Obare Laventa M, Bailin Samuel S, Zhang Xiuqi, Nthenge Kisyua, Priest Stephen, Liu Qi, Stolze Lindsey K, Sheng Quanhu, Gangula Rama, Behrens Madelaine, Jenkins Brenita, Prasad Praveena, Neikirk Kit, Prakash Prem, Hogan Meghan, Zhang Liang, Beasley Heather K, Shao Jianqiang, Miller-Fleming Tyne W, Actkins Kyera V, Phillips Mark A, Hubert David, Malone Jordan, Labeeb Cassia, Gelbard Alexander, Chaillon Antoine, Mashayekhi Mona, Gabriel Curtis L, Temu Tecla, Olson Lana, Jones Angela, Beeri Karen, Baker Paxton, Kawai Kenji, Ghosh Saikat Kumar B, Guo Laing, Virmani Renu, Finn Aloke, Shah Palak, Yang Tzushan Sharon, Bick Alexander G, Kirabo Annet, Su Yan R, Phillips Elizabeth J, Mallal Simon, Dash Chandravanu, Koethe John R, Gianella Sara, McReynolds Melanie R, Absi Tarek, Hinton Antentor, Wanjalla Celestine N
Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
Res Sq. 2024 Oct 18:rs.3.rs-5125826. doi: 10.21203/rs.3.rs-5125826/v1.
Chronic inflammation contributes to the prevalence of cardiovascular disease in people living with HIV (PLWH). The immune mechanisms driving atherosclerosis progression in PLWH remain unclear. This study conducted comprehensive assessments of medium-sized coronary arteries and aorta from deceased PLWH and controls without HIV using DNA/RNA assays, spatial transcriptomics, and high-resolution mass spectrometry. Findings revealed more significant inflammation correlated with higher HIV copy numbers in late atheroma of PLWH. Enhanced and decreased expression in CD163 macrophages were co-localized in coronaries of PLWH, suggesting a reduction in plasma lipoprotein clearance compared to controls. Spatial analyses identified potential therapeutic targets by revealing inflammatory changes in medium-sized arteries and the aorta. We examined the relationship between atherosclerotic phenotypes and inflammatory gene expression in Vanderbilts Biobank to study these findings in a larger clinical cohort. This established a significant association between and gene expressions with atherosclerosis, partly influenced by HIV.
慢性炎症导致了艾滋病毒感染者（PLWH）心血管疾病的高发。驱动PLWH动脉粥样硬化进展的免疫机制仍不清楚。本研究使用DNA/RNA检测、空间转录组学和高分辨率质谱对已故PLWH和无HIV对照者的中型冠状动脉和主动脉进行了全面评估。研究结果显示，在PLWH晚期动脉粥样硬化中，更显著的炎症与更高的HIV拷贝数相关。CD163巨噬细胞中增强和降低的表达在PLWH的冠状动脉中共定位，表明与对照组相比，血浆脂蛋白清除率降低。空间分析通过揭示中型动脉和主动脉中的炎症变化确定了潜在的治疗靶点。我们在范德比尔特生物库中研究了动脉粥样硬化表型与炎症基因表达之间的关系，以在更大的临床队列中研究这些发现。这确定了与动脉粥样硬化相关的基因表达之间存在显著关联，部分受HIV影响。
