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Arnold School of Public Health

Mark Sarzynski (EXSC) wins $3.4 million R01 grant to study impact of exercise on HDL particles

May 30, 2019 | Erin Bluvas, 

Exercise science assistant professor and director of the Foundations of Lipids and Exercise (FLEX) Laboratory Mark Sarzynski has been awarded $3.4 million from the National Institutes of Health’s National Heart, Lung, and Blood Institute. He will use the five-year R01 grant to examine the molecular basis of exercise-induced changes in high-density lipoprotein (HDL) function.  

HDL is often referred to as “good” cholesterol because HDL particles carry cholesterol from various parts of the body to the liver where the cholesterol is then removed. These HDL particles have many other cardiovascular protective functions – partly due to the molecular composition of the particles. Specifically, they inhibit vascular inflammation and reduce oxidative stress.

Researchers have observed that various diseases are accompanied by impaired HDL function and composition. Further, measures of HDL function serve as strong, independent predictors of cardiovascular disease risk.

Prior studies in the FLEX lab have also demonstrated that exercise training improves HDL function in a dose-specific manner. With Sarzynski’s new study, he will determine the amount and intensity (i.e., dose) and type (e.g., aerobic vs strength vs combination) of exercise that improves HDL function. He will also identify the molecules underlying these functional changes.

“Previous research suggests that HDL function is mediated by the molecules bound to HDL particles, which include proteins, lipids, and microRNAs,” Sarzynski says. “By identifying clinical and molecular predictors of exercise-induced changes in HDL function, we can help provide targeted exercise programs tailored to specific sex-race-disease groups to maximize the benefits.”

The study will utilize data from four large NIH-funded clinical exercise trials that have already been completed. By analyzing the data from more than 1,500 participants in these trials, Sarzynski and his team will examine how exercise amount, intensity and type affect three measures of HDL function (i.e., cholesterol efflux capacity, anti-inflammatory, anti-oxidant properties). They will also investigate whether the exercise effects on HDL function differ by race, sex, and/or metabolic profile (e.g., diabetes, metabolic syndrome, obesity).

In addition, the researchers will study the effects of exercise training on the HDL proteome, HDL lipidome, and HDL microRNA profiles and validate sex- and race-specific HDL molecular signatures that predict exercise-induced changes in HDL function. In parallel, they will integrate the generated HDL function and HDL composition data with available genomic, metabolomic, and muscle gene expression data to identify novel genes, pathways, and networks associated with exercise-induced changes in HDL function.

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