BIOSKETCH AND RESEARCH INTERESTS
Dr. Pankaj Arora, MD, FAHA, is a physician scientist in the Division of Cardiovascular Disease with expertise in the human genetics and genomics of complex cardiovascular traits, as well as physiological validation of newly-identified genes associated with these traits. Dr. Arora has extensive prior experience working as a research fellow at the Framingham Heart Study, as a clinical research fellow at the Massachusetts General Hospital, and as an affiliate scientist at Broad Institute of Harvard & MIT.
Dr. Arora’s current genetic efforts are focused on studying genetic basis of natriuretic peptide levels in population cohorts such as REGARDS, and he has been recognized by Cardiology Today as a NextGen Innovator. Dr. Arora’s laboratory is actively working with HudsonAlpha faculty investigator Devin Absher, PhD, on dissecting the molecular mechanisms behind racial differences in natriuretic peptide levels. Dr. Arora’s long-term goal is primarily to translate genetic discoveries into an improved understanding of human physiology through clinically-focused research.
Dr. Arora is presently funded by the Department of Medicine's Walter B. Frommeyer Jr. Fellowship in Investigative Medicine. Dr. Arora’s group is conducting a human physiologic study in the clinical research unit to determine whether Atrial natriuretic peptide (ANP) changes in response to a high-carbohydrate meal in blacks and whether there is a difference in the magnitude of change in ANP in African Americans vs. Caucasians. Considerable efforts from Dr. Arora are focused on conducting clinical outcomes research as well.
On a national level, Dr. Arora is the past Chair and currently serves as the Faculty Advisor of the Early Career Committee of Functional Genomics and Translational Biology Council at the American Heart Association. Dr. Arora is also a member of the search committee designed to find the editor in-chief of Circulation: Cardiovascular Genetics. Dr. Arora is actively involved in reviewing Grants for the American Heart Association and the Precision Medicine Institute of AHA.
ABSTRACT
Background. The cardiac natriuretic peptides (NPs), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), have central roles in sodium and blood pressure regulation. Extracardiac factors (e.g., obesity and diabetes) influence NP production, potentially altering cardiovascular responses to volume and pressure stress.
Objectives. This study examined the effects of acute carbohydrate intake on the NP system in humans, and investigated underlying mechanisms.
Methods. Normotensive subjects (N = 33) were given a high-carbohydrate shake. Venous blood was sampled to measure N-terminal (NT)-proANP and NT-proBNP levels. Human embryonic stem cell–derived cardiomyocytes (hESC-CMs) and HepG2 cells were treated with glucose, and expression levels of NPs and micro ribonucleic acid 425 (miR-425), a negative regulator of ANP, were examined. The role of nuclear factor kappa B (NF-kB) in the glucose-mediated effects was investigated using a NF-kB inhibitor and expression plasmids encoding NF-kB subunits.
Results. We observed a 27% reduction in the levels of circulating NT-proANP (p < 0.001, maximal at 6 h) after carbohydrate challenge, with no effect on NT-proBNP levels in our human subjects. Glucose treatment of hESC-CMs for 6 h and 24 h increased levels of the primary transcript of miR-425 (pri-miR-425) and mature miR-425. A corresponding decrease in NPPA messenger RNA levels was also observed at both time points. Overexpression of NF-kB subunits in H9c2 cardiomyocytes increased miR-425 levels, whereas inhibition of NF-kB abrogated the glucose-mediated increase in pri-miR-425 levels in HepG2 cells.
Conclusions. Acute carbohydrate challenge is associated with a reduction in ANP production. The mechanism appears to involve a glucose-induced increase in the expression of miR-425, mediated by NF-kB signaling.