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Updated: May 21, 2025
Acute Myocardial Infarction in Rats
Published on: February 16, 2011
Cardiomyocyte specific CD38 deletion protects heart from acute myocardial infarction by activating Sirt3 signaling
Ke Wen1,2, Ya-Ting Zhang1,2, Qi-Hang Zhao1
1National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, 999 Xuefu Road, Honggutan District, Nanchang, 330031, Jiangxi, China.
Insights
Cardiomyocyte-specific CD38 deficiency improves heart function after acute myocardial infarction (AMI). This protection involves reduced fibrosis and apoptosis, mediated by the NAD+/Sirt3 pathway.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Metabolic Enzyme Research
Background:
- Acute myocardial infarction (AMI) presents a significant global health challenge.
- CD38, a metabolic enzyme, is implicated in various diseases, with prior studies showing its role in cardiac hypertrophy and ischemia-reperfusion injury.
- The specific function of CD38 within cardiomyocytes during AMI remains unelucidated.
Purpose of the Study:
- To investigate the role of cardiomyocyte-specific CD38 deficiency in the context of acute myocardial infarction.
- To elucidate the underlying molecular mechanisms by which CD38 influences cardiac function and cell survival during AMI.
Main Methods:
- Generation of cardiomyocyte-specific CD38-deficient mice (CD38CKO).
- Assessment of cardiac function and histological analysis in an AMI model.
- Evaluation of cardiomyocyte apoptosis, mitochondrial protein expression (Bcl2/Bax ratio, Mfn1, Mfn2), and signaling pathways (NAD+/Sirt3) in vivo and in vitro.
- Pharmacological inhibition of Sirt3 using 3-TYP.
Main Results:
- Cardiomyocyte-specific CD38 deficiency (CD38CKO) significantly improved cardiac function in AMI.
- CD38CKO reduced fibrosis in the peri-infarct zone and inhibited cardiomyocyte apoptosis.
- Protection against apoptosis was linked to an increased Bcl2/Bax ratio, elevated Mfn1/Mfn2 expression, and activation of the NAD+/Sirt3 pathway.
- Knockdown of CD38 protected cardiomyocytes from hypoxia-induced apoptosis, an effect reversed by Sirt3 inhibition.
Conclusions:
- Cardiomyocyte-specific CD38 deficiency confers protection against acute myocardial infarction.
- The protective effects are mediated by the suppression of cardiomyocyte apoptosis through the activation of NAD+/Sirt3 signaling pathways.
- Targeting CD38 in cardiomyocytes represents a potential therapeutic strategy for managing AMI.
Abstract:
Acute myocardial infarction (AMI) is serious disease with high morbidity and mortality worldwide. CD38 is an important metabolic enzyme and plays an important role in a variety of diseases. Our previous studies demonstrated that CD38 deficiency significantly reduced Ang-II-induced ventricular hypertrophy and cardiac ischemia-reperfusion injury. However, the roles of cardiomyocytic CD38 in acute myocardial infarction (AMI) remain unknown. Here, we reported that cardiomyocyte-specific CD38 deficiency (CD38CKO) significantly improved heart functions in AMI. We observed that CD38CKO remarkably reduced the fibrosis at the peri-infarct area, and inhibited the apoptosis of cardiomyocytes in infarcted area by elevating the ratio of mitochondrial Bcl2/Bax expression and increased the expressions of the mitochondrial fusion proteins Mfn1 and Mfn2 in the early stage of AMI. Consistently, knockdown of CD38 protected hypoxia-induced apoptosis in cardiomyocytes by increasing the ratio of Bcl2/Bax expression and decreasing cleaved caspase-3. More importantly, 3-TYP, a Sirt3 inhibitor, significantly increased hypoxia-induced apoptosis in CD38-deficient primary cardiomyocytes. In conclusion, our results demonstrated that CD38CKO suppressed apoptosis of cardiomyocytes in the infracted area of heart via activating NAD+/Sirt3-mediated signaling pathways.
