Phone: (914) 594-4123/4122
Department of Pharmacology
Basic Science Building, Rm. 501
15 Dana Road
Valhalla, NY 10595
Our research is focused on two major areas: 1) the regulation of coronary collateral growth, and 2) the mechanisms by which metabolic syndrome effects systemic macro- and microvascular function.
Regulation of coronary collateral growth
Coronary collateral growth (CCG), an adaptive process to transient, repetitive myocardial ischemia characteristic of angina pectoris is severely compromised in metabolic syndrome resulting in greater incidence and severity of myocardial infarctions and higher mortality in this patient population. The aim of our studies is to elucidate signaling pathways and cellular processes which are necessary and sufficient for coronary collateral formation in normal, healthy animals, and determine how they are altered in metabolic syndrome in order to develop treatment paradigms to restore CCG in metabolic syndrome. We have identified several key mediators of impaired CCG in the metabolic syndrome to date, including: oxidative stress, increased 20-HETE, down regulated miR-145 expression and consequent altered vascular smooth muscle (VSM) phenotype, matrix metalloproteinase activation and aberrant extracellular matrix (ECM) remodeling. Current work focuses on how restoration of normal 20-HETE and mir-145 levels and VSM phenotype to the normal adult contractile phenotype leads to complete restoration of CCG and controls critical regulatory aspects of CCG including ECM modulation, endothelial function and inflammation.
Effect of Metabolic Syndrome on Vascular Function
In these projects we are attempting to isolate the contribution of specific components of the metabolic syndrome vs. the composite syndrome on vascular function and structure and VSM phenotype with the goal of designing patient-specific and, thus, more effective therapies for prevention of end-stage cardiovascular complications of metabolic syndrome. Current work focuses on finding which metabolites (ex. 20-HETE) and signaling intermediates (MMP12) released from expanded intra-abdominal (visceral) adipose tissue of metabolic syndrome animal models and patients, are critical determinants of altered VSM phenotype and compromised macro- and microvascular function in metabolic syndrome.