Plasma protein markers of the blood pressure response during exercise and their relation to incident hypertension and cardiovascular disease - PROJECT SUMMARY/ABSTRACT This project addresses the limitations of current cardiovascular disease (CVD) risk assessment methods, which primarily depend on measurements taken at rest. These traditional methods often fail to unveil hidden cardiovascular risks that become apparent only under conditions of physiological stress, such as during acute exercise. Acute exercise serves as a pivotal tool in this context, offering a more comprehensive assessment of cardiovascular health. One particularly valuable measurement acquired during exercise that is highly predictive of disease is the blood pressure response during exercise (exercise BP). However, the molecular characterization of exercise BP remains unknown. In human data, the applicant has identified circulating proteins related to exercise BP that are also linked to future hypertension risk. Importantly, the vast majority of these proteins would not have been identified through profiling of resting BP alone. The applicant will now expand upon these pilot findings using antibody-based plasma proteomics capable of measuring ~5000 unique protein targets. The applicant will test whether specific proteins are associated with exercise BP in two distinct exercise cohorts (Aim 1). The applicant will then assess the broader clinical implications of these protein markers of exercise BP by examining their associations with incident hypertension and CVD in large cohorts of diverse racial/ethnic backgrounds, and testing whether genetically predicted levels of these proteins are also associated with CVD outcomes (Aim 2). The applicant will integrate relevant findings in animal model systems to unveil the specific cell types and organ systems that secrete these proteins into the circulation (Aim 3). Finally, the applicant will test whether protein signatures of exercise BP among patients with heart failure with preserved ejection fraction [HFpEF] correlate with exercise capacity and markers of disease severity and whether they are modifiable by cardiac rehabilitation (Aim 4). The applicant is an early career investigator and cardiologist with a research focus on leveraging cutting-edge biochemical profiling techniques to characterize individual responses during exercise. This proposal will further the applicant’s career development through training in exercise physiology, state-of-the-art proteomics, advanced biostatistical methods, animal model systems, and the conduct of patient-oriented research. The applicant will be supported by an exceptional team of senior investigators renowned for their mentoring achievements and expertise in exercise physiology, human proteomics, genetic epidemiology, and translational research using animal models. This team will guide the applicant as he transitions to research independence during the award.
