Novel Molecular and Genetic Mechanisms of Arterial Calcification

Speaker: Rajeev Malhotra, MD MS

Host: Professor Cathy Shanahan

Location: Virtual seminar - join via this Teams Link.

Abstract

Vascular calcification is a hallmark of atherosclerotic disease and serves as a strong predictor and risk factor for cardiovascular events. Two primary types of vascular calcification occur: intimal calcification, associated with atherosclerosis, and medial calcification, associated with chronic kidney disease and diabetes. Intimal calcification occurs in the setting of lipid accumulation and macrophage infiltration into the vessel wall and is thought to contribute to plaque destabilization and predicts increased risk in cardiovascular disease. Calcification of the medial vessel layer also predicts cardiovascular events and is associated with increased wall stress, pulse pressure, heart failure, and risk of rupture in aortic aneurysms. Vascular calcification is a tightly regulated process and overlap exists in the molecular underpinnings of atherosclerotic intimal calcification and medial calcification. Using omics-based approaches to identify novel molecular mediators and pathways associated with both coronary and aortic calcification and both large vessel and small vessel disease, our laboratory investigates novel cellular and epigenetic regulators of vascular calcification and atherosclerotic heart disease. This talk will provide an overview of the clinical significance of arterial calcification. We will discuss matrix Gla protein (MGP) which is an important endogenous inhibitor of vascular calcification and arterial stiffness, as well as two protein families (Class IIa histone deacetylases and sulfatases) that are important mediators of arterial calcification with genetic underpinnings in human vascular disease. Lastly, we will discuss translational and clinical trial results for calciphylaxis, an accelerated form of arteriolar calcification with high morbidity and mortality.

Biography of Dr Rajeev Malhotra

Dr. Rajeev Malhotra graduated from Harvard College in chemistry and physics and obtained a master’s degree in chemistry and chemical biology from the Harvard Graduate School of Arts and Sciences. He received his medical degree from the Health Sciences and Technologies Division of Harvard Medical School and MIT. Dr. Malhotra completed residency in internal medicine and fellowship in general cardiology at the Massachusetts General Hospital. He then trained as a post-doctoral fellow with Dr. Kenneth Bloch, studying vascular biology. Dr. Malhotra serves as the Associate Program Director for the Cardiology Fellowship with a focus on mentoring fellows with their scholarly activities. Dr. Malhotra also serves as Associate Medical Director of the Cardiac Intensive Care Unit and Associate Director of the Cardiopulmonary Exercise Laboratory at Massachusetts General Hospital. He is a faculty member in the Cardiovascular Research Center and maintains an affiliation with the Broad Institute. His research interests include vascular biology, genetic and molecular mechanisms of atherosclerosis, pulmonary hypertension, and exercise physiology. Specifically, he investigates novel signaling pathways including epigenetic regulators, sulfatases, bone morphogenetic protein signaling, iron homeostasis, and autophagy in the development of vascular disease. In the cardiopulmonary exercise laboratory, Dr. Malhotra studies vascular response patterns to exercise in patients with heart failure and pulmonary hypertension. Dr. Malhotra has published over 130 research articles and his research has been supported by awards from the NIH, American Heart Association, American College of Cardiology, Massachusetts General Hospital, the Wild Family Foundation, the Hassenfeld Foundation, and Fast Grants.