Nothing Micro About It: Investigating the Role of miRNAs and Cannabis Use in Cardiac Dysfunction among People Living with HIV - PROJECT SUMMARY Overview. This dissertation research study proposes to examine epigenetic profiles of cardiac dysfunction in people with HIV (PWH) who use and do not use cannabis. Specifically, we will examine microRNA (miRNA) profiles of cardiac dysfunction, and investigate how cannabis use, and its metabolites (e.g., CBD and THC), may alter these profiles. Significance. HIV-associated non-AIDS conditions such as cardiovascular disease (CVD) are increasingly prevalent among PWH. Evidence suggests that PWH have increased rates of CVD and earlier onset that may be attributable to traditional risk factors (including substance use), chronic inflammation and immune activation, and antiretroviral therapy regimens. Additionally, cannabis use is prevalent among PWH and may be associated with increased risk for cardiac dysfunction. However, scant research has been done to examine cannabis associated alterations in CVD risk among PWH, and even less has examined cannabis use metabolites’ role. miRNAs, which are non-coding RNAs that regulate gene expression, are integral to the development and (dys)function of the cardiovascular system. They may also represent a novel upstream biomarker of pre-clinical CVD risk. However, little is known about how cannabis use, its metabolites, and HIV may alter miRNA profiles and contribute to alterations relevant to cardiac dysfunction. Objectives & methods. Thus, this R36 dissertation research project will leverage extant samples to gain a better understanding of miRNA profiles relevant to cardiac dysfunction in PWH, and investigate how cannabis use (including dose-response associations with cannabis use metabolites) may alter this relationship. Aim 1 will characterize the association of miRNA profiles with cannabis use (versus no cannabis use) in PWH. Aim 2a will examine the association of miRNA profiles with a measure of cardiac dysfunction in PWH who use and do not use cannabis. Aim 2b will then determine the dose-response associations of CBD and THC metabolite levels with miRNA profiles and a measure of cardiac dysfunction among PWH that use cannabis. Samples for miRNA profiling will be used from an ongoing NIDA DP2 Avenir Award that is collecting demographic and HIV clinical information, and a measure of cardiac dysfunction (cardiac MRI with fast-strain-encoded imaging). miRNA profiles will be generated from next generation sequencing of stored whole blood samples of N = 100 PWH (n = 50 who use cannabis, and n = 50 who do not use cannabis). Innovation. This dissertation research proposal is among the first to examine the potential association of miRNA profiles with subclinical cardiac dysfunction among PWH. It will also leverage a novel measure of cardiac dysfunction, and next generation sequencing to characterize cardiac miRNA profiles. Findings from this proposal will provide foundation experience relevant to my goal of pursuing a career as a molecular epidemiologist with expertise in co-occurring HIV, CVD, and substance use.
