The natriuretic peptide system
The heart is an endocrine organ, secreting a family of hormones known as the natriuretic peptides. The classical actions of the natriuretic peptides are vasodilation and natriuresis, and the classical trigger of synthesis/secretion is increased cardiac wall stress. It is becoming increasingly apparent, however, that numerous extra-cardiac factors modulate natriuretic peptide activity. Further, there is growing evidence that the natriuretic peptides have diverse effects on metabolism and cardiovascular remodeling.
We study the influence of extra-cardiac factors on natriuretic peptides, both environmental and genetic, to understand how regulation of this axis affects cardiovascular health. A major focus is on the effects of obesity and weight loss on the natriuretic peptides, cardiac function, and physiologic responses to volume overload in both human and animal models. Our work has been published in major journals, including the New England Journal of Medicine, Circulation, JAMA, and Nature Genetics. Our natriuretic peptide studies involve extensive collaboration within the CVRC (Newton-Cheh laboratory, Bloch laboratory, Scherrer-Crosbie laboratory), the MGH Weight Center, the Endocrine Division, and other groups in Boston and nationally.
Metabolite profiling in large populations and physiologic studies
Our group has an active interest in the discovery of novel cardiometabolic biomarkers. We work closely with Dr. Gerszten’s laboratory in the CVRC on both large-scale metabolite profiling efforts (the Framingham Study and other, international cohorts) and profiling in well-defined physiologic samples at MGH. This work has led to enhanced understanding of metabolic alterations that may occur early in the evolution toward diabetes and hypertension, findings that could have both diagnostic and therapeutic applications. Our focus on novel biomarkers also includes work with cell-based biomarkers, conducted in collaboration with Dr. Shaw’s laboratory (CVRC and Center for Systems Biology).
Vitamin D and the heart
Vitamin D deficiency is highly prevalent worldwide. Although the best characterized sequelae of vitamin D deficiency involve the musculoskeletal system, a growing body of evidence suggests that low levels of vitamin D may adversely affect the cardiovascular system as well. Vitamin D receptors have a broad tissue distribution that includes vascular smooth muscle and endothelium. Vitamin D suppresses renin gene expression, regulates the growth of vascular smooth muscle cells, and inhibits cytokine release from lymphocytes. Disruption of vitamin D signaling in genetically-modified mice leads to elevated blood pressure and ventricular hypertrophy.
Our group is actively involved in epidemiologic, genetic, and physiologic studies aimed at understanding the effects of vitamin D on the cardiovascular system. Recent studies from our group in this area have been published in the Lancet and Circulation. Dr. Wang also co-chairs a large, international genetic consortium on vitamin D (SUNLIGHT).
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