Of mice and men: models and mechanisms of diabetic cardiomyopathy

Riehle, Christian; Bauersachs, Johann

doi:10.1007/s00395-018-0711-0

Cited by 142 publications

(130 citation statements)

References 236 publications

(281 reference statements)

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“…For MDA and SOD measurement (Y. Zhang, Zou, et al, ), the samples were rinsed with PBS and then homogenized and sonicated in lysis buffer on ice (B. Zhang, Hou, et al, ). After sonication, the lysed tissues were centrifuged at 10,000 g for 10 min to remove debris (Riehle & Bauersachs, ). For GSH measurement, liver tissues were homogenized through three freeze‐thaw cycles (Y. Zhang, Zou, et al, ), and then the tissue suspension was centrifuged at 12,000 rpm for 5 min at 4°C (Yachi et al, ).…”

Section: Methodsmentioning

confidence: 99%

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PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK–CREB–Mfn2‐mitophagy signaling pathway

Wang

Zhao

et al. 2019

Journal Cellular Physiology

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Atherosclerosis (AS) is a major pathogenic factor in patients with cardiovascular diseases, and endothelial dysfunction (ED) plays a primary role in the occurrence and development of AS. In our study, we attempted to evaluate the role of phosphatase and tensin homolog (PTEN) in endothelial cell apoptosis under oxidized low-density lipoprotein (ox-LDL) stimulation and identify the associated mechanisms. The results of our study demonstrated that ox-LDL induced human umbilical vein endothelial cell (HUVEC) death via mitochondrial apoptosis, as evidenced by reduced mitochondrial potential, increased mitochondria permeability transition pore opening, cellular calcium overload, and caspase-9/-3 activation. In addition, ox-LDL also suppressed cellular energy production via downregulating the mitochondrial respiratory complex. Moreover, ox-LDL impaired HUVECs migration. Western blot analysis showed that PTEN expression was upregulated after exposure to ox-LDL and knockdown of PTEN could attenuate ox-LDL-mediated endothelial cell damage. Furthermore, we found that ox-LDL impaired mitophagy activity, whereas PTEN deletion could improve mitophagic flux and this effect relied on the activity of the AMPactivated protein kinase (AMPK)-cAMP-response element-binding protein (CREB)-Mitofusin-2 (Mfn2) axis. When the AMPK-CREB-Mfn2 pathway was inhibited, PTEN deletion-associated HUVECs protection was significantly reduced, suggesting that the AMPK-CREB-Mfn2-mitophagy axis is required for PTEN deletion-mediated endothelial cell survival under ox-LDL. Taken together, our results indicate that ox-LDL-induced endothelial cell damage is associated with PTEN overexpression, and inhibition of PTEN could promote endothelial survival via activating the AMPK-CREB-Mfn2-mitophagy signaling pathway. K E Y W O R D S AMPK-CREB-Mfn2 signaling pathway, endothelial cell dysfunction, Mfn2, mitophagy, ox-LDL, PTEN

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Section: Methodsmentioning

confidence: 99%

“…Zhang, Hou, et al, 2018). After sonication, the lysed tissues were centrifuged at 10,000g for 10 min to remove debris (Riehle & Bauersachs, 2018).…”

Section: Measurement Of Malondialdehyde (Mda) Glutathione (Gsh) Amentioning

confidence: 99%

PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK–CREB–Mfn2‐mitophagy signaling pathway

Wang

Zhao

et al. 2019

Journal Cellular Physiology

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“…Diabetic cardiomyopathy (DCM) is mainly characterized by a cardiac dysfunction observed in patients with diabetes mellitus. Generally, DCM occurs in the absence of all other cardiovascular diseases, including coronary artery disease, hypertensive heart disease, valvular heart disease, and congenital heart disease (Wang-Soo and Jaetaek, 2017;Riehle and Bauersachs, 2018;Filardi et al, 2019). Pathologically, diabetes-induced cardiac fibrosis is a central step, causing left ventricular hypertrophy (LVH), diastolic and systolic dysfunction.…”

Section: Introductionmentioning

confidence: 99%

LncRNA-MIAT-Mediated miR-214-3p Silencing Is Responsible for IL-17 Production and Cardiac Fibrosis in Diabetic Cardiomyopathy

Mai

et al. 2020

Front. Cell Dev. Biol.

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As an important complication of diabetes mellitus, diabetic cardiomyopathy (DCM) is characterized by a silent development in its earlier stage and a deficient cardiomyocyte contractility in its late stage. So far, little advance has been achieved to reverse this pathological change. LncRNAs are defined as a large cluster of RNAs without the function of encoding proteins, but have the capacity in controlling gene expression. Interleukin-17 (IL-17), a proinflammatory cytokine, is a key regulator of host inflammation. Clinically, it plays a crucial role in the pathogenesis of cardiac interstitial fibrosis. In this study, we reported that high glucose-induced lncRNA-MIAT upregulation is responsible for proinflammatory IL-17 production in cardiomyocytes. The underlying mechanism is likely due to that lncRNA-MIAT specific attenuates miR-214-3p-mediated inhibitory effect on IL-17 expression. As a result, attenuated IL-17 expression significantly ameliorate cardiac fibrosis, followed by improvement of cardiac contractility. Taken together, our study first suggests that lncRNA-MIAT plays a key role in DCM and targeting lncRNA-MIAT may become a potential strategy to treat DCM.

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“…Both structural and functional mitochondrial impairment have been reported in the diabetic heart, in both animals and humans. [46][47][48][49][50] Mitochondrial biogenesis is a complex dynamic process that regulates the composition and content of mitochondria in diverse tissues. However, the ways in which diabetes can influence the highly regulated steps in mitochondrial biogenesis are incompletely understood.…”

Section: Discussionmentioning

confidence: 99%

MiR‐144 protects the heart from hyperglycemia‐induced injury by regulating mitochondrial biogenesis and cardiomyocyte apoptosis

Tao

Huang

et al. 2019

FASEB j.

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contributed equally to this work.Abbreviations: AMPK, adenosine monophosphate-activated protein kinase; ATP, adenosine triphosphate; A, atrial contraction; BSA, bovine serum albumin; CAD, coronary artery disease; DCM, diabetic cardiomyopathy; DMEM, Dulbecco's modified Eagle's medium; E, peak filling rates of the early filling phase; e', early diastolic lengthening mitral valve flow velocity; EF, ejection fraction; eNOs, endothelial NO synthase; FBS, fetal bovine serum; FS, left ventricular fractional shortening; Gated-MPI, Gated-myocardial perfusion imaging; HG, high glucose; LVDD, left ventricle diastolic dysfunction; LVIDd, left ventricular internal dimension-diastole; LVIDs, left ventricular internal dimension-systole; LV mass, left ventricular mass; miRNA, microRNA; mtDNA, mitochondrial DNA; NC, negative control; Nox, nicotinamide adenine dinucleotide phosphate oxidase; NRF1, nuclear respiratory factor 1; OXPHOS, oxidative phosphorylation; PAK, p21-activated protein kinase; PBD, p21-binding domain; PFA, paraformaldehyde; PGC-1α, peroxisome proliferator-activated receptor γ coactivator 1α; qRT-PCR, Quantitative real-time polymerase chain reactions; ROC, receiver-operator characteristic; ROS, reactive oxygen species; SIRT1, silent information regulator 1; SPF, specific pathogen-free; STZ, streptozotocin; TCA, , tricarboxylic acid; T2DM, type 2 diabetes; TFAM, mitochondrial transcription factor A; TEM, transmission electron microscope; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP in situ nick end labeling; VADT, veterans affairs diabetes trial; WGA, wheat germ agglutinin. AbstractSeveral lines of evidence have revealed the potential of microRNAs (miRNAs, miRs) as biomarkers for detecting diabetic cardiomyopathy, although their functions in hyperglycemic cardiac dysfunction are still lacking. In this study, mitochondrial biogenesis was markedly impaired induced by high glucose (HG), as evidenced by dysregulated mitochondrial structure, reduced mitochondrial DNA contents, and biogenesis-related mRNA levels, accompanied by increased cell apoptosis. MiR-144 was identified to be decreased in HG-induced cardiomyocytes and in streptozotocin (STZ)-challenged heart samples. Forced miR-144 expression enhanced mitochondrial biogenesis and suppressed cell apoptosis, while miR-144 inhibition exhibited the opposite results. Rac-1 was identified as a target gene of miR-144. Decreased Rac-1 levels activated AMPK phosphorylation and PGC-1α deacetylation, leading to increased mitochondrial biogenesis and reduced cell apoptosis. Importantly, the systemic neutralization of miR-144 attenuated mitochondrial disorder and ventricular dysfunction following STZ treatment. Additionally, plasma miR-144 decreased markedly in diabetic patients with cardiac dysfunction. The receiver-operator characteristic curve showed that plasma miR-144 could specifically predict diabetic patients developing cardiac dysfunction. In conclusion, this study provides strong 2174 |

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Of mice and men: models and mechanisms of diabetic cardiomyopathy

Cited by 142 publications

References 236 publications

PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK–CREB–Mfn2‐mitophagy signaling pathway

PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK–CREB–Mfn2‐mitophagy signaling pathway

LncRNA-MIAT-Mediated miR-214-3p Silencing Is Responsible for IL-17 Production and Cardiac Fibrosis in Diabetic Cardiomyopathy

MiR‐144 protects the heart from hyperglycemia‐induced injury by regulating mitochondrial biogenesis and cardiomyocyte apoptosis

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