Cholesterol efflux in HIV-associated atherosclerosis: mechanisms and targets

Area of Science:

• Biomedical Science
• Cardiovascular Research
• Infectious Disease

Background:

• Antiretroviral therapy (ART) has made HIV infection a chronic condition.
• People living with HIV (PLWH) face elevated risks of atherosclerotic cardiovascular disease (ASCVD).
• Impaired cholesterol efflux from macrophages and dysfunction of high-density lipoprotein (HDL) contribute to HIV-associated atherosclerosis.

Purpose of the Study:

• To explore the molecular mechanisms underlying HIV-induced cholesterol efflux impairment.
• To review emerging therapies for targeting ASCVD risk in PLWH.

Main Methods:

• Review of molecular mechanisms of HIV-Nef protein's impact on ATP-binding cassette transporter (ABC)A1.
• Analysis of how ART affects macrophage and HDL function.
• Exploration of novel therapeutic strategies targeting reverse cholesterol transport.

Main Results:

• HIV Nef protein inhibits ABCA1-mediated cholesterol efflux through post-transcriptional downregulation, mislocalization, and degradation.
• ART partially restores macrophage and HDL function but persistent cholesterol efflux impairment is observed.
• Emerging therapies show promise in enhancing reverse cholesterol transport and reducing HIV replication.

Conclusions:

• Persistent cholesterol efflux impairment in PLWH on ART contributes to elevated ASCVD risk.
• Novel therapeutic approaches targeting reverse cholesterol transport and HIV replication are crucial for managing ASCVD in PLWH.