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Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission
Open accessAbstract
Impaired cardiac microvascular function contributes to diabetic cardiovascular complications although effective therapy remains elusive. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor recently approved for treatment of type 2 diabetes, promotes glycosuria excretion and offers cardioprotective actions beyond its glucose-lowering effects. This study was designed to evaluate the effect of empagliflozin on cardiac microvascular injury in diabetes and the underlying mechanism involved with a focus on mitochondria. Our data revealed that empagliflozin improved diabetic myocardial structure and function, preserved cardiac microvascular barrier function and integrity, sustained eNOS phosphorylation and endothelium-dependent relaxation, as well as improved microvessel density and perfusion. Further study suggested that empagliflozin exerted its effects through inhibition of mitochondrial fission in an adenosine monophosphate (AMP)-activated protein kinase (AMPK)-dependent manner. Empagliflozin restored AMP-to-ATP ratio to trigger AMPK activation, suppressed Drp1 S616 phosphorylation, and increased Drp1 S637 phosphorylation, ultimately leading to inhibition of mitochondrial fission. The empagliflozin-induced inhibition of mitochondrial fission preserved cardiac microvascular endothelial cell (CMEC) barrier function through suppressed mitochondrial reactive oxygen species (mtROS) production and subsequently oxidative stress to impede CMEC senescence. Empagliflozin-induced fission loss also favored angiogenesis by promoting CMEC migration through amelioration of F-actin depolymerization. Taken together, these results indicated the therapeutic promises of empagliflozin in the treatment of pathological microvascular changes in diabetes.
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“Empagliflozin exerted its protective roles via inhibition of AMPK-dependent mitochondrial fission [229].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [229]
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“Empagliflozin recovered the AMP-to-ATP ratio that is necessary for triggering AMPK activation [229].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [229]
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“In the meantime, DRP1-S616 phosphorylation was decreased, while DRP1-S637 phosphorylation was increased, ultimately leading to mitochondrial fission [229].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [229]
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1 retracted
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AMP-activated protein kinase mediates mitochondrial fission in response to energy stress
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Feng, J., Li, H., Zhang, Y., Wang, Q., Zhao, S., Meng, P., & Li, J. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000495896 · Cited by 37
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“The phosphorylation of Drp1 at different amino acid residues plays opposite roles in mitochondrial fission: phosphorylation at Ser(616) and Ser(637) is responsible for the initiation and inhibition of fission, respectively (10, 13).”
BackgroundSodium glucose cotransporter 2 inhibitors: mechanisms of action in heart failure
Dutka, M., Bobiński, R., Ulman-Włodarz, I., Hajduga, M. B., Bujok, J., Pająk, C., & Ćwiertnia, M. (2020) · Heart Failure Reviews · doi:10.1007/s10741-020-10041-1 · Cited by 40
“Activation of AMPK modulates Drp1 phosphorylation in such a way that mitochondrial fission is inhibited in cardiomyocytes [79].”
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“…to reduce free radical-producing NAPDH oxidase in the kidney [170,171] and endothelial cells [170,172] by inhibiting mitochondrial ROS production [173] and activating AMPK-dependent mitophagy in endothelial cells [174], and by reducing the production of pro-inflammatory…”
Wang, H., Zhao, X., Ni, C., Dai, Y., & Guo, Y. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.8823 · Cited by 35
“Notably, these actin proteins also facilitate the recruitment of dynamin-related protein 1 (Drp1) to the mitochondria and subsequent mitochondrial fission (14,15).”
RetractedZhu, D., Zhang, X., Wang, F., Ye, Q., Yang, C., & Liu, D. (2021) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2021.109170 · Cited by 36
Benefits of SGLT2 inhibitors in arrhythmias
Gao, J., Xue, G., Zhan, G., Wang, X., Li, J., Yang, X., & Xia, Y. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.1011429 · Cited by 40
“As one of the causes of cardiovascular disease, eNOS can be observed in cardiomyocytes, where empagliflozin treatment triggers eNOS phosphorylation, confirming its cardioprotective abilities (104).”
BackgroundRole of formin INF2 in human diseases
Zhao, Y., Zhang, H., Wang, H., Ye, M., & Jin, X. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06869-x · Cited by 32
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Li, T., Fang, T., Xu, L., Liu, X., Li, X., Xue, M., Yu, X., Sun, B., & Chen, L. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.622153 · Cited by 34
“In diabetic mice, empagliflozin treatment activated AMPK, which led to inhibition of mitochondrial fissions and alleviation of cardiac microvascular injury (Zhou et al., 2018).”
BackgroundCai, C., Wu, F., Zhuang, B., Ou, Q., Peng, X., Shi, N., Peng, L., Li, Z., Wang, J., Cai, S., et al. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101553 · Cited by 34
“In fact, previous studies have identified mitophagy as a potential target of empagliflozin [55,56].”
BackgroundSodium-glucose cotransporter 2 inhibitors and mitochondrial functions: state of the art
Yaribeygi, H., Maleki, M., Butler, A. E., Jamialahmadi, T., & Sahebkar, A. (2022) · EXCLI journal · doi:10.17179/excli2022-5482 · Cited by 34
“…therapy preserved cardiac microvascular barrier function and integrity and prevented DM-induced microvascular complications in the myocardium of diabetic animals by improving cardiac endothelial cell function by suppression of mitochondrial oxidative stress in treated mice (Zhou et al., 2018).”
On the wake of metformin: Do anti-diabetic SGLT2 inhibitors exert anti-aging effects?
Scisciola, L., Olivieri, F., Ambrosino, C., Barbieri, M., Rizzo, M. R., & Paolisso, G. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102131 · Cited by 34
“…revealed that empagliflozin inhibits endothelial cells senescence via an AMPK-mediated suppression of mitochondrial fission and a subsequent drop in mitochondrial ROS generation, in association with a suppression of ICAM-1 and VCAM-1 expression and restoration of eNOS activity (Zhou et al., 2018).”
BackgroundIordan, L., Gaiţă, L., Timar, R. Z., Avram, V. F., Sturza, A., & Timar, B. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137057 · Cited by 34
“…their increased urinary excretion of sodium, with an increased afflux to the macula densa and subsequent afferent arterioles vasoconstriction and lowering of the intraglomerular pressure, contribute to an additional decrease in albuminuria and decreased renal disease progression [50,52,167–169].”
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RetractedLiu, M., Wei, X., Zheng, Z., Xie, E., Yu, Q., Gao, Y., Ma, J., & Yang, L. (2024) · Molecular Medicine · doi:10.1186/s10020-024-00825-8 · Cited by 32
“It was reported that Empagliflozin can improve the symptoms of diabetic mice by activating AMPK and alleviating mitochondrial fission (Zhou et al. 2018).”
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Inhibition of EGFR-STAT3 attenuates cardiomyopathy in streptozotocin-induced type 1 diabetes
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SGLT2 inhibitors and AMPK: The road to cellular housekeeping?
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“19,20 Another promising effect SGLT2i exert on AMPK was described by Hawely and colleagues which significantly showed that Canagliflozin triggered AMPK in Human Embryonic Kidney, Moreover, this effect was associated by improvement in increased cellular ADP ‐ to ‐ ATP ratios.”
BackgroundWang, L., Zhang, X., Huang, X., Sha, X., Li, X., Zheng, J., Li, S., Wei, Z., & Wu, F. (2024) · The FASEB Journal · doi:10.1096/fj.202401299rr · Cited by 31
“11 Under physiological conditions, mitochondria undergoes constant division and fusion to maintain intracellular bioenergy metabolism and redox homeostasis.”
Cao, J., Wei, R., & Yao, S. (2018) · The Journal of Physiological Sciences · doi:10.1007/s12576-018-0634-4 · Cited by 31
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Effects of dapagliflozin and gliclazide on the cardiorenal axis in people with type 2 diabetes
van Bommel, E. J. M., Smits, M. M., Ruiter, D., Muskiet, M. H. A., Kramer, M. H. H., Nieuwdorp, M., Touw, D. J., Heerspink, H. J. L., Joles, J. A., & van Raalte, D. H. (2020) · Journal of Hypertension · doi:10.1097/hjh.0000000000002480 · Cited by 30
Geng, C., Wei, J., & Wu, C. (2018) · Acta Neurologica Belgica · doi:10.1007/s13760-018-0944-6 · Cited by 31
“Moreover, mitochondrial fission has been found to be involved in myocardial IR injury, endothelial inflammation damage, liver cancer migration, and endometriosis apoptosis [28, 44].”
RetractedLi, X., Li, Q., Jiang, X., Song, S., Zou, W., Yang, Q., Liu, S., Chen, S., & Wang, C. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01914-1 · Cited by 36
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RetractedThe Imbalance of Mitochondrial Fusion/Fission Drives High-Glucose-Induced Vascular Injury
Zheng, Y., Luo, A., & Liu, X. (2021) · Biomolecules · doi:10.3390/biom11121779 · Cited by 32
“For instance, Empagliflozin rescues diabetic myocardial microvascular injury via AMPK activation [50].”
BackgroundWang, J., Wang, X., Du, W., Xue, Z., Huang, W. J., Guan, Z., & Wang, H. (2021) · Cellular Signalling · doi:10.1016/j.cellsig.2021.110218 · Cited by 30
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“Coronary microcirculatory dysfunction is an important contributor to the occurrence, development and prognosis of cardiovascular disease [45,46].”
BackgroundNew insights into vascular aging: Emerging role of mitochondria function
Li, Y., Jin, X., Li, D. X., Lu, J. Z., Zhang, X., Yang, S., Zhao, Y., & Wu, M. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113954 · Cited by 30
Empagliflozin mitigates methotrexate-induced hepatotoxicity: Targeting ASK-1/JNK/Caspase-3 pathway
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CENP-F-dependent DRP1 function regulates APC/C activity during oocyte meiosis I
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“The impairment of mitochondrial morphology has been related to increased ROS levels in different experimental models [43, 46, 50, 71], including the use of hydrogen peroxide in neuroblastoma cells and cultured hippocampal neurons [50, 70].”
Zhu, P., Wang, J., Du, W., Ren, J. T., Zhang, Y., Xie, F., & Xu, G. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/6638244 · Cited by 29
“Haphazard mPTP opening time was reflected as duration of tetramethylrhodamine ethyl ester (TMRE) fluorescence intensity—its length is half of intensity from initial to residual fluorescence intensity [29].”
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“The dose of empagliflozin of 10 mg/kg was chosen based on the data from previously published pre-clinical studies [4, 7, 10].”
MethodTai, S., Zhou, Y., Fu, L., Ding, H., Zhou, Y., Yin, Z., Yang, R., Liu, Z., & Zhou, S. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e19152 · Cited by 28
“Previous studies have demonstrated that SGLT2i activates SIRT1 and suppresses Akt/mTOR, consequently promoting autophagy and reducing oxidative stress independent of effects on glucose [18,19].”
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Li, S.-S., Pan, L., Zhang, Z., Zhou, M.-D., Chen, X., Qian, L., Dai, M., Lu, J., Yu, Z.-M., Dang, S., et al. (2024) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2023.0031 · Cited by 30
“In the present study, we discovered that phosphorylation of AMPK decreased in STZ-induced diabetic cardiac tissues and HG-treated CFs, which was consistent with the previous studies [45].”
ResultHu, Y., Chen, X., Zhao, Q., Li, G., Zhang, H., Ma, Z., Yu, H., Zeng, Q., Zhang, H., & Xu, D. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.114613 · Cited by 28
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“Empagliflozin restores the AMP-to-ATP ratio leading to AMPK activation, triggering dynamin-related protein 1 (Drp1), a critical effector of mitochondrial fission [145].”
InfluentialMitochondrial Dysfunction in Endothelial Cells: A Key Driver of Organ Disorders and Aging
Grossini, E., Venkatesan, S., & Pour, M. M. O. (2025) · Antioxidants · doi:10.3390/antiox14040372 · Cited by 31
“Also, the therapeutic drug empagliflozin could maintain cardiac microvascular endothelial cells in diabetic patients by inhibiting mitochondrial fission through AMPK-dependent pathways [61].”
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CaMKII and GLUT1 in heart failure and the role of gliflozins
Trum, M., Wagner, S., Maier, L. S., & Mustroph, J. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165729 · Cited by 27
Quality Matters? The Involvement of Mitochondrial Quality Control in Cardiovascular Disease
Lin, K.-L., Chen, S., Lin, K.-J., Liou, C., Chuang, Y., Wang, P., Chuang, J., & Lin, T. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.636295 · Cited by 27
Chakraborty, P., Nattel, S., & Nanthakumar, K. (2020) · Heart Rhythm · doi:10.1016/j.hrthm.2020.03.025 · Cited by 27
Mui, D., & Zhang, Y. (2020) · Journal of Receptors and Signal Transduction · doi:10.1080/10799893.2020.1784938 · Cited by 27
Wang, X., Wang, Z., Liu, D., Jiang, H., Cai, C., Li, G., & Yu, G. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.839640 · Cited by 27
Li, N., Zhu, Q., Li, G.-Z., Wang, T., & Zhou, H. (2023) · World Journal of Diabetes · doi:10.4239/wjd.v14.i12.1862 · Cited by 26
Cai, C., Li, Z., Zheng, Z., Guo, Z., Li, Q., Deng, S., Shi, N., Zhou, H., Zhou, H., Guo, Z., et al. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.85767 · Cited by 25
“Similarly, the progression of diabetic cardiomyopathy can be delayed by mitophagy activation, linked to decreased mitochondrial oxidative stress and improved cardiomyocyte metabolism [43, 46, 75-77].”
BackgroundPotential Protective Mechanism in the Cardiac Microvascular Injury
Li, X., Hou, J., Du, J., Feng, J., Yang, Y., Shen, Y., Chen, S., Feng, J., Yang, D., Li, D., et al. (2018) · Hypertension · doi:10.1161/hypertensionaha.118.11035 · Cited by 26
Low‐glucose‐sensitive TRPC6 dysfunction drives hypoglycemia‐induced cognitive impairment in diabetes
He, C., Gao, P., Cui, Y., Li, Q., Li, Y., Lu, Z., Ma, H., Zhao, Y., Li, L., Sun, F., et al. (2020) · Clinical and Translational Medicine · doi:10.1002/ctm2.205 · Cited by 25
Nutri-stress, mitochondrial dysfunction, and insulin resistance—role of heat shock proteins
Jayashree, K., & Senthilkumar, G. P. (2022) · Cell Stress and Chaperones · doi:10.1007/s12192-022-01314-9 · Cited by 29
Song, P., Chen, T., Rui, S., Duan, X., Deng, B., Armstrong, D. G., Ma, Y., & Deng, W. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1081039 · Cited by 25
Maiorana, A., Tagliaferri, F., & Dionisi‐Vici, C. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1145111 · Cited by 25
“Several studies documented that empagliflozin activates the AMPK pathway in cardiomyocytes (65) and in a cardiac ischemia model in mice (64), hearts of lipopolysaccharide-treated mice (63), kidneys of diabetic mice (88), DPN of diabetic rats (45) as well as individual with T2DM (60) and in healthy conditions in vivo a…”
BackgroundNew insights on mitochondrial heteroplasmy observed in ovarian diseases
Zhou, Y., Jin, Y., Wu, T., Wang, Y., Dong, Y., Chen, P., Hu, C., Pan, N., Ye, C., Shen, L., et al. (2023) · Journal of Advanced Research · doi:10.1016/j.jare.2023.11.033 · Cited by 26
Wang, S., Bian, W., Zhen, J., Zhao, L., & Chen, W. (2019) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000678 · Cited by 25
SGLT2 inhibitors as a novel senotherapeutic approach
Yeşilyurt, Z. E., Qi, C., Wang, Y.-C., Simm, A., Deelen, L., Gasim, A. H. A., Lewis, F., & Ellison, G. M. (2025) · npj Aging · doi:10.1038/s41514-025-00227-y · Cited by 28
MAP4 as a New Candidate in Cardiovascular Disease
Li, L., Zhang, Q., Lei, X., Huang, Y., & Hu, J. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.01044 · Cited by 24
Xu, X., Cui, Y., Li, C., Wang, Y., Cheng, J., Chen, S., Sun, J., Ren, J., Yao, X., Gao, J., et al. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02459-x · Cited by 23
Shiraki, A., Oyama, J., Shimizu, T., Nakajima, T., Yokota, T., & Node, K. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175194 · Cited by 25
New insights into the molecular mechanisms of SGLT2 inhibitors on ventricular remodeling
Chen, Y., & Peng, D. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110072 · Cited by 28
Zhi, F., Zhang, Q., Liu, L., Chang, X., & Xu, H. (2023) · Cell Stress and Chaperones · doi:10.1007/s12192-023-01361-w · Cited by 24
“Consistent with impaired mitochondrial function, hyperglycemic exposure is also associated with a drop in the ATP/ADP ratio in diabetic hearts (Zhou et al. 2018).”
Song, J., Lu, C., Zhao, W., & Shao, X. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28701 · Cited by 24
“Bcl2 (1:1,000, #3498), caspase9 (1:1,000, #9504), Beclin1 (1:1,000, #3738), Mff (1:1,000, #86668), Bax (1:1,000, #2772), survivin (1:1,000, #2808) were purchased from Cell Signaling Technology (Danvers, MA) (Y. Q. Zhou et al., 2018).”
MethodRetractedWhat Is Cardiometabolic HFpEF and How Can We Study it Preclinically?
Daou, D., Tong, D., Schiattarella, G. G., Gillette, T. G., & Hill, J. A. (2025) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2025.04.009 · Cited by 32
Wang, B., Li, J., Bao, M., Chen, R., Li, H., Lu, B., Chen, M., Huang, D., Zhang, Y., Gao, F., et al. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/8882130 · Cited by 23
“DM and hyperglycemia can change endothelial cells structure and function, which contribute to CMEC dysfunction [5].”
BackgroundMethodYu, L., Dong, X., Li, N., Jiang, H., Zhao, J., Xu, Y., Xu, D., Xue, X., Zhou, Z., Huang, Y., et al. (2022) · Food & Function · doi:10.1039/d2fo00966h · Cited by 23
Wang, M., Wang, R., Xie, X., Sun, G., & Sun, X. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109143 · Cited by 23
Ding, L., Zhang, S., Li, Y., Li, Y., Liu, X., Xu, D., Zhao, K., Xu, C., Yu, B., Huang, X., et al. (2024) · Chemical Engineering Journal · doi:10.1016/j.cej.2024.150177 · Cited by 22
Empagliflozin rescues lifespan and liver senescence in naturally aged mice
Long, J., Ren, Z., Duan, Y., Tao, W., Li, X., Li, S., Li, K., Huang, Q., Chen, J., Yang, M., et al. (2024) · GeroScience · doi:10.1007/s11357-024-01250-9 · Cited by 23
“Studies have revealed that SGLT2 inhibitors promote AMPK activation via regulation of AMP/ATP and SIRT1 activation [27, 28].”
SIRT3‐Mediated Deacetylation of DRP1 K711 Prevents Mitochondrial Dysfunction in Parkinson's Disease
Ye, X., Tao, K., Wen, X., Feng, D., Mai, Z., Ding, H., Mao, H., Wang, M., Yang, Q., Xiang, J., et al. (2025) · Advanced Science · doi:10.1002/advs.202411235 · Cited by 27
Gaggini, M., Sabatino, L., Suman, A. F., Chatzianagnostou, K., & Vassalle, C. (2025) · Cells · doi:10.3390/cells14050387 · Cited by 29
“In T2D mice, empagliflozin restores AMP/ATP activation of AMPK, inducing Drp1S637 phosphorylation and decreasing Drp1S616 phosphorylation, which leads to the inhibition of mitochondrial fission, improving cardiac microvascular injury [121].”
Chu, K., Zhang, Z., Chu, Y., Xu, Y., Yang, W., & Guo, L. (2023) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2023.105632 · Cited by 22
Luo, L., Dong, B., Zhang, J., Liu, X., Liu, X., Zhou, Z. C., He, J., Zhang, X., Chen, L., & Xia, W. (2023) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2023.05.094 · Cited by 22
Roles of mitochondrial dynamics and mitophagy in diabetic myocardial microvascular injury
Wang, T., Wang, X., Fu, T., Ma, Y., Wang, Q., Zhang, S., Zhang, X., Zhou, H., Chang, X., & Tong, Y. (2023) · Cell Stress and Chaperones · doi:10.1007/s12192-023-01384-3 · Cited by 22
“SGLT2i treatment was also reported to inhibit mitochondrial fission in cardiac microvascular endothelial cells by suppressing the DNA-dependent protein kinase catalytic subunit/Fis1 pathway (Zhou et al. 2018; Zou et al. 2022).”
Sang, X., Xiao, J., Liu, Q., Zhu, R., Dai, J., Zhang, C., Yu, H., Yang, S., & Zhang, B. (2020) · The FASEB Journal · doi:10.1096/fj.202000781rrr · Cited by 22
The changes of cardiac energy metabolism with sodium-glucose transporter 2 inhibitor therapy
Su, S., Ji, X., Li, T., Teng, Y., Wang, B., Han, X., & Zhao, M. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1291450 · Cited by 25
Mitochondrial Quality Control Mechanisms during Diabetic Cardiomyopathy
Ketenci, M., Zablocki, D., & Sadoshima, J. (2022) · JMA Journal · doi:10.31662/jmaj.2022-0155 · Cited by 21
“It leads to improved cardiac nutrient and oxygen supply and increased resistance of cardiac microvascular cells to hyperglycemic insult ((66)).”
Background
Metadata
- Authors
- Zhou, H., Wang, S., Zhu, P., Hu, S., Chen, Y., & Ren, J.
- Affiliations
- Chinese PLA General Hospital (CN)
- University of Wyoming (US)
- Corresponding author
- Zhou, Hao
- Chen, Yundai
- Ren, Jun
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 15
- Pages
- 335-346
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC5756062
- OpenAlex
- W2777514005
- Cited by
- 550
- References
- 63
- Citations by year
- 2026: 34 · 2025: 53 · 2024: 87 · 2023: 71 · 2022: 71 · 2021: 65 · 2020: 63 · 2019: 53 · 2018: 50
- FWCI
- 35.91
- Type
- journal article
- Language
- en
- Update notices
- erratum (2024-05-01)
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81441008, 81030002, 81102079, 81270186)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- empagliflozin, SGLT2 inhibitors, diabetic cardiomyopathy, mitochondrial fission, AMPK, Drp1 phosphorylation, endothelial barrier function, endothelial cell senescence, mitochondrial reactive oxygen species, oxidative stress, angiogenesis, endothelial cell migration, F-actin depolymerization, eNOS phosphorylation, type 2 diabetes
- MeSH terms
- AMP-Activated Protein Kinase Kinases, Animals, Benzhydryl Compounds, Diabetes Mellitus, Type 2, Glucosides, Heart Injuries, Humans, Mitochondria, Protein Kinases, Endothelial Cells, Mice, Mitochondrial Dynamics
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