CCK1R2R-/- ameliorates myocardial damage caused by unpredictable stress via altering fatty acid metabolism
Zhi-Hua Zhang,
Chen-Teng Yang,
Xiao-Rui Su,
Ya-Ping Li,
Xiao-Jing Zhang,
Song-Jun Wang,
Bin Cong
Affiliations
Zhi-Hua Zhang
Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University
Chen-Teng Yang
Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University
Xiao-Rui Su
Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University
Ya-Ping Li
Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University
Xiao-Jing Zhang
Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University
Song-Jun Wang
Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University
Bin Cong
Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University
The heart is the main organ of the circulatory system and requires fatty acids to maintain its activity. Stress is a contributor to aggravating cardiovascular diseases and even death, and exacerbates the abnormal lipid metabolism. The cardiac metabolism may be disturbed by stress. Cholecystokinin (CCK), which is a classical peptide hormone, and its receptor (CCKR) are expressed in myocardial cells and affect cardiovascular function. Nevertheless, under stress, the exact role of CCKR on cardiac function and cardiac metabolism is unknown and the mechanism is worth exploring. After unpredictable stress, a common stress-inducing model that induces the development of mood disorders such as anxiety and reduces motivated behavior, we found that the abnormal contraction and diastole of the heart, myocardial injury, oxidative stress and inflammation of mice were aggravated. Cholecystokinin A receptor and cholecystokinin B receptor knockout (CCK1R2R-/-) significantly reversed these changes. Mechanistically, fatty acid metabolism was found to be altered in CCK1R2R-/- mice. Differential metabolites, especially L-tryptophan, L-aspartic acid, cholesterol, taurocholic acid, ADP, oxoglutaric acid, arachidonic acid and 17-Hydroxyprogesterone, influenced cardiac function after CCK1R2R knockout and unpredictable stress. We conclude that CCK1R2R-/- ameliorated myocardial damage caused by unpredictable stress via altering fatty acid metabolism.
