PTP1B in obesity-related cardiovascular function

Protein tyrosine phosphatase 1B (PTP1B), a molecular brake on leptin and insulin signaling pathways, is an important regulator of metabolic functions. Due to the close proximity between the signaling pathways regulating the metabolic and the cardiovascular systems, it has been hypothesized that PTP1B might have a role in the control of cardiovascular functions in the context of metabolic disorders. Evidence from population-based studies demonstrates that polymorphisms of the human PTP1B gene, PTPN1, predispose to both type II diabetes and cardiovascular disease, including hypertension and atherosclerosis. Consistent with these findings, genetic deletion of PTP1B in lean and obese animal models has proven to be protective against obesity-induced hypertension and endothelial dysfunction. While both human and animals studies mostly support indirect effects of PTP1B on the cardiovascular system via its control of metabolic function, evidence from in vitro studies suggests direct effects of PTP1B on endothelial and vascular smooth muscle cell integrity. Taken together these data identify PTP1B as a major regulator of cardiovascular function and suggest that manipulation of PTP1B expression and activity could provide a novel therapeutic approach to prevent obesity-related cardiovascular disease.