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HIV persists in late coronary atheroma and is associated with increased local inflammation and disease progression

Laventa M Obare1, Samuel S Bailin1, Xiuqi Zhang1

  • 1Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, USA.

Research Square
|November 1, 2024
PubMed

Insights

Chronic inflammation drives cardiovascular disease in people living with HIV (PLWH). This study found specific immune cell changes and gene expressions (ABCA1, CXCL12) linked to atherosclerosis in PLWH, offering potential therapeutic targets.

Area of Science:

  • Immunology
  • Cardiovascular Science
  • Infectious Disease

Background:

  • Chronic inflammation is a key factor in cardiovascular disease (CVD) among people living with HIV (PLWH).
  • The precise immune mechanisms underlying atherosclerosis progression in PLWH are not fully understood.

Purpose of the Study:

  • To investigate the immune mechanisms and molecular changes driving atherosclerosis in people living with HIV (PLWH).
  • To identify potential therapeutic targets for mitigating cardiovascular complications in PLWH.

Main Methods:

  • Comprehensive analysis of coronary arteries and aorta from deceased PLWH and controls using DNA/RNA assays, spatial transcriptomics, and mass spectrometry.
  • Examination of atherosclerotic phenotypes and inflammatory gene expression in a larger clinical cohort (Vanderbilt's Biobank).

Main Results:

  • Increased inflammation in atheroma correlated with higher HIV viral load in PLWH.
  • Co-localization of enhanced CXCL12 and decreased ABCA1/ABCG1 expression in CD163+ macrophages within PLWH coronaries, indicating impaired lipoprotein clearance.
  • Spatial analyses revealed inflammatory alterations in medium-sized arteries and aorta, identifying potential therapeutic targets.

Conclusions:

  • HIV significantly influences atherosclerosis development, partly through altered ABCA1 and CXCL12 gene expression.
  • Specific immune cell dysregulation and molecular pathways contribute to CVD risk in PLWH.
  • Findings provide insights into potential therapeutic strategies for cardiovascular health in PLWH.

Keywords:
ABCA1AtherosclerosisCD163CXCL12HIVcardiovascular disease

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