Sanjeev G. Shroff, PhD

302 Benedum Hall | 3700 O’Hara Street | Pittsburgh, PA 15261 P: 412-624-2095

sshroff@pitt.edu Chair

Distinguished Professor of and McGinnis Chair in Bioengineering

Professor of Medicine

Cardiovascular Systems Laboratory

Our research interests are focused on three areas: (1) Relationships between left ventricular mechano-energetic function and underlying cellular processes, with a special emphasis on contractile and regulatory proteins and post-translational regulation of cardiac contraction (e.g., via phosphorylation or acetylation). Whole heart, isolated muscle (intact and detergent-skinned), and single cell experiments are performed using various animal models, including transgenic mice. (2) The role of pulsatile arterial load (vascular stiffness in particular) in cardiovascular function and potential therapeutic applications of vascular stiffness-modifying drugs and/or hormones (e.g., relaxin). Novel noninvasive measurement techniques are used to conduct longitudinal human studies, which are complemented by in vivo and in vitro vascular and cardiac studies with animal models. (3) The role of regional contraction dyssynchrony in global ventricular mechanics and energetics. In addition to basic research, we work on developing novel mathematical models of biological systems for scientific inquiry, education, and engineering design. Two ongoing research projects are described below.

Post-translational Regulation of Cardiac Muscle Contraction

Phosphorylation-mediated regulation of cardiac muscle contraction has been studied extensively. Our group has been focusing on cardiac Troponin I (cTnI), especially the effects of PKA- vs. PKC-mediated cTnI phosphorylation on cardiac contraction under normal and pathological conditions.1,2 In collaboration with the Gupta laboratory (University of Chicago), we discovered a completely new post-translational modification, myofilament protein acetylation, that can regulate cardiac muscle contraction as potently as phosphorylation (acetylation ==>  myofilament calcium sensitivity for force generation).3,4 Experiments are currently underway to determine the biophysical mechanisms responsible for this novel contractile regulation and to examine its physiological significance under in vivo conditions. This basic science information regarding the post-translational regulation of contraction is being used to develop novel inotropic therapies.

Role of Relaxin in the Cardiovascular System

Our group has been working on examining the role of relaxin, traditionally considered to be a pregnancy-associated hormone, in the cardiovascular system. We have shown that exogenous relaxin administration produces significant vasodilation ( systemic vascular resistance) and vasorelaxation ( global arterial compliance) in both male and female animals.5 Furthermore, relaxin-1 and its receptor mRNA are expressed in vascular tissues obtained from various mammals of both sexes, leading us to propose that the relaxin ligand-receptor system acts locally to regulate arterial function and the loss of one or both of these components may form the molecular basis of vascular aging.6 We and others have shown that relaxin is a potent anti-fibrotic agent. In collaboration with the Salama laboratory (University of Pittsburgh), we recently showed that relaxin administration completely suppressed induced atrial fibrillation in aged spontaneously hypertensive rats and both the reversal of myocardial fibrosis and an increase in myocyte sodium current contributed to this suppression.7 Current studies are aimed at further examining the therapeutic potential of relaxin in fibrosis-associated cardiovascular diseases (e.g., diastolic heart failure, atrial fibrillation).

1. MacGowan G, et al. Cardiovasc Res. 63:245-255, 2004. 2. Kirk JA, et al. Circ Res. 105:1232-1239, 2009. 3. Gupta MP, et al. J Biol Chem. 283 (15):10135-10146, 2008. 4. Samant SA, et al. J Biol Chem. 290:15559-15569, 2015. 5. Conrad KP, Shroff SG. Curr Hypertens Rep. 13:409-420, 2011. 6. Novak J, et al. FASEB J. 20:2352-2362, 2006. 7. Parikh A, et al. Circ Res. 113:313-321, 2013.