The Effect of HIF1-α/NF-κB/MMP2 Signaling Pathways Mediated by ALDH2 on Chronic Intermittent Hypoxia Induced Myocardial Injury in Rats
DOI:
https://doi.org/10.54097/wxcz8y41Keywords:
Myocardial Injury, Chronic Intermittent Hypoxia, ALDH2, HIF1-α, NF-κB, MMP2Abstract
(1) Objective: To investigate the effect of HIF1-α/NF-κB/MMP2 signaling pathways mediated by ALDH2 on chronic intermittent hypoxia induced myocardial injury in rats. (2) Methods: Thirty SD rats were randomly assigned to three groups (10 rats in each group): control group (CONTROL), chronic intermittent hypoxia group (CIH), and CIH + ALDH2 group. Rats in the CIH + ALDH2 group were established by an intraperitoneal injection of the ALDH2 activator, Alda-1 (20 mg/kg), once a day for three consecutive days. After three months, changes in ventricular function were determined by ultrasound. The expressions of HIF1-α, NF-κB, and MMP2 proteins were detected by protein blotting, and the concentration of 4-HNE in myocardial tissue was measured. (3) Results: Compared with the control group, echocardiography showed that rats in the CIH group had significantly reduced myocardial function, elevated protein levels of HIF1-α, NF-κB, and MMP2 in myocardial tissues, and increased the expression of 4-HNE in myocardial tissues (P<0.01); Compared with the CIH group, rats in the CIH + ALDH2 group showed significant improvement in myocardial function, decreased protein levels of HIF1-α, NF-κB, and MMP2 in myocardial tissue, and decreased the expression of 4-HNE in myocardial tissue (P<0.01). (4) Conclusion: Chronic intermittent hypoxia increases the expression of HIF1-α to damage the myocardium and affect cardiac function, and ALDH2 inhibits the expression of HIF1-α to protect the myocardium.
Downloads
References
Yeghiazarians Y, Jneid H, Tietjens J R, et al. Obstructive Sleep Apnea and Cardiovascular Disease: A Scientific Statement From the American Heart Association [J]. Circulation, 2021, 144 (3):56-67.
Pereyra K, Las H A, Toledo C, et al. Chemogenetic inhibition of NTS astrocytes normalizes cardiac autonomic control and ameliorate hypertension during chronic intermittent hypoxia [J]. Biol Res, 2023,56(1):57.
Gabryelska A, Sochal M, Turkiewicz S, et al. Relationship between HIF-1 and Circadian Clock Proteins in Obstructive Sleep Apnea Patients-Preliminary Study [J]. J Clin Med, 2020, 9 (5).
Yang Y, Zou P, He L, et al. CBL aggravates Ang II-induced cardiac hypertrophy via the VHL/HIF-1alpha pathway [J]. Exp Cell Res, 2021,405(2):112730.
Xu X, Zhen P H, Yu F C, et al. Chronic intermittent hypoxia accelerates cardiac dysfunction and cardiac remodeling during cardiac pressure overload in mice and can be alleviated by PHD3 over expression[J]. Front Cardiovasc Med, 2022,9: 974345.
D'Ignazio L, Shakir D, Batie M, et al. HIF-1beta Positively Regulates NF-kappaB Activity via Direct Control of TRAF6 [J]. Int J Mol Sci, 2020,21(8).
Wang J, Deng M, Yang J, et al. FOXN4 affects myocardial ischemia-reperfusion injury through HIF-1alpha/ MMP2-mediated ferroptosis of cardiomyocytes[J]. Cell Mol Biol (Noisy-le-grand), 2023,69(6):214-225.
Gao R, Lv C, Qu Y, et al. Remote Ischemic Conditioning Mediates Cardio-protection After Myocardial Ischemia/ Reperfusion Injury by Reducing 4-HNE Levels and Regulating Autophagy via the ALDH2/SIRT3/HIF1alpha Signaling Pathway [J]. J Cardiovasc Transl Res, 2023.
Gao Q, Wang H J, Wang X M, et al. Activation of ALDH2 with ethanol attenuates diabetes induced myocardial injury in rats[J]. Food Chem Toxicol, 2013,56:419-424.
Tan X, Chen Y F, Zou S Y, et al. ALDH2 attenuates ischemia and reperfusion injury through regulation of mitochondrial fusion and fission by PI3K/AKT/mTOR pathway in diabetic cardiomyopathy[J]. Free Radic Biol Med, 2023,195:219-230.
Tan K C, Chow W S, Lam J C, et al. HDL dysfunction in obstructive sleep apnea[J]. Atherosclerosis, 2006, 184(2):377-382.
Shi J, Piao J, Liu B, et al. Obstructive sleep apnea increases systolic and diastolic blood pressure variability in hypertensive patients[J]. Blood Press Monit, 2017,22(4):208-212.
Holscher M, Schafer K, Krull S, et al. Unfavourable consequences of chronic cardiac HIF-1alpha stabilization[J]. Cardiovasc Res, 2012,94(1):77-86.
Sano M, Minamino T, Toko H, et al. p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload[J]. Nature, 2007,446(7134):444-448.
Wei Q, Bian Y, Yu F, et al. Chronic intermittent hypoxia induces cardiac inflammation and dysfunction in a rat obstructive sleep apnea model [J]. J Biomed Res, 2016,30 (6): 490-495.
Yu L M, Zhang W H, Han X X, et al. Hypoxia-Induced ROS Contribute to Myoblast Pyroptosis during Obstructive Sleep Apnea via the NF-kappaB/HIF-1alpha Signaling Pathway [J]. Oxid Med Cell Longev, 2019:4596368.
Wang D, Liu X, Li M, et al. HIF-1alpha regulates the cell viability in radioiodine-resistant papillary thyroid carcinoma cells induced by hypoxia through PKM2/NF-kappaB signaling pathway [J]. Mol Carcinog, 2023.
Huang B, Ding J, Guo H, et al. SIRT3 Regulates the ROS-FPR1/HIF-1alpha Axis under Hypoxic Conditions to Influence Lung Cancer Progression[J]. Cell Biochem Biophys, 2023,81 (4): 813-821.
Ma H, Lou K, Shu Q, et al. Aldehyde dehydrogenase 2 deficiency reinforces formaldehyde-potentiated pro-inflammatory responses and glycolysis in macrophages [J]. J Biochem Mol Toxicol, 2023: e23518.
Hong-Ju W ,Pin-Fang K ,Hong-Wei Y , et al.[Anti-apoptotic role of mitochondrial aldehyde dehydrogenase 2 in myocardial ischemia/reperfusion injury in diabetic rats].[J].Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 2012, 32(3):345-8.
Chang Y C, Lee H L, Yang W, et al. A common East-Asian ALDH2 mutation causes metabolic disorders and the therapeutic effect of ALDH2 activators[J]. Nat Commun, 2023, 14 (1):5971.
Hua Y, Chen H, Zhao X, et al. Alda‑1, an aldehyde dehydrogenase‑2 agonist, improves long‑term survival in rats with chronic heart failure following myocardial infarction[J]. Mol Med Rep, 2018,18(3):3159-3166.
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
