Background: People with HIV are at higher risk of atherosclerotic cardiovascular disease than uninfected individuals; however, the molecular mechanisms behind this association remain elusive due to the lack of suitable animal models.
Methods: To study the impact of HIV on atherosclerotic cardiovascular disease, we infected the atheroprone Ldlr-/- mice with the chimeric virus EcoHIV.
Results: In comparison to uninfected controls, EcoHIV infection increased the ratio of circulating inflammatory monocytes, monocyte recruitment, and CD68+ content in the atherosclerotic lesion. These changes occurred independently of alterations in plasma lipid profile or lesion size between groups. Lesions of EcoHIV-infected mice displayed greater vulnerability to rupture, as determined by increased necrotic core area and CD38+ content, and reduced presence of collagen compared with uninfected mice. Last, we report the presence of active viral replication of EcoHIV in the atherosclerotic lesion.
Conclusions: Our data suggest that EcoHIV infection in Ldlr-/- mice resembles the pathogenesis of atherosclerotic cardiovascular disease in people with HIV. Our findings have therapeutic implications for people with HIV, a vulnerable population with an elevated risk of cardiovascular disease.
Keywords: acquired immunodeficiency syndrome; cardiovascular diseases; inflammation; macrophages; myocytes, smooth muscle.