Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, QC H3C 3J7, Canada.
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC H2X 0A9, Canada.
Viruses. 2023 Mar 8;15(3):700. doi: 10.3390/v15030700.
Chronic inflammation is associated with higher risk of cardiovascular disease (CVD) in people living with HIV (PLWH). We have previously shown that interleukin-32 (IL-32), a multi-isoform proinflammatory cytokine, is chronically upregulated in PLWH and is linked with CVD. However, the mechanistic roles of the different IL-32 isoforms in CVD are yet to be identified. In this study, we aimed to investigate the potential impact of IL-32 isoforms on coronary artery endothelial cells (CAEC), whose dysfunction represents a major factor for atherosclerosis. Our results demonstrated that the predominantly expressed IL-32 isoforms (IL-32β and IL-32γ) have a selective impact on the production of the proinflammatory cytokine IL-6 by CAEC. Furthermore, these two isoforms induced endothelial cell dysfunction by upregulating the expression of the adhesion molecules ICAM-I and VCAM-I and the chemoattractants CCL-2, CXCL-8 and CXCL-1. IL-32-mediated expression of these chemokines was sufficient to drive monocyte transmigration in vitro. Finally, we demonstrate that IL-32 expression in both PLWH and controls correlates with the carotid artery stiffness, measured by the cumulated lateral translation. These results suggest a role for IL-32-mediated endothelial cell dysfunction in dysregulation of the blood vessel wall and that IL-32 may represent a therapeutic target to prevent CVD in PLWH.
慢性炎症与 HIV 感染者（PLWH）患心血管疾病（CVD）的风险增加有关。我们之前已经表明，白细胞介素-32（IL-32），一种多同种型促炎细胞因子，在 PLWH 中持续上调，并与 CVD 相关。然而，不同 IL-32 同种型在 CVD 中的作用机制仍有待确定。在这项研究中，我们旨在研究 IL-32 同种型对冠状动脉内皮细胞（CAEC）的潜在影响，CAEC 的功能障碍是动脉粥样硬化的主要因素。我们的研究结果表明，主要表达的 IL-32 同种型（IL-32β 和 IL-32γ）对 CAEC 产生促炎细胞因子 IL-6 具有选择性影响。此外，这两种同种型通过上调粘附分子 ICAM-I 和 VCAM-I 以及趋化因子 CCL-2、CXCL-8 和 CXCL-1 的表达来诱导内皮细胞功能障碍。IL-32 介导的这些趋化因子的表达足以在体外驱动单核细胞迁移。最后，我们证明 PLWH 和对照组中的 IL-32 表达与颈动脉僵硬度相关，通过累积侧向平移来测量。这些结果表明 IL-32 介导的内皮细胞功能障碍在血管壁失调中的作用，并且 IL-32 可能代表预防 PLWH 中 CVD 的治疗靶点。
