Endothelial dysfunction, arterial stiffening, and intima-media thickening in large arteries from HIV-1 transgenic...

Area of Science:

• Cardiovascular Science
• Virology
• Immunology

Background:

• Highly active antiretroviral therapy (HAART) and HIV infection are independent risk factors for cardiovascular disease (CVD), including atherosclerosis and myocardial infarction.
• Specific HIV proteins (tat, gp120, vpu, nef) are implicated in early-onset atherosclerosis.
• Elevated CVD incidence and subclinical atherosclerosis markers are observed in HIV patients on HAART.

Purpose of the Study:

• To investigate the role of HIV-1 protein expression in vascular function, biomechanics, and geometry of the common carotid arteries and aortas.
• To determine if HIV proteins, independent of HAART or HIV infection, contribute to CVD development.

Main Methods:

• Utilized NL4-3Δ gag/pol transgenic mice (HIV-Tg) expressing specific HIV-1 proteins (env, tat, nef, rev, vif, vpr, vpu) but lacking gag and pol genes.
• Assessed vascular function, including endothelial function, carotid artery intima-media thickness (c-IMT), and arterial stiffness.
• Analyzed arterial tissue for elastin content, cathepsin K and S activity, and mechanical residual stress.

Main Results:

• HIV-Tg mice exhibited impaired aortic endothelial function, increased c-IMT, and heightened arterial stiffness.
• HIV-Tg arteries demonstrated reduced elastin content, elevated cathepsin K and S activity, and increased mechanical residual stress.
• These findings indicate that HIV proteins alone can induce pre-clinical markers of atherosclerosis and vascular remodeling.

Conclusions:

• HIV proteins, independent of HAART or HIV infection, are implicated in the development of CVD.
• Expression of HIV proteins in mice leads to vascular dysfunction and geometric changes consistent with atherosclerosis.
• These results support the hypothesis that HIV proteins play a direct role in the pathogenesis of CVD.