University of Alabama at Birmingham Division of Cardiovascular Disease have been awarded a $3.7 million grant from the National Heart Lung and Blood Institute to study how genetically determined differences in natriuretic peptide levels (heart hormones) regulate the handling of glucose metabolism and use of energy while resting and while exercising.Researchers from the
The grant is being used to fund a first-of-its-kind clinical trial that will recruit healthy individuals through a “genome-first” approach and perform deep metabolic phenotyping to understand the underlying mechanisms responsible for the regulation of the body’s metabolism through NPs.
NPs are hormones produced by the heart that regulate cardiometabolic health. These hormones are released in response to changes in pressure inside the heart. These hormones are also responsible for regulating how the body responds to glucose and how it utilizes energy at rest and while working out.
Pankaj Arora, M.D., associate professor of medicine and the director of the $11 million NIH-funded Cardiovascular Clinical and Translational Research Program and the UAB Cardiogenomics Clinic, received the grant.
An estimated 37 million adults in the United States have diabetes, and an additional 96 million adults have pre-diabetes, which predisposes them to a higher risk of potentially fatal cardiovascular events such as heart attack, stroke and heart failure.
Researchers believe that genetically determined low NP levels may contribute to some individuals’ having a poor glucose metabolism and a low amount of any exercise. Individuals with lower circulating NP levels are predisposed to a higher risk of cardiometabolic diseases such as diabetes, high blood pressure, heart attacks, stroke and heart failure.
“The study is employing an innovative ‘genome-first’ strategy to assess the role of NPs in regulating the cardiovascular and metabolic health of an individual,” Arora said. “We will be enrolling individuals with and without a common genetic variant that predisposes them to have low NP levels. The study participants will then undergo a comprehensive metabolic assessment to understand the influence of genetically determined low NP levels.”
The study is the result of decades of interdisciplinary research conducted by UAB scientists in collaboration with investigators across the country. Through past research, Arora and colleagues have shown that certain RNA-based regulators control the production of NPs and serve as potential therapeutic targets. Arora and his colleagues are studying how these regulators can be targeted for a precision medicine approach to the treatment of common cardiometabolic diseases.
“There are certain RNA-based regulators that control the production of these good heart hormones that were discovered by our group of researchers,” Arora said. “These regulators reduce the production of NPs in individuals with a low NP genotype and may serve as potential therapeutic targets for the treatment of high blood pressure, diabetes, pre-diabetes and heart failure.”
In addition to an innovative “genome-first” approach, the study by Arora and colleagues may also unravel a potentially new line of personalized therapeutics that follow the same “genome-first” precision medicine approach.
Arora believes that innovative studies like these build upon the advances in genomic medicine and bring the knowledge of decades of research back to the benefit of the patients at their bedside. UAB has been supporting such “bench-to-bedside” initiatives that translate scientific evidence accumulated from large-scale population genomic studies and bench research to the patient bedside. UAB physician-scientists are leading several such initiatives to enhance clinical and translational research in the domains of cardiometabolic disease.