Exploring a Novel Atheroprotective Role of FFAR4

Project Summary:

Cardiovascular disease (CVD), encompassing coronary heart disease, hypertension and stroke, is the leading cause of death among Americans across all racial and ethnic groups. Importantly, it is the primary cause of death--surpassing all cancers combined--and accounted for over 31% of all deaths in the U.S. in 2019. In 2023, 12,999 people in Wisconsin alone died of CVD, representing 22% of deaths in the state. Apart from being a major health issue, CVD is also a major economic burden to the people of Wisconsin. 2023 saw over $5.7 billion in hospital-related expenditures related to CVD-related care. This economic strain, combined with mortality, clearly shows that more CVD research is absolutely required to reduce and reverse these alarming trends in Wisconsin and in the nation. Lipid-lowering therapies (e.g., statins) have been used as a strategy to prevent cholesterol from accumulating in the blood and have proved successful in improving survival of patients post-heart attack. However, such therapies may result in adverse side effects and residual CVD risk (i.e., heart attacks can still occur). As such, there is a need to devise strategies to prevent the various stages of atherosclerosis. Building on recent findings, the project team presents an alternative approach to reducing CVD risk and their project is designed to test the hypothesis that FFAR4 plays a cardioprotective role by limiting the formation of necrotic cores in atherosclerotic lesions. The outcomes of these proposed studies will provide scientific premise for broader mechanistic studies of FFAR4 through future NIH R01 funding and may identify FFAR4 as a therapeutic target against atherosclerosis. Most importantly, the long-term benefits of these proposed experiments translate directly to improved life expectancy and quality of life of patients at risk of CVD and reducing the financial burden on Wisconsin taxpayers.