ALDOA protects cardiomyocytes against H/R-induced apoptosis and oxidative stress by regulating the VEGF/Notch 1/Jagged 1
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ALDOA protects cardiomyocytes against H/R‑induced apoptosis and oxidative stress by regulating the VEGF/Notch 1/Jagged 1 pathway Gaiying Luo1 · Rui Wang2 · Hui Zhou2 · Xiaoling Liu1 Received: 20 April 2020 / Accepted: 10 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Myocardial infarction (MI) is a myocardial necrosis disease caused by continuous ischemia and hypoxia. Abnormal expression of aldolase A (ALDOA) has been reported in cardiac hypertrophy, heart failure and other cardio-cerebrovascular diseases. The present study aims to explore the effects of ALDOA on hypoxia/reperfusion (H/R)-induced oxidative stress, and investigate the underlying mechanisms. ALDOA was expressed at a low level in blood samples from MI patients and H/R-induced H9C2 cardiomyocytes. Overexpression of ALDOA suppressed H/R-induced oxidative stress and apoptosis. Using co-immunoprecipitation and protein blots, we demonstrated that ALDOA modulates the Notch 1–Jagged 1 signalling pathway by upregulating VEGF. Taken together, our data reveal that ALDOA protects cardiomyocytes from H/R-induced oxidative stress through the VEGF/Notch 1/Jagged 1 axis, and should be investigated as a therapeutic target for the treatment of MI in future. Keywords Apoptosis · Aldolase A · Cardiomyocytes · Oxidative stress
Introduction Myocardial infarction (MI) is a cardiovascular disease of myocardial necrosis caused by continuous ischemia and hypoxia [1]. Oxidative stress is implicated in the pathogenesis of MI [2]. MI dramatically influences the cardiovascular, respiratory and digestive systems of patients, and even leads to devastating injury [3]. To date, the common therapeutic strategies for MI include intensive care, drug therapy, antiarrhythmic activity and reperfusion therapy [4]. Despite dramatic improvements in MI treatment, the incidence and prevalence of MI continue to increase [5]. Therefore, it is of value to illuminate the potential effects of pathogenesis-related genes on MI and investigate the underlying mechanisms.
* Xiaoling Liu [email protected] 1
Department of Clinical Laboratory, Xi’an No 5 Hospital, No. 112 West Main Street, Lianhu District, Xi’an 710082, Shaanxi, China
The Five Ward of Internal Medicine, Xi’an No 5 Hospital, Xi’an 710082, Shaanxi, China
2
Aldolase A (ALDOA) plays pivotal roles in energy balance, gluconeogenesis and glycolysis [6]. Abnormal expression of ALDOA results in cardiac hypertrophy, heart failure and other cardio-cerebrovascular diseases [7]. Previous studies revealed that ALDOA is dramatically upregulated in hypertrophic hearts [8, 9], and silencing of ALDOA inhibits cardiac hypertrophy in vivo [8]. Furthermore, ALDOA contributes to the myocardial stress-gene response [10]. Overexpression of ALDOA strengthens resistance to myocardial injury in rats [6]. A recent study revealed that ALDOA is differentially expressed in patients during MI compared to control [11]. However, the role of ALDOA in MI and the underlying mechanisms are poorly understand. Vascular
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