Inflammation and Cardiometabolic Diseases

Dr. Mehta’s research program focuses on the role of innate immunity and inflammation in the development of cardiovascular and metabolic diseases. Using a trans-disciplinary approach that involves genetic epidemiology, translational medicine, and novel cardiovascular imaging approaches, Dr. Mehta and his team study how inflammation affects insulin resistance, the development of metabolic syndrome, and lipoprotein dysfunction, all of which are risk factors for atherosclerosis and subsequent cardiovascular disease (CVD).

Dr. Mehta first became interested in this line of research following seminal studies demonstrating that inducing acute inflammation through exposure to lipopolysaccharide could induce insulin resistance in humans. To better understand the mechanism, Dr. Mehta utilized the chronic inflammation state observed in psoriasis, an inflammatory disease that visibly manifests as skin rashes to study the development of cardiometabolic diseases. Through a combination of laboratory, imaging, and clinical studies, Dr. Mehta helped shift the prevailing model of psoriasis, from thinking of it as just a skin disease to a disease of the whole body. His work has shown that people with psoriasis without CVD risk factors are at increased risk of CVD and future vascular events. Research from his lab has demonstrated that people with psoriasis display abnormal lipoprotein particle composition and impairment in high-density lipoprotein (HDL) efflux capacity, a measure of reverse cholesterol transport. Finally, utilizing his nuclear cardiology expertise, Dr. Mehta’s group was the first to utilize inflammatory imaging using positron emission tomography (PET) to demonstrate that patients with psoriasis have early onset of vascular disease and systemic inflammation. This imaging program has become a central outcome in several ongoing interventional studies in psoriasis to understand whether treatment of skin disease improves vascular disease. This core set of studies, called the Vascular Inflammation in Psoriasis (VIP), will lay the important foundation for future studies to understand whether treatment of inflammation may ameliorate vascular and metabolic diseases. 

To further understand the link between inflammation, atherosclerosis, and metabolic diseases, Dr. Mehta has joined the NHLBI to utilize the NIH Clinical Center to begin a comprehensive cardiometabolic phenotyping program. He sees patients with inflammatory diseases at the NIHCC for cardiovascular and metabolic risk assessment, and during that assessment obtains several tissues to characterize inflammatory states. These studies combined with high level multi-modal imaging by FDG PET/CT, FDG PET/MRI and coronary CT angiography will permit Dr. Mehta and his team to simultaneously measure pathways involved in atherosclerosis and metabolism to better understand how inflammation is associated with heart disease and diabetes. Dr. Mehta initiated the first large prospective cohort study of psoriasis (NCT017785690 to follow patients with this chronic inflammatory disease over several years to define CVD and metabolic pathways modulated in varying states of inflammation. Combined with imaging technology, this study will better inform patients and biology of how inflammation may lead to the development of cardiometabolic diseases.

The long term goals of Dr. Mehta’s lab are to improve both risk stratification and risk prediction for CVD in people with inflammatory conditions. He will continue to apply the diverse set of scientific approaches from his mechanistic translational science program to move discoveries from the bench to bedside, and understanding from the bedside back to the bench.