Differential Impact of IL-32 Isoforms on the Functions of Coronary Artery Endothelial Cells: A Potential Link with Arterial Stiffness and Atherosclerosis

Rémi Bunet, Marie Hélène Roy-Cardinal, Hardik Ramani, Aurélie Cleret-Buhot, Madeleine Durand, Carl Chartrand-Lefebvre, Jean Pierre Routy, Réjean Thomas, Benoît Trottier, Petronela Ancuta, David B. Hanna, Alan L. Landay, Guy Cloutier, Cécile L. Tremblay, Mohamed El-Far

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number700
JournalViruses
Volume15
Issue number3
DOIs
StatePublished - Mar 2023
Externally publishedYes

Keywords

  • arterial stiffness
  • cardiovascular disease
  • CCL-2
  • CXCL-1
  • CXCL-8
  • endothelial cell dysfunction
  • HIV
  • IL-32
  • inflammation

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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