Department of Medicine Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Cardiovascular Pulmonary Research Labs and Pediatric Critical Care Medicine, University of Colorado Denver, Pediatric Critical Care Medicine, Aurora, CO 80045, USA.
Int J Mol Sci. 2020 May 7;21(9):3305. doi: 10.3390/ijms21093305.
The HIV-infected population is at a dramatically increased risk of developing pulmonary arterial hypertension (PAH), a devastating and fatal cardiopulmonary disease that is rare amongst the general population. It is increasingly apparent that PAH is a disease with complex and heterogeneous cellular and molecular pathologies, and options for therapeutic intervention are limited, resulting in poor clinical outcomes for affected patients. A number of soluble HIV factors have been implicated in driving the cellular pathologies associated with PAH through perturbations of various signaling and regulatory networks of uninfected bystander cells in the pulmonary vasculature. While these mechanisms are likely numerous and multifaceted, the overlapping features of PAH cellular pathologies and the effects of viral factors on related cell types provide clues as to the potential mechanisms driving HIV-PAH etiology and progression. In this review, we discuss the link between the DNA damage response (DDR) signaling network, chronic HIV infection, and potential contributions to the development of pulmonary arterial hypertension in chronically HIV-infected individuals.
HIV 感染者发生肺动脉高压（PAH）的风险显著增加，PAH 是一种严重且致命的心肺疾病，在普通人群中较为罕见。越来越多的证据表明，PAH 是一种具有复杂和异质性细胞及分子病理学的疾病，治疗干预的选择有限，导致受影响患者的临床结局较差。许多可溶性 HIV 因子通过干扰肺血管中未受感染旁观者细胞的各种信号和调节网络，参与驱动与 PAH 相关的细胞病理学。虽然这些机制可能很多且多方面，但 PAH 细胞病理学的重叠特征以及病毒因子对相关细胞类型的影响，为驱动 HIV-PAH 病因和进展的潜在机制提供了线索。在这篇综述中，我们讨论了 DNA 损伤反应（DDR）信号网络、慢性 HIV 感染以及对慢性 HIV 感染者发生肺动脉高压的潜在贡献之间的联系。
