Electrophilic Nitro-Fatty Acids Exert Cardioprotection against Hypertrophic Remodeling and Fibrosis in Pressure Overloaded Mice

Electrophilic nitro-fatty acids, the nitration products of unsaturated fatty acids are generated in cardiomyocytes after ischemia/reperfusion injury and protects against myocardial infarction. Herein, we determine whether nitro-oleic acid (OA-NO2) is equally cardioprotective in hypertrophic remodeling. Cardiac hypertrophy were established in mice by transverse aortic constriction (TAC). Mice received either OA-NO2, or OA as non-nitrated fatty acid control. OA-NO2 delivery reduces hypertrophic remodeling and significantly reduces cardiac fibrosis compared to OA. Overall cardiac function, e.g. ejection fraction, is significantly improved by OA-NO2. Electrophilic signiling through Nrf2 is a plausible mechanism of cardioprotection by nitroalkenes. However, in Nrf2 knockout mice, which develop exacerbated cardiac hypertrophy after TAC, OA-NO2 delivery persistently confer cardioprotection indicating an alternative pathway for the improved cardiac function mediated by OA-NO2. Rather, OA-NO2 primarily targets car...