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Electrophilic Nitro‐Fatty Acids Exert Cardioprotection against Hypertrophic Remodeling and Fibrosis in Pressure Overloaded Mice
Author(s) -
Villacorta Luis,
Guo Yanhong,
Zhang Ji,
ConversoBaran Kimber,
Schopfer Francisco,
Freeman Bruce,
Chen Yuqing E.
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.640.6
Subject(s) - cardioprotection , fibrosis , medicine , cardiac function curve , pharmacology , muscle hypertrophy , pressure overload , cardiac fibrosis , cardiology , heart failure , ischemia , endocrinology , cardiac hypertrophy
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‐NO 2 ) is equally cardioprotective in hypertrophic remodeling. Cardiac hypertrophy were established in mice by transverse aortic constriction (TAC). Mice received either OA‐NO 2 , or OA as non‐nitrated fatty acid control. OA‐NO 2 delivery reduces hypertrophic remodeling and significantly reduces cardiac fibrosis compared to OA. Overall cardiac function, e.g. ejection fraction, is significantly improved by OA‐NO 2 . 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‐NO 2 delivery persistently confer cardioprotection indicating an alternative pathway for the improved cardiac function mediated by OA‐NO 2 . Rather, OA‐NO 2 primarily targets cardiac fibrosis and extracellular matrix gene expression profiles. Thus, protection against cardiac hypertrophic by nitro‐fatty acids via improving cardiac fibrosis supports further promise on nitro‐fatty acids derivatives as therapeutic agents for cardiovascular disease. Supported by the NIH (R01‐HL68878, R01‐HL058115, R01‐AT006822A), and the American Heart Association (10SDG4150085).