype. This study aims to identify the risk factors and mechanisms behind HIV-PAH pathobiology at the host-pathogen interface at the intracellular level.
尽管抗逆转录病毒疗法（ART）显著提高了人类免疫缺陷病毒（HIV）感染者的总体生存率，但与HIV相关的慢性合并症导致生活质量下降。肺动脉高压（PAH）是与HIV感染相关的最常见合并症。尽管通过ART维持了低病毒血症和非复制状态，但很少有人会发展为PAH。先前来自动物模型和人肺微血管内皮细胞（HPMVECs）的数据表明，在HIV相关肺动脉高压（HIV-PAH）的发展过程中会发生一系列事件。然而，这些研究尚未成功地从肺内皮细胞（ECs）中分离出HIV病毒粒子、HIV-DNA、蛋白24抗原（p24）或HIV-RNA。这为一个可能归因于病毒蛋白的持续炎症过程提供了见解。几项研究已经证明了病毒蛋白在血管重塑中的作用。由细胞因子和生长因子介导的慢性炎症变化，以及一些诱发风险因素，如丙型肝炎病毒（HCV）合并感染、遗传因素、男性占主导、非法药物使用和HIV感染持续时间，导致了分子变化，从而导致了凋亡的初始阶段，随后形成具有改变表型的抗凋亡增殖性ECs。本研究旨在在细胞内水平上，确定宿主-病原体界面处HIV-PAH病理生物学背后的风险因素和机制。
