Identification of metabolic pathways underlying FGF1 and CHIR99021-mediated cardioprotection
Bing Xu,
Fan Li,
Wenjing Zhang,
Yajuan Su,
Ling Tang,
Pengsheng Li,
Jyotsna Joshi,
Aaron Yang,
Dong Li,
Zhao Wang,
Shu Wang,
Jingwei Xie,
Haiwei Gu,
Wuqiang Zhu
Affiliations
Bing Xu
Department of Cardiovascular Diseases, Physiology and Biomedical Engineering, Center for Regenerative Medicine, Mayo Clinic Arizona, 13400 E Shea Blvd, Scottsdale, AZ, USA 85259; Department of Cardiology, Northern Jiangsu People’s Hospital, Clinical Medical College, Yangzhou University, Yangzhou 225001, China
Fan Li
Department of Cardiovascular Diseases, Physiology and Biomedical Engineering, Center for Regenerative Medicine, Mayo Clinic Arizona, 13400 E Shea Blvd, Scottsdale, AZ, USA 85259; Department of Kinesiology, South China Normal University, Guangzhou 510631, China
Wenjing Zhang
Center for Translational Science, Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Port St. Lucie, FL 34987, USA; College of Health Solutions, Arizona State University, Phoenix, AZ 85287, USA
Yajuan Su
Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA
Ling Tang
Department of Cardiovascular Diseases, Physiology and Biomedical Engineering, Center for Regenerative Medicine, Mayo Clinic Arizona, 13400 E Shea Blvd, Scottsdale, AZ, USA 85259
Pengsheng Li
Department of Cardiovascular Diseases, Physiology and Biomedical Engineering, Center for Regenerative Medicine, Mayo Clinic Arizona, 13400 E Shea Blvd, Scottsdale, AZ, USA 85259
Jyotsna Joshi
Department of Cardiovascular Diseases, Physiology and Biomedical Engineering, Center for Regenerative Medicine, Mayo Clinic Arizona, 13400 E Shea Blvd, Scottsdale, AZ, USA 85259
Aaron Yang
Department of Cardiovascular Diseases, Physiology and Biomedical Engineering, Center for Regenerative Medicine, Mayo Clinic Arizona, 13400 E Shea Blvd, Scottsdale, AZ, USA 85259
Dong Li
Department of Cardiovascular Diseases, Physiology and Biomedical Engineering, Center for Regenerative Medicine, Mayo Clinic Arizona, 13400 E Shea Blvd, Scottsdale, AZ, USA 85259
Zhao Wang
Department of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
Shu Wang
College of Health Solutions, Arizona State University, Phoenix, AZ 85287, USA
Jingwei Xie
Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA
Haiwei Gu
Center for Translational Science, Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Port St. Lucie, FL 34987, USA; College of Health Solutions, Arizona State University, Phoenix, AZ 85287, USA; Corresponding author
Wuqiang Zhu
Department of Cardiovascular Diseases, Physiology and Biomedical Engineering, Center for Regenerative Medicine, Mayo Clinic Arizona, 13400 E Shea Blvd, Scottsdale, AZ, USA 85259; Corresponding author
Summary: Acute myocardial infarction is a leading cause of death worldwide. We have previously identified two cardioprotective molecules — FGF1 and CHIR99021— that confer cardioprotection in mouse and pig models of acute myocardial infarction. Here, we aimed to determine if improved myocardial metabolism contributes to this cardioprotection. Nanofibers loaded with FGF1 and CHIR99021 were intramyocardially injected to ischemic myocardium of adult mice immediately following surgically induced myocardial infarction. Animals were euthanized 3 and 7 days later. Our data suggested that FGF1/CHIR99021 nanofibers enhanced the heart’s capacity to utilize glycolysis as an energy source and reduced the accumulation of branched-chain amino acids in ischemic myocardium. The impact of FGF1/CHIR99021 on metabolism was more obvious in the first three days post myocardial infarction. Taken together, these findings suggest that FGF1/CHIR99021 protects the heart against ischemic injury via improving myocardial metabolism which may be exploited for treatment of acute myocardial infarction in humans.
