EcoHIV Infection Promotes Atherosclerosis Progression in LDLR-Deficient Mice.

Area of Science:

• Cardiovascular Science
• Virology
• Immunology

Background:

• People with HIV face increased risk of atherosclerotic cardiovascular disease (ASCVD).
• Molecular mechanisms linking HIV and ASCVD are poorly understood.
• Lack of suitable animal models hinders research.

Purpose of the Study:

• To investigate the impact of HIV on ASCVD pathogenesis.
• To establish a relevant animal model for HIV-associated cardiovascular disease.
• To explore molecular changes in atherosclerosis due to HIV infection.

Main Methods:

• Infection of atheroprone low-density lipoprotein receptor-deficient (Ldlr-/-) mice with chimeric HIV (EcoHIV).
• Analysis of inflammatory monocyte markers, recruitment, and lesion composition.
• Assessment of lesion vulnerability, necrotic core size, and collagen content.

Main Results:

• EcoHIV infection increased inflammatory monocytes and their recruitment to lesions.
• Lesions showed increased vulnerability, larger necrotic cores, and reduced collagen.
• Active EcoHIV replication was observed within atherosclerotic lesions.
• These changes occurred independently of plasma lipid profiles or lesion size.

Conclusions:

• EcoHIV infection in Ldlr-/- mice effectively models HIV-associated ASCVD.
• Findings highlight potential therapeutic targets for cardiovascular complications in people with HIV.
• This model provides a platform for developing interventions for HIV-infected individuals at high cardiovascular risk.