TY - JOUR
T1 - CYP2J deficiency leads to cardiac injury and presents dual regulatory effects on cardiac function in rats
AU - Zhang, Yanfang
AU - Lu, Jian
AU - Huang, Shengbo
AU - Zhang, Yuanjin
AU - Liu, Jie
AU - Xu, Yuan
AU - Yao, Bingyi
AU - Wang, Xin
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/8/15
Y1 - 2023/8/15
N2 - Cytochrome P450 2J2 (CYP2J2) enzyme is widely expressed in aortic endothelial cells and cardiac myocytes and affects cardiac function, but the underlying mechanism is still unclear. Based on CYP2J knockout (KO) rats, we have directly studied the metabolic regulation of CYP2J on cardiac function during aging. The results showed that CYP2J deficiency significantly reduced the content of epoxyeicosatrienoic acids (EETs) in plasma, aggravated myocarditis, myocardial hypertrophy, as well as fibrosis, and inhibited the mitochondrial energy metabolism signal network Pgc-1α/Ampk/Sirt1. With the increase of age, the levels of 11,12-EET and 14,15-EET in plasma of KO rats decreased significantly, and the heart injury was more serious. Interestingly, we found that after CYP2J deletion, the heart initiated a self-protection mechanism by upregulating cardiac mechanism factors Myh7, Dsp, Tnni3, Tnni2, and Scn5a, as well as mitochondrial fusion factors Mfn2 and Opa1. However, this protective effect disappeared with aging. In conclusion, CYP2J deficiency not only reduces the amount of EETs, but also plays a dual regulatory role in cardiac function.
AB - Cytochrome P450 2J2 (CYP2J2) enzyme is widely expressed in aortic endothelial cells and cardiac myocytes and affects cardiac function, but the underlying mechanism is still unclear. Based on CYP2J knockout (KO) rats, we have directly studied the metabolic regulation of CYP2J on cardiac function during aging. The results showed that CYP2J deficiency significantly reduced the content of epoxyeicosatrienoic acids (EETs) in plasma, aggravated myocarditis, myocardial hypertrophy, as well as fibrosis, and inhibited the mitochondrial energy metabolism signal network Pgc-1α/Ampk/Sirt1. With the increase of age, the levels of 11,12-EET and 14,15-EET in plasma of KO rats decreased significantly, and the heart injury was more serious. Interestingly, we found that after CYP2J deletion, the heart initiated a self-protection mechanism by upregulating cardiac mechanism factors Myh7, Dsp, Tnni3, Tnni2, and Scn5a, as well as mitochondrial fusion factors Mfn2 and Opa1. However, this protective effect disappeared with aging. In conclusion, CYP2J deficiency not only reduces the amount of EETs, but also plays a dual regulatory role in cardiac function.
KW - CYP2J
KW - Cardiac function
KW - Cardiovascular disease
KW - Epoxyeicosatrienoic acids (EETs)
KW - Metabolic regulation
UR - https://www.scopus.com/pages/publications/85163778097
U2 - 10.1016/j.taap.2023.116610
DO - 10.1016/j.taap.2023.116610
M3 - 文章
C2 - 37385478
AN - SCOPUS:85163778097
SN - 0041-008X
VL - 473
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
M1 - 116610
ER -
