ALDH2 mediates the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on improving cardiac remodeling.

Animals Aldehyde Dehydrogenase, Mitochondrial / genetics Ventricular Remodeling / drug effects Sodium-Glucose Transporter 2 Inhibitors / pharmacology Myocytes, Cardiac / drug effects Mice, Knockout Disease Models, Animal Humans Mice, Inbred C57BL Male Signal Transduction Glucosides / pharmacology Cardiomegaly / enzymology Mice Hypertrophy, Left Ventricular / physiopathology Benzhydryl Compounds / pharmacology Ventricular Function, Left / drug effects Rats Databases, Genetic
Aldehyde dehydrogenase 2 Cardiac remodeling Methylation Sodium-glucose cotransporter-2 inhibitors Sodium/proton exchanger 1

Journal

Cardiovascular diabetology
ISSN: 1475-2840
Titre abrégé: Cardiovasc Diabetol
Pays: England
ID NLM: 101147637

Informations de publication

Date de publication:
26 Oct 2024
Historique:
received: 27 07 2024
accepted: 16 10 2024
medline: 27 10 2024
pubmed: 27 10 2024
entrez: 27 10 2024
Statut: epublish

Résumé

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are now recommended for patients with heart failure, but the mechanisms that underlie the protective role of SGLT2i in cardiac remodeling remain unclear. Aldehyde dehydrogenase 2 (ALDH2) effectively prevents cardiac remodeling. Here, the key role of ALDH2 in the efficacy of SGLT2i on cardiac remodeling was studied. Analysis of multiple transcriptomic datasets and two-sample Mendelian randomization were performed to find out the differentially expressed genes between pathological cardiac hypertrophy models (patients) and controls. A pathological cardiac hypertrophy mouse model was established via transverse aortic constriction (TAC) or isoproterenol (ISO). Cardiomyocyte-specific ALDH2 knockout mice (ALDH2 Only ALDH2 was differentially expressed when the differentially expressed genes obtained via Mendelian analysis and the differentially expressed genes obtained from the multiple transcriptome datasets were combined. Mendelian analysis revealed that ALDH2 was negatively related to the severity of myocardial hypertrophy in patients. DAPA alleviated cardiac remodeling in mouse hearts subjected to TAC or ISO. ALDH2 expression was reduced, whereas ALDH2 expression was restored by DAPA in hypertrophic hearts. Cardiomyocyte specific ALDH2 knockout abolished the protective role of DAPA in preventing cardiac remodeling. ALDH2 expression and activity were increased in DAPA-treated neonatal rat primary cardiomyocytes (NRCMs), H9C2 cells and AC16 cells. Moreover, DAPA upregulated ALDH2 in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes. Sodium/proton exchanger 1 (NHE1) inhibition contributed to the regulation of ALDH2 by DAPA. DAPA suppressed the production of reactive oxygen species (ROS), downregulated DNA methyltransferase 1 (DNMT1) and subsequently reduced the ALDH2 promoter methylation level. Further studies revealed that DAPA enhanced the binding of nuclear transcription factor Y, subunit A (NFYA) to the promoter region of ALDH2, which was due to the decreased promoter methylation level of ALDH2. The upregulation of ALDH2 plays a critical role in the protection of DAPA against cardiac remodeling. DAPA enhances the binding of NFYA to the ALDH2 promoter by reducing the ALDH2 promoter methylation level through NHE1/ROS/DNMT1 pathway.

Sections du résumé

BACKGROUND BACKGROUND
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are now recommended for patients with heart failure, but the mechanisms that underlie the protective role of SGLT2i in cardiac remodeling remain unclear. Aldehyde dehydrogenase 2 (ALDH2) effectively prevents cardiac remodeling. Here, the key role of ALDH2 in the efficacy of SGLT2i on cardiac remodeling was studied.
METHODS METHODS
Analysis of multiple transcriptomic datasets and two-sample Mendelian randomization were performed to find out the differentially expressed genes between pathological cardiac hypertrophy models (patients) and controls. A pathological cardiac hypertrophy mouse model was established via transverse aortic constriction (TAC) or isoproterenol (ISO). Cardiomyocyte-specific ALDH2 knockout mice (ALDH2
RESULTS RESULTS
Only ALDH2 was differentially expressed when the differentially expressed genes obtained via Mendelian analysis and the differentially expressed genes obtained from the multiple transcriptome datasets were combined. Mendelian analysis revealed that ALDH2 was negatively related to the severity of myocardial hypertrophy in patients. DAPA alleviated cardiac remodeling in mouse hearts subjected to TAC or ISO. ALDH2 expression was reduced, whereas ALDH2 expression was restored by DAPA in hypertrophic hearts. Cardiomyocyte specific ALDH2 knockout abolished the protective role of DAPA in preventing cardiac remodeling. ALDH2 expression and activity were increased in DAPA-treated neonatal rat primary cardiomyocytes (NRCMs), H9C2 cells and AC16 cells. Moreover, DAPA upregulated ALDH2 in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes. Sodium/proton exchanger 1 (NHE1) inhibition contributed to the regulation of ALDH2 by DAPA. DAPA suppressed the production of reactive oxygen species (ROS), downregulated DNA methyltransferase 1 (DNMT1) and subsequently reduced the ALDH2 promoter methylation level. Further studies revealed that DAPA enhanced the binding of nuclear transcription factor Y, subunit A (NFYA) to the promoter region of ALDH2, which was due to the decreased promoter methylation level of ALDH2.
CONCLUSIONS CONCLUSIONS
The upregulation of ALDH2 plays a critical role in the protection of DAPA against cardiac remodeling. DAPA enhances the binding of NFYA to the ALDH2 promoter by reducing the ALDH2 promoter methylation level through NHE1/ROS/DNMT1 pathway.

Identifiants

DOI: 10.1186/s12933-024-02477-8 PMID: 39462342
pubmed: 39462342
doi: 10.1186/s12933-024-02477-8
pii: 10.1186/s12933-024-02477-8
doi:

Substances chimiques

Aldehyde Dehydrogenase, Mitochondrial EC 1.2.1.3
Sodium-Glucose Transporter 2 Inhibitors 0
ALDH2 protein, mouse EC 1.2.1.3
ALDH2 protein, human EC 1.2.1.3
Glucosides 0
Aldh2 protein, rat EC 1.2.1.3
Benzhydryl Compounds 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

380

Subventions

Organisme : National Natural Science Foundation of China
ID : 82072141, 82272240, 82202376
Organisme : National Natural Science Foundation of China
ID : 82072141, 82272240, 82202376
Organisme : National Natural Science Foundation of China
ID : 82072141, 82272240, 82202376
Organisme : Natural Science Foundation of Shandong Province
ID : ZR2022QH225
Organisme : Clinical Research Foundation of Shandong University
ID : 2020SDUCRCC014
Organisme : State Key Program of the National Natural Science Foundation of China
ID : 82030059

Informations de copyright

© 2024. The Author(s).

Références

Tani H, Sadahiro T, Yamada Y, Isomi M, Yamakawa H, Fujita R, Abe Y, Akiyama T, Nakano K, Kuze Y, et al. Direct reprogramming improves cardiac function and reverses fibrosis in chronic myocardial infarction. Circulation. 2023;147(3):223–38.
doi: 10.1161/CIRCULATIONAHA.121.058655 pubmed: 36503256
Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, et al. 2022 AHA/ACC/HFSA Guideline for the management of heart failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895–1032.
pubmed: 35363499
Chai R, Xue W, Shi S, Zhou Y, Du Y, Li Y, Song Q, Wu H, Hu Y. Cardiac remodeling in heart failure: role of pyroptosis and its therapeutic implications. Front Cardiovasc Med. 2022;9:870924.
doi: 10.3389/fcvm.2022.870924 pubmed: 35509275 pmcid: 9058112
Gonzalez A, Ravassa S, Beaumont J, Lopez B, Diez J. New targets to treat the structural remodeling of the myocardium. J Am Coll Cardiol. 2011;58(18):1833–43.
doi: 10.1016/j.jacc.2011.06.058 pubmed: 22018293
Xing J. Venoarterial extracorporeal membrane oxygenation in acute myocardial infarction. Emerg Crit Care Med. 2024;4(1):1–3.
McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599–726.
doi: 10.1093/eurheartj/ehab368 pubmed: 34447992
Vallon V. The mechanisms and therapeutic potential of SGLT2 inhibitors in diabetes mellitus. Annu Rev Med. 2015;66:255–70.
doi: 10.1146/annurev-med-051013-110046 pubmed: 25341005
Girerd N, Zannad F. SGLT2 inhibition in heart failure with reduced or preserved ejection fraction: finding the right patients to treat. J Intern Med. 2023;293(5):550–8.
doi: 10.1111/joim.13620 pubmed: 36871279
Li X, Lu Q, Qiu Y, do Carmo JM, Wang Z, da Silva AA, Mouton A, Omoto ACM, Hall ME, Li J, et al. Direct cardiac actions of the sodium glucose co‐transporter 2 inhibitor empagliflozin improve myocardial oxidative phosphorylation and attenuate pressure‐overload heart failure. J Am Heart Assoc. 2021;10(6).
Ni L, Yuan C, Chen G, Zhang C, Wu X: SGLT2i: beyond the glucose-lowering effect. Cardiovasc Diabetol. 2020;19(1).
Santos-Gallego CG, Requena-Ibanez JA, San Antonio R, Ishikawa K, Watanabe S, Picatoste B, Flores E, Garcia-Ropero A, Sanz J, Hajjar RJ, et al. Empagliflozin ameliorates adverse left ventricular remodeling in nondiabetic heart failure by enhancing myocardial energetics. J Am Coll Cardiol. 2019;73(15):1931–44.
doi: 10.1016/j.jacc.2019.01.056 pubmed: 30999996
Maeder MT, Khammy O, dos Remedios C, Kaye DM. Myocardial and systemic iron depletion in heart failure. J Am Coll Cardiol. 2011;58(5):474–80.
doi: 10.1016/j.jacc.2011.01.059 pubmed: 21777743
Angermann CE, Santos-Gallego CG, Requena-Ibanez JA, Sehner S, Zeller T, Gerhardt LMS, Maack C, Sanz J, Frantz S, Fuster V, et al. Empagliflozin effects on iron metabolism as a possible mechanism for improved clinical outcomes in non-diabetic patients with systolic heart failure. Nat Cardiovasc Res. 2023;2(11):1032–43.
doi: 10.1038/s44161-023-00352-5 pubmed: 39196095 pmcid: 11358002
Chen Y, Peng D. New insights into the molecular mechanisms of SGLT2 inhibitors on ventricular remodeling. Int Immunopharmacol. 2023;118: 110072.
doi: 10.1016/j.intimp.2023.110072 pubmed: 37018976
Zhao Y, Wang B, Zhang J, He D, Zhang Q, Pan C, Yuan Q, Shi Y, Tang H, Xu F, et al. ALDH2 (Aldehyde Dehydrogenase 2) protects against hypoxia-induced pulmonary hypertension. Arterioscler Thromb Vasc Biol. 2019;39(11):2303–19.
doi: 10.1161/ATVBAHA.119.312946 pubmed: 31510791
Zhang J, Guo Y, Zhao X, Pang J, Pan C, Wang J, Wei S, Yu X, Zhang C, Chen Y, et al. The role of aldehyde dehydrogenase 2 in cardiovascular disease. Nat Rev Cardiol. 2023;20(7):495–509.
doi: 10.1038/s41569-023-00839-5 pubmed: 36781974
Li W, Yin L, Sun X, Wu J, Dong Z, Hu K, Sun A, Ge J. Alpha-lipoic acid protects against pressure overload-induced heart failure via ALDH2-dependent Nrf1-FUNDC1 signaling. Cell Death Dis. 2020;11(7):599.
doi: 10.1038/s41419-020-02805-2 pubmed: 32732978 pmcid: 7393127
Guo H, Yu X, Liu Y, Paik DT, Justesen JM, Chandy M, Jahng JWS, Zhang T, Wu W, Rwere F et al: SGLT2 inhibitor ameliorates endothelial dysfunction associated with the common ALDH2 alcohol flushing variant. Sci Transl Med. 2023;15(680):eabp9952.
Rui H, Yu H, Zou D, Chi K, Xu P, Song X, Liu L, Wu X, Wang J, Xue L. Vaspin alleviates pathological cardiac hypertrophy by regulating autophagy-dependent myocardial senescence. Emerg Crit Care Med. 2024;4(1):4–15.
doi: 10.1097/EC9.0000000000000097
Lin K, Yang N, Luo W, Qian J-f, Zhu W-w, Ye S-j, Yuan C-x, Xu D-y, Liang G, Huang W-j, et al. Direct cardio-protection of Dapagliflozin against obesity-related cardiomyopathy via NHE1/MAPK signaling. Acta Pharmacol Sin. 2022;43(10):2624–35.
Li X, Wang M, Kalina JO, Preckel B, Hollmann MW, Albrecht M, Zuurbier CJ, Weber NC. Empagliflozin prevents oxidative stress in human coronary artery endothelial cells via the NHE/PKC/NOX axis. Redox Biol. 2024;69: 102979.
doi: 10.1016/j.redox.2023.102979 pubmed: 38061206
Costantino S, Paneni F, Mitchell K, Mohammed SA, Hussain S, Gkolfos C, Berrino L, Volpe M, Schwarzwald C, Luscher TF, et al. Hyperglycaemia-induced epigenetic changes drive persistent cardiac dysfunction via the adaptor p66(Shc). Int J Cardiol. 2018;268:179–86.
doi: 10.1016/j.ijcard.2018.04.082 pubmed: 30047409
Braunwald E. The war against heart failure: the Lancet lecture. The Lancet. 2015;385(9970):812–24.
doi: 10.1016/S0140-6736(14)61889-4
Catalucci D, Latronico MVG, Ellingsen O, Condorelli G. Physiological myocardial hypertrophy: How and why? FBL. 2008;13(1):312–24.
Mudd JO, Kass DA. Tackling heart failure in the twenty-first century. Nature. 2008;451(7181):919–28.
doi: 10.1038/nature06798 pubmed: 18288181
Solomon SD, McMurray JJV, Claggett B, de Boer RA, DeMets D, Hernandez AF, Inzucchi SE, Kosiborod MN, Lam CSP, Martinez F, et al. Dapagliflozin in Heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089–98.
doi: 10.1056/NEJMoa2206286 pubmed: 36027570
Han S, Hagan DL, Taylor JR, Xin L, Meng W, Biller SA, Wetterau JR, Washburn WN, Whaley JM. Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats. Diabetes. 2008;57(6):1723–9.
doi: 10.2337/db07-1472 pubmed: 18356408
Vallon V, Verma S. Effects of SGLT2 inhibitors on kidney and cardiovascular function. Annu Rev Physiol. 2021;83(1):503–28.
doi: 10.1146/annurev-physiol-031620-095920 pubmed: 33197224
Chen S, Wang Q, Christodoulou A, Mylonas N, Bakker D, Nederlof R, Hollmann MW, Weber NC, Coronel R, Wakker V, et al. Sodium glucose cotransporter-2 inhibitor empagliflozin reduces infarct size independently of sodium glucose cotransporter-2. Circulation. 2023;147(3):276–9.
doi: 10.1161/CIRCULATIONAHA.122.061688 pubmed: 36649392
van der Aart-van der Beek AB, de Boer RA, Heerspink HJL. Kidney and heart failure outcomes associated with SGLT2 inhibitor use. Nat Rev Nephrol. 2022;18(5):294–306.
Gao M, Bhatia K, Kapoor A, Badimon J, Pinney SP, Mancini DM, Santos-Gallego CG, Lala A: SGLT2 inhibitors, functional capacity, and quality of life in patients with heart failure. JAMA Network Open. 2024;7(4).
Yang J, Li L, Zheng X, Lu Z, Zhou H. Dapagliflozin attenuates myocardial hypertrophy via activating the SIRT1/HIF-1α signaling pathway. Biomed Pharmacother. 2023;165: 115125.
doi: 10.1016/j.biopha.2023.115125 pubmed: 37421782
Arow M, Waldman M, Yadin D, Nudelman V, Shainberg A, Abraham NG, Freimark D, Kornowski R, Aravot D, Hochhauser E, et al. Sodium-glucose cotransporter 2 inhibitor Dapagliflozin attenuates diabetic cardiomyopathy. Cardiovasc Diabetol. 2020;19(1):7.
doi: 10.1186/s12933-019-0980-4 pubmed: 31924211 pmcid: 6953156
Yang K, Cui S, Wang J, Xu T, Du H, Yue H, Ye H, Guo J, Zhang J, Li P, et al. Early Progression of abdominal aortic aneurysm is decelerated by improved endothelial barrier function via ALDH2‐LIN28B‐ELK3 signaling. Adv Sci. 2023;10(32).
Zhong S, Li L, Zhang YL, Zhang L, Lu J, Guo S, Liang N, Ge J, Zhu M, Tao Y, et al. Acetaldehyde dehydrogenase 2 interactions with LDLR and AMPK regulate foam cell formation. J Clin Invest. 2019;129(1):252–67.
doi: 10.1172/JCI122064 pubmed: 30375985
Li W, Yin L, Sun X, Wu J, Dong Z, Hu K, Sun A, Ge J. Alpha-lipoic acid protects against pressure overload-induced heart failure via ALDH2-dependent Nrf1-FUNDC1 signaling. Cell Death Dis. 2020;11(7).
Zhang Y, Zou R, Abudureyimu M, Liu Q, Ma J, Xu H, Yu W, Yang J, Jia J, Qian S et al: Mitochondrial aldehyde dehydrogenase rescues against diabetic cardiomyopathy through GSK3β-mediated preservation of mitochondrial integrity and Parkin-mediated mitophagy. J Mol Cell Biol. 2023;15(9).
Palmiero G, Cesaro A, Vetrano E, Pafundi PC, Galiero R, Caturano A, Moscarella E, Gragnano F, Salvatore T, Rinaldi L, et al. Impact of SGLT2 inhibitors on heart failure: from pathophysiology to clinical effects. Int J Mol Sci. 2021;22(11).
Uthman L, Baartscheer A, Schumacher CA, Fiolet JWT, Kuschma MC, Hollmann MW, Coronel R, Weber NC, Zuurbier CJ. Direct cardiac actions of sodium glucose cotransporter 2 inhibitors target pathogenic mechanisms underlying heart failure in diabetic patients. Front Physiol. 2018;9:1575.
doi: 10.3389/fphys.2018.01575 pubmed: 30519189 pmcid: 6259641
Berger JH, Matsuura TR, Bowman CE, Taing R, Patel J, Lai L, Leone TC, Reagan JD, Haldar SM, Arany Z, et al. SGLT2 inhibitors act independently of SGLT2 to confer benefit for HFrEF in mice. Circ Res. 2024.
Xia H, Zahra A, Jia M, Wang Q, Wang Y, Campbell SL, Wu J. Na(+)/H(+) Exchanger 1, a potential therapeutic drug target for cardiac hypertrophy and heart failure. Pharmaceuticals. 2022;15(7).
Yeves AM, Ennis IL. Na(+)/H(+) exchanger and cardiac hypertrophy. Hipertens Riesgo Vasc. 2020;37(1):22–32.
doi: 10.1016/j.hipert.2019.09.002 pubmed: 31601481
Chen S, Overberg K, Ghouse Z, Hollmann MW, Weber NC, Coronel R, Zuurbier CJ. Empagliflozin mitigates cardiac hypertrophy through cardiac RSK/NHE-1 inhibition. Biomed Pharmacother. 2024;174: 116477.
doi: 10.1016/j.biopha.2024.116477 pubmed: 38522235
Chen S, Wang Q, Bakker D, Hu X, Zhang L, van der Made I, Tebbens AM, Kovacshazi C, Giricz Z, Brenner GB, et al: Empagliflozin prevents heart failure through inhibition of the NHE1-NO pathway, independent of SGLT2. Basic Res Cardiol. 2024.
Chang W-T, Shih J-Y, Lin Y-W, Chen Z-C, Kan W-C, Lin T-H, Hong C-S. Dapagliflozin protects against doxorubicin-induced cardiotoxicity by restoring STAT3. Arch Toxicol. 2022;96(7):2021–32.
doi: 10.1007/s00204-022-03298-y pubmed: 35438302
Santos-Gallego CG, Requena-Ibáñez JA, Picatoste B, Fardman B, Ishikawa K, Mazurek R, Pieper M, Sartori S, Rodriguez-Capitán J, Fuster V, et al. Cardioprotective effect of empagliflozin and circulating ketone bodies during acute myocardial infarction. Circ Cardiovasc Imaging. 2023;16(4).
Zhao Y, Fan X, Wang Q, Zhen J, Li X, Zhou P, Lang Y, Sheng Q, Zhang T, Huang T, et al. ROS promote hyper-methylation of NDRG2 promoters in a DNMTS-dependent manner: contributes to the progression of renal fibrosis. Redox Biol. 2023;62: 102674.
doi: 10.1016/j.redox.2023.102674 pubmed: 36989575 pmcid: 10074964
Campos AC, Molognoni F, Melo FH, Galdieri LC, Carneiro CR, D’Almeida V, Correa M, Jasiulionis MG. Oxidative stress modulates DNA methylation during melanocyte anchorage blockade associated with malignant transformation. Neoplasia. 2007;9(12):1111–21.
doi: 10.1593/neo.07712 pubmed: 18084618 pmcid: 2134907
Yang M, Wang A, Li C, Sun J, Yi G, Cheng H, Liu X, Wang Z, Zhou Y, Yao G, et al. Methylation-induced silencing of ALDH2 facilitates lung adenocarcinoma bone metastasis by activating the MAPK pathway. Front Oncol. 2020;10.
Tran T-O, Vo TH, Lam LHT, Le NQK. ALDH2 as a potential stem cell-related biomarker in lung adenocarcinoma: Comprehensive multi-omics analysis. Comput Struct Biotechnol J. 2023;21:1921–9.
doi: 10.1016/j.csbj.2023.02.045 pubmed: 36936815 pmcid: 10018390
Costantino S, Camici GG, Mohammed SA, Volpe M, Lüscher TF, Paneni F. Epigenetics and cardiovascular regenerative medicine in the elderly. Int J Cardiol. 2018;250:207–14.
doi: 10.1016/j.ijcard.2017.09.188 pubmed: 28988828

Auteurs

Han Liu (H)

Department of Emergency and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.

Bingchen Jiang (B)

Department of Emergency and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.

Rui Hua (R)

Department of Emergency and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.

Xuehao Liu (X)

Department of Emergency and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.

Bao Qiao (B)

Department of Emergency and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.

Xiangxin Zhang (X)

Department of Emergency and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.

Xilong Liu (X)

Department of Emergency and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.

Wenjun Wang (W)

Department of Intensive Care Unit, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People's Republic of China.

Qiuhuan Yuan (Q)

Department of Emergency and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.

Bailu Wang (B)

NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Clinical Trial Center, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.

Shujian Wei (S)

Department of Emergency and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. weishujian@sdu.edu.cn.
Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. weishujian@sdu.edu.cn.
Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. weishujian@sdu.edu.cn.
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. weishujian@sdu.edu.cn.

Yuguo Chen (Y)

Department of Emergency and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. chen919085@sdu.edu.cn.
Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. chen919085@sdu.edu.cn.
Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. chen919085@sdu.edu.cn.
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China. chen919085@sdu.edu.cn.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines mitochondriales › Aldehyde dehydrogenase, mitochondrial › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Fonction ventriculaire › Remodelage ventriculaire › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hypoglycémiants › Inhibiteurs du cotransporteur sodium-glucose de type 2 › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › Cellules › Cellules musculaires › Myocytes cardiaques › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › Glucides › Hétérosides › Glucosides › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › États, signes et symptômes pathologiques › États anatomopathologiques › Hypertrophie › Cardiomégalie › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › États, signes et symptômes pathologiques › États anatomopathologiques › Hypertrophie › Cardiomégalie › Hypertrophie ventriculaire gauche › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Composés benzhydryliques › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Fonction ventriculaire › Fonction ventriculaire gauche › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › ALDH2 mediates the effects of sodium-glucose...
questionsmedicales.fr › Sciences de l'information › Mémorisation et recherche des informations › Bases de données comme sujet › Bases de données factuelles › Bases de données génétiques › ALDH2 mediates the effects of sodium-glucose...