Ischemic heart disease is a leading cause of death in both men and women in the United States. Research in the Kohr Laboratory of Cardiovascular Redox Signaling seeks to identify novel, redox-dependent biological mechanisms that reduce ischemic injury in the heart. Current projects center on the protective role of myocardial protein S-nitrosation, with a major focus on sex-specific differences. The female heart is of particular interest, since it is naturally protected from ischemic injury. To investigate these protective mechanisms, we have developed a number of cutting-edge mass spectrometry-based proteomic methodologies to map sites of S-nitrosation and other redox-based modifications, and we use these in tandem with cellular, molecular, and biochemical methods to assess the effects of S-nitrosation on the function, stability, and localization of specific protein targets. We also utilize a number of physiological approaches to evaluate myocardial function, including the Langendorff-perfused heart preparation, in vivo pressure-volume loop analysis, and echocardiography. Additional projects seek to evaluate the impact of environmental toxicants (i.e., arsenic) on myocardial physiology and cardioprotective signaling. By defining female-specific and other protective signaling pathways in the heart, and assessing the potential environmental impact on these pathways, we seek to identify key therapeutic targets for the treatment of ischemic heart disease in both men and women.