Cardiovascular disease (CVD) remains a significant cause of morbidity and mortality in HIV patients despite the advances in early diagnosis and treatment. HIV infection leads to a 1.5 to 2x greater increase in cardiovascular disease risk compared to non-infected populations. While Native Hawaiians and Other Pacific Islanders (NHOPI) represent 0.4%t/ of the total population in the United States, the HIV case rate for NHOPI was twice that of the White population in 2014. NHOPI with HIV are over 3x more likely to be hospitalized than Whites with HIV. This is likely to compound CVD risk in this minority population. Monocyte/macrophage (MO) plays an essential role in the formation of atherosclerotic plaque. Although it is known that HIV infects monocytes it is not known whether HIV infection alters the atherogenic properties of macrophages. We hypothesize that MO dysregulation is a critical aspect of HIV immune dysregulation responsible for the increased development of atherosclerosis in this population. To elucidate this, we will perform a cross- sectional comparison of MO function in HIV+ individuals including NHOPI on suppressive antiretroviral therapy (ART) and 72 HIV-uninfected individuals of similar age, gender, and ethnic and socio-demographic composition. The MO functions we will measure are: (1) monocyte inflammatory cytokine production, (2) trans- endothelial migration capacity of monocytes, (3) macrophage cholesterol uptake/ foam cell formation (4) macrophage cholesterol efflux, and (5) intracellular monocyte HIV DNA and RNA level. These parameters will then be compared to the carotid intimal thickness (CIMT) measurements from each of the subjects in an attempt to find associations between MO function and extent of atherosclerosis in each of the populations.
The specific aims to be performed in this proposal are:
Specific Aim I : To compare inflammatory profiles and trans- migration capacity of monocytes isolated from HIV-infected individuals on suppressive ART and HIV non- infected individuals and correlate these parameters with carotid intimal thickness (CIMT) as a marker of atherosclerosis;
SPECIFIC AIM II : To assess if differences in macrophage lipid metabolism patterns contribute to increased atherosclerotic burden amongst HIV-infected individuals;
and SPECIFIC AIM III : To associate intracellular monocyte HIV DNA and RNA level with atherosclerotic burden among HIV-infected individuals on suppressive ART. The innovation of this proposal lies in the ability to link sophisticated laboratory data to provide meaningful data on how monocyte function relates to CVD in the context of HIV. This study will utilize the Research Infrastructure Core which includes resources from Biostatistics Support and Clinical Research Support Facilities. In addition, the study will work with the Community Engagement Core resources to enhance the quality of this translational research, which will result in the enhancement of the UHM?s research capacity within the areas of basic biomedical and clinical research.
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