Proteomic profiling of heart failure in Hispanics/Latinos

ABSTRACT Heart failure (HF) cases are projected to increase steadily in the next decade given the aging population. Inflammation is one pathophysiological feature of HF. Several direct anti-inflammatory therapies are designed for HF; however, none has been proven to demonstrate convincing benefits. Hispanic Americans have high rates of HF comorbidities, i.e., obesity and diabetes, key drivers of systemic inflammation, specifically for HF with preserved left ventricular ejection fraction (HFpEF), a subtype without efficacious therapies. A few inflammatory biomarkers have been identified reflecting HF comorbidities; the molecular pathways leading to cardiac dysfunction, and ultimately HFpEF, are uncertain. Racial disparities have been observed in HF, however, data from Hispanic/Latino populations are sparse. In addition, acculturation and socioeconomic factors can promote inflammation, contributing to the abnormalities of cardiac structure and function. Lack of understanding of the biologic pathways underlying cardiac dysfunction and development of HF is a critical barrier to developing effective interventions to prevent HF, specifically in Hispanics/Latinos. We propose to perform state-of-art proteome profiling in the NHLBI-sponsored Hispanic Community Health Study / Study of Latinos (HCHS/SOL), the most comprehensive study of Hispanic/Latino health and disease to identify protein biomarkers associated with cardiac dysfunction and HF risk. Our central hypothesis is that proteins, specifically reflecting systematic inflammation, will be causally associated with cardiac structure and function, as well as the risk of HF. In Aim 1, we will identify circulating proteins and protein signatures associated with impaired cardiac functions and their progression. In Aim 2, we will identify circulating proteins and protein signatures that predict the development of clinical HF. In both aims, we will further investigate the effect of identified protein signatures on acculturation, socioeconomic and lifestyle factors. In Aim 3, we will identify genetic determinants of HF- and cardiac function- related proteins, and determine the extent to which genetic variations relate to cardiac dysfunction and clinical HF. With the completion of this project, we aim to generate insights into the biological pathways underlying progressive cardiac dysfunction and HF, and to provide targets for drug development.