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Pubblicazioni recenti - diabetic cardiomyopathy
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The Systolic and Diastolic Cardiac Function of Patients With Type 2 Diabetes Mellitus: An Evaluation of Left Ventricular Strain and Torsion Using Conventional and Speckle Tracking Echocardiography.
Front Physiol2021 ;12():726719. doi: 10.3389/fphys.2021.726719.
Yang Qing-Mei, Fang Jian-Xiu, Chen Xiao-Yan, Lv Hong, Kang Chun-Song,
Abstract
This study aimed to quantify left ventricular (LV) myocardial strain and torsion in patients with type 2 diabetes mellitus (T2DM) and evaluate their systolic and diastolic function using conventional and speckle tracking echocardiography. Forty-seven patients with T2DM were divided into a group without microvascular complications (the DM A group) and a group with microvascular complications (the DM B group), while another 27 healthy participants acted as the control group. All the participants had had an echocardiography examination. All the original data were imported into EchoPAC workstation for the analysis and quantification of LV strain and torsion. Compared with the control group, the LV end-diastolic volume, end-systolic volume, and ejection fraction of the DM A and DM B groups showed no significant differences, but the global longitudinal strain and the global circular strain were reduced in the DM B group. There were significant differences in the left ventricular relative wall thickness (RWT), left ventricular mass index (LVMI), the early mitral valvular blood flow velocity peak/left ventricular sidewall mitral annulus late peak velocity, left ventricular sidewall mitral annulus early peak velocity/left ventricular sidewall mitral annulus late peak velocity, isovolumic relaxation time, peak twisting, peak untwisting velocity (PUV), untwisting rate (UntwR), time peak twisting velocity (TPTV), and time peak untwisting velocity (TPUV) between the DM A, DM B, and control groups. While the peak twisting velocity (PTV) was slower in the DM B group compared with the control group, the RWT, PTV, PUV, UntwR, TPTV, and TPUV in the DM B group were significantly different from the DM A group. The cardiac function of patients with T2DM in its early stages, when there are no microvascular complications, could be monitored with the analysis of two-dimensional strain and torsion.
Copyright © 2022 Yang, Fang, Chen, Lv and Kang.
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Protective effect of glucagon-like peptide-1 mediated by ultrasound microbubbles on myocardial injury in rats with diabetic cardiomyopathy.
Bioengineered2022 Feb;13(2):3251-3261. doi: 10.1080/21655979.2021.2022270.
Liu Yanjie, Chen Li, Wu Hao, Zhang Hebin,
Abstract
ABBREVIATIONS:
Ultrasound-targeted microbubble destruction, UTMD; glucagon-like peptide-1 receptor, GLP-1R; diabetic cardiomyopathy, DCM; Goto-Kakizaki, GK; velocity vector imaging, VVI; left ventricular end-diastolic diameter LVIDd; left ventricular end-systolic diameter, LvIDs; left ventricular end-diastolic pressure, LVEDP; fractional shortening, LVFs; left ventricular ejection fraction, LVEF; mean peak radial velocity, Vs; radial strain, Sr; radial strain rate, SRr; superoxide dismutase, SOD; malondialdehyde, MDA; glutathione peroxidase, GSH-Px; peroxisome proliferator-activated receptor-?, PPAR-?; nuclear transcription factor ?B, NF-?B; insulin resistance, IR; total cholesterol, TC; total triglycerides, TG; creatine kinase, CK; lactate dehydrogenase, LDH; cardiac troponin I, cTnI; collagen volume fraction, CVF; Hematoxylin eosin, H&E.
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Hydrogen sulfide postconditioning rendered cardioprotection against myocardial ischemia-reperfusion injury is compromised in rats with diabetic cardiomyopathy.
Microvasc Res2022 Jan;141():104322. doi: S0026-2862(22)00012-7.
Ansari Mahalakshmi, Prem Priyanka N, Kurian Gino A,
Abstract
The present study aimed to investigate the efficacy of hydrogen sulfide (HS) post-conditioning (HPOC) against ischemia-reperfusion (I/R) challenged diabetic rat hearts with or without cardiomyopathy using the Langendorff perfusion system. Male Wistar rats were randomly divided into different groups such as normal, diabetes mellitus (DM), and diabetic cardiomyopathy (DCM). Hearts from these groups were subjected to normal perfusion, I/R, and HPOC and were analyzed for cardiac physiology, cardiomyocyte injury, mitochondrial function, oxidative stress, and HS metabolism. The results showed that HPOC protocol reduced the cardiac injury and improved the haemodynamics in normal and DM effectively, but not in DCM (RPP in mmHg*beats/min*10: HPOC- 32 ± 2, DM-HPOC-19 ± 1, DCM-HPOC-6 ± 2, LVDP in mmHg: HPOC- 96 ± 3, DM-HPOC-73 ± 2, DCM-HPOC-50 ± 3). DCM rats at the basal level exhibited perturbed myocardial architecture, mitochondrial dysfunction, and impaired glycolytic flux that failed to improve by HPOC treatment after I/R. HPOC exhibited a nominal improvement in the gene expression and activities of the HS metabolizing enzymes such as cystathionine beta-synthase, rhodanese, and cystathionine-gamma-lyase in DCM hearts. Collectively, our results suggest that altered myocardial architecture along with exacerbated oxidative stress and mitochondrial dysfunction contribute towards the failure of HPOC cardioprotection against I/R-induced myocardial tissue injury in DCM.
Copyright © 2022 Elsevier Inc. All rights reserved.
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Krill Oil Inhibits NLRP3 Inflammasome Activation in the Prevention of the Pathological Injuries of Diabetic Cardiomyopathy.
Nutrients2022 Jan;14(2):. doi: 368.
Sun Xuechun, Sun Xiaodan, Meng Huali, Wu Junduo, Guo Xin, Du Lei, Wu Hao,
Abstract
Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM), resulting in high mortality. Myocardial fibrosis, cardiomyocyte apoptosis and inflammatory cell infiltration are hallmarks of DCM, leading to cardiac dysfunction. To date, few effective approaches have been developed for the intervention of DCM. In the present study, we investigate the effect of krill oil (KO) on the prevention of DCM using a mouse model of DM induced by streptozotocin and a high-fat diet. The diabetic mice developed pathological features, including cardiac fibrosis, apoptosis and inflammatory cell infiltration, the effects of which were remarkably prevented by KO. Mechanistically, KO reversed the DM-induced cardiac expression of profibrotic and proinflammatory genes and attenuated DM-enhanced cardiac oxidative stress. Notably, KO exhibited a potent inhibitory effect on NLR family pyrin domain containing 3 (NLRP3) inflammasome that plays an important role in DCM. Further investigation showed that KO significantly upregulated the expression of Sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor-? coactivator 1? (PGC-1?), which are negative regulators of NLRP3. The present study reports for the first time the preventive effect of KO on the pathological injuries of DCM, providing SIRT3, PGC-1? and NLRP3 as molecular targets of KO. This work suggests that KO supplementation may be a viable approach in clinical prevention of DCM.
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Seipin Deficiency as a Model of Severe Adipocyte Dysfunction: Lessons from Rodent Models and Teaching for Human Disease.
Int J Mol Sci2022 Jan;23(2):. doi: 740.
Magré Jocelyne, Prieur Xavier,
Abstract
Obesity prevalence is increasing worldwide, leading to cardiometabolic morbidities. Adipocyte dysfunction, impairing white adipose tissue (WAT) expandability and metabolic flexibility, is central in the development of obesity-related metabolic complications. Rare syndromes of lipodystrophy characterized by an extreme paucity of functional adipose tissue should be considered as primary adipocyte dysfunction diseases. Berardinelli-Seip congenital lipodystrophy (BSCL) is the most severe form with a near absence of WAT associated with cardiometabolic complications such as insulin resistance, liver steatosis, dyslipidemia, and cardiomyopathy. Twenty years ago, mutations in the gene have been identified as the cause of BSCL in human. encodes seipin, an endoplasmic reticulum (ER) anchored protein whose function was unknown back then. Studies of seipin knockout mice or rats demonstrated how seipin deficiency leads to severe lipodystrophy and to cardiometabolic complications. At the cellular levels, seipin is organized in multimers that are particularly enriched at ER/lipid droplet and ER/mitochondria contact sites. Seipin deficiency impairs both adipocyte differentiation and mature adipocyte maintenance. Experiments using adipose tissue transplantation in seipin knockout mice and tissue-specific deletion of seipin have provided a large body of evidence that liver steatosis, cardiomyopathy, and renal injury, classical diabetic complications, are all consequences of lipodystrophy. Rare adipocyte dysfunctions such as in BSCL are the key paradigm to unravel the pathways that control adipocyte homeostasis. The knowledge gathered through the study of these pathologies may bring new strategies to maintain and improve adipose tissue expandability.
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Mesenchymal Stem Cell Therapy in Diabetic Cardiomyopathy.
Cells2022 Jan;11(2):. doi: 240.
da Silva Jaqueline S, Gonçalves Renata G J, Vasques Juliana F, Rocha Bruna S, Nascimento-Carlos Bianca, Montagnoli Tadeu L, Mendez-Otero Rosália, de Sá Mauro P L, Zapata-Sudo Gisele,
Abstract
The incidence and prevalence of diabetes mellitus (DM) are increasing worldwide, and the resulting cardiac complications are the leading cause of death. Among these complications is diabetes-induced cardiomyopathy (DCM), which is the consequence of a pro-inflammatory condition, oxidative stress and fibrosis caused by hyperglycemia. Cardiac remodeling will lead to an imbalance in cell survival and death, which can promote cardiac dysfunction. Since the conventional treatment of DM generally does not address the prevention of cardiac remodeling, it is important to develop new alternatives for the treatment of cardiovascular complications induced by DM. Thus, therapy with mesenchymal stem cells has been shown to be a promising approach for the prevention of DCM because of their anti-apoptotic, anti-fibrotic and anti-inflammatory effects, which could improve cardiac function in patients with DM.
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Methazolamide Attenuates the Development of Diabetic Cardiomyopathy by Promoting ?-Catenin Degradation in Type 1 Diabetic Mice.
Diabetes2022 Jan;():. doi: db210506.
Chen Xiaoqing, Li Yilang, Yuan Xun, Yuan Wenchang, Li Conglin, Zeng Yue, Lian Yuling, Qiu Xiaoxia, Qin Yuan, Zhang Guiping, Liu Xia-Wen, Luo Chengfeng, Luo Jiandong, Hou Ning,
Abstract
Methazolamide (MTZ), a carbonic anhydrase inhibitor, has been shown to inhibit cardiomyocyte hypertrophy and exert a hypoglycemic effect in patients with type 2 diabetes mellitus and diabetic db/db mice. However, whether MTZ has a cardioprotective effect in the setting of diabetic cardiomyopathy is not clear. We investigated the effects of MTZ in a mouse model of streptozotocin-induced type 1 diabetes mellitus (T1DM). Diabetic mice received MTZ by intragastric gavage (10, 25, or 50 mg/kg; daily for 16 weeks). In the diabetic group, MTZ significantly reduced both random and fasting blood glucose levels and improved glucose tolerance in a dose-dependent manner. MTZ ameliorated T1DM-induced changes in cardiac morphology and dysfunction. Mechanistic analysis revealed that MTZ blunted T1DM-induced enhanced expression of ?-catenin. Similar results were observed in neonatal rat cardiomyocytes (NRCMs) and adult mouse cardiomyocytes treated with high glucose or Wnt3a (a ?-catenin activator). There was no significant change in ?-catenin mRNA levels in cardiac tissues or NRCMs. MTZ-mediated ?-catenin downregulation was recovered by MG132, a proteasome inhibitor. Immunoprecipitation and immunofluorescence analyses showed augmentation of AXIN1-?-catenin interaction by MTZ in T1DM hearts and in NRCMs treated with Wnt3a; thus, MTZ may potentiate AXIN1-?-catenin linkage to increase ?-catenin degradation. Overall, MTZ may alleviate cardiac hypertrophy by mediating AXIN1-?-catenin interaction to promote degradation and inhibition of ?-catenin activity. These findings may help inform novel therapeutic strategy to prevent heart failure in patients with diabetes mellitus.
© 2022 by the American Diabetes Association.
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CircularRNA circ_0071269 knockdown protects against from diabetic cardiomyopathy injury by microRNA-145/gasdermin A axis.
Bioengineered2022 Feb;13(2):2398-2411. doi: 10.1080/21655979.2021.2024688.
Fu Lanfang, Zhang Juyun, Lin Zhu, Li Yi, Qin Guijun,
Abstract
Circular RNAs (circRNAs) are involved in the development and progression of diabetic cardiomyopathy (DCM). However, the specific function and underlying mechanism of circ_0071269 in DCM remains unclear. In our study, mRNA and miRNA expression was detected by real-time quantitative PCR (qRT-PCR). RNase R and actinomycin D treatment were applied to test the characteristics of circ_0071269. Cell Counting Kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) and enzyme-linked immunosorbent assay (ELISA) kits were performed to determine the cell viability, cell LDH content and interleukin (IL)-1? and IL-18 levels, respectively. Cell death rate was determined by Flow cytometry, and Western blotting was for the protein expression levels. In addition, luciferase reporter and RNA pull-down assays were performed to confirm the binding relationship between miR-145 and circ_0071269 or gasdermin A (GSDMA). Echocardiography, Hematoxylin and Eosin (HE) Staining, and Immunohistochemical (IHC) Staining were performed to evaluate myocardial damage . We found that circ_0071269 was significantly overexpressed in H9c2 cells upon treatment with high glucose. Knockdown of circ_0071269 promoted cell viability and inhibited the inflammatory response, cytotoxicity, and pyroptosis of H9c2 cells . Moreover, circ_0071269 sponges miR-145 to upregulate GSDMA. A miR-145 inhibitor antagonized the effects of circ_0071269 knockdown on the cellular functions of H9c2 cells, while the effects of miR-145 were abrogated by the overexpression of GSDMA. Meanwhile, knockdown of circ_0071269 attenuated cardiac dysfunction of DM mice. Hence, circ_0071269 may promote the development of DCM through the miR-145/GSDMA axis and thus provide a novel marker for the treatment of DCM.
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miR-30a-5p inhibits the proliferation and collagen formation of cardiac fibroblasts in diabetic cardiomyopathy.
Can J Physiol Pharmacol2022 Jan;():1-9. doi: 10.1139/cjpp-2021-0280.
Yang Xiao-Xu, Zhao Zhen-Yu,
Abstract
Cardiac fibrosis is one of the major pathological characteristics of diabetic cardiomyopathy (DCM). MicroRNAs (miRNAs, miRs) have been identified as key regulators in the progression of cardiac fibrosis. This study aimed to investigate the role of in DCM and the underlying mechanism. The rat model of diabetes mellitus (DM) was established by streptozotocin injection, and the rat primary cardiac fibroblasts (CFs) were isolated from cardiac tissue and then treated with high glucose (HG). MTT assay was performed to assess the viability of CFs. Dual-luciferase reporter gene assay was conducted to verify the interaction between and . The expression of was downregulated in the myocardial tissues of DM rats and HG-stimulated CFs. Overexpression of reduced levels and inhibited collagen formation in HG-stimulated CFs and DM rats, as well as decreased the proliferation of CFs induced by HG. was a target of and its expression was inhibited by . Furthermore, the simultaneous overexpression of and reversed the effect of overexpression alone in CFs. Our results indicated that reduced expression and also induced a decrease in proliferation and collagen formation in DCM.
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Ginsenoside Rb1 Protects Against Diabetic Cardiomyopathy by Regulating the Adipocytokine Pathway.
J Inflamm Res2022 ;15():71-83. doi: 10.2147/JIR.S348866.
Zhang Chenyang, Han Meixin, Zhang Xuelian, Tong Hongna, Sun Xiaobo, Sun Guibo,
Abstract
Purpose:
Obesity and diabetes are often accompanied by chronic inflammation and insulin resistance, which lead to complications such as diabetic cardiomyopathy. Ginsenoside Rb1 has been used to treat diabetes and obesity and reduce inflammation as well as risk of heart diseases. However, the role of ginsenoside Rb1 in treating diabetic cardiomyopathy remains unclear.
Methods:
Diabetic mice were administered ginsenoside Rb1 for 12 weeks, and their body weight, body fat, and blood glucose levels as well as and serum insulin, lipids, and adipocytokine levels were assessed. Lipid accumulation, pathological morphology of the adipose tissue, liver, and heart were examined. Western blot and qRT-PCR were performed to investigate the molecular changes in response to ginsenoside Rb1 treatment.
Results:
Ginsenoside Rb1 treatment significantly reduced body weight and body fat, attenuated hyperglycemia and hyperlipidemia, and ameliorated insulin resistance and abnormal levels of adipocytokines in diabetic mice. In addition, lipid accumulation and inflammation reduced while the functions of heart improved in the ginsenoside Rb1-treated group. Furthermore, antioxidant function improved in the ginsenoside Rb1-treated diabetic hearts. PCR and Western blotting analyses revealed that the lipid-lowering effect of ginsenoside Rb1 and the resulting improvement of cardiac function could be attributed to the adipocytokine pathway, which promoted energy homeostasis and alleviated cardiac dysfunction.
Conclusion:
Ginsenoside Rb1 lowered lipid levels in a adipocytokine-mediated manner and attenuated hyperglycemia/hyperlipidemia-induced oxidative stress, hypertrophy, inflammation, fibrosis, and apoptosis in cardiomyocytes.
© 2022 Zhang et al.
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METTL14 suppresses pyroptosis and diabetic cardiomyopathy by downregulating TINCR lncRNA.
Cell Death Dis2022 01;13(1):38. doi: 10.1038/s41419-021-04484-z.
Meng Liping, Lin Hui, Huang Xingxiao, Weng Jingfan, Peng Fang, Wu Shengjie,
Abstract
N6-methyladenosine (m6A) is one of the most important epigenetic regulation of RNAs, such as lncRNAs. However, the underlying regulatory mechanism of m6A in diabetic cardiomyopathy (DCM) is very limited. In this study, we sought to define the role of METTL14-mediated m6A modification in pyroptosis and DCM progression. DCM rat model was established and qRT-PCR, western blot, and immunohistochemistry (IHC) were used to detect the expression of METTL14 and TINCR. Gain-and-loss functional experiments were performed to define the role of METTL14-TINCR-NLRP3 axis in pyroptosis and DCM. RNA pulldown and RNA immunoprecipitation (RIP) assays were carried out to verify the underlying interaction. Our results showed that pyroptosis was tightly involved in DCM progression. METTL14 was downregulated in cardiomyocytes and hear tissues of DCM rat tissues. Functionally, METTL14 suppressed pyroptosis and DCM via downregulating lncRNA TINCR, which further decreased the expression of key pyroptosis-related protein, NLRP3. Mechanistically, METTL14 increased m6A methylation level of TINCR gene, resulting in its downregulation. Moreover, the m6A reader protein YTHDF2 was essential for m6A methylation and mediated the degradation of TINCR. Finally, TINCR positively regulated NLRP3 by increasing its mRNA stability. To conclude, our work revealed the novel role of METTL14-mediated m6A methylation and lncRNA regulation in pyroptosis and DCM, which could help extend our understanding the epigenetic regulation of pyroptosis in DCM progression.
© 2021. The Author(s).
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Glucose-dependent insulinotropic polypeptide inhibits cardiac hypertrophy and fibrosis in diabetic mice via suppression of TGF-?2.
Diab Vasc Dis Res;18(2):1479164121999034. doi: 10.1177/1479164121999034.
Hiromura Munenori, Mori Yusaku, Terasaki Michishige, Kushima Hideki, Saito Tomomi, Osaka Naoya, Yashima Hironori, Ohara Makoto, Fukui Tomoyasu, Matsui Takanori, Yamagishi Sho-Ichi,
Abstract
Diabetic cardiomyopathy is associated with an increased risk for heart failure and death in patients with diabetes. We investigated here whether and how GIP attenuated cardiac hypertrophy and fibrosis in diabetic mice with obesity. Diabetic db/db mice at 7?weeks old were infused with vehicle or GIP (50?nmol/kg/day) for 6?weeks, and hearts were collected for histological and RT-PCR analyzes. Cardiomyocytes isolated from neonatal mice were incubated with or without 300?nM [D-Ala2]-GIP, 30?mM glucose, or 100??g/mL advanced glycation end products (AGEs) for RT-PCR and lucigenin assays. Compared with non-diabetic mice, diabetic mice exhibited larger left ventricle wall thickness and cardiomyocyte sizes and more fibrotic areas in association with up-regulation of myosin heavy chain ? (?-Mhc) and transforming growth factor-beta2 (Tgf-?2) mRNA levels, all of which were inhibited by GIP infusion. High glucose increased NADPH oxidase-driven superoxide generation and up-regulated ?-Mhc, Tgf-?2, and receptor for AGEs mRNA levels in cardiomyocytes, and augmented the AGE-induced ?-Mhc gene expression. [D-Ala2]-GIP attenuated all of the deleterious effects of high glucose and/or AGEs on cardiomyocytes. Our present findings suggest that GIP could inhibit cardiac hypertrophy and fibrosis in diabetic mice via suppression of TGF-?2.
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New insights into the role of melatonin in diabetic cardiomyopathy.
Pharmacol Res Perspect2022 02;10(1):e00904. doi: 10.1002/prp2.904.
Huang Keming, Luo Xianling, Zhong Yi, Deng Li, Feng Jian,
Abstract
Diabetic cardiovascular complications and impaired cardiac function are considered to be the main causes of death in diabetic patients worldwide, especially patients with type 2 diabetes mellitus (T2DM). An increasing number of studies have shown that melatonin, as the main product secreted by the pineal gland, plays a vital role in the occurrence and development of diabetes. Melatonin improves myocardial cell metabolism, reduces vascular endothelial cell death, reverses microcirculation disorders, reduces myocardial fibrosis, reduces oxidative and endoplasmic reticulum stress, regulates cell autophagy and apoptosis, and improves mitochondrial function, all of which are the characteristics of diabetic cardiomyopathy (DCM). This review focuses on the role of melatonin in DCM. We also discuss new molecular findings that might facilitate a better understanding of the underlying mechanism. Finally, we propose potential new therapeutic strategies for patients with T2DM.
© 2022 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.
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Novel Insights Into the Pathogenesis of Diabetic Cardiomyopathy and Pharmacological Strategies.
Front Cardiovasc Med2021 ;8():707336. doi: 10.3389/fcvm.2021.707336.
Muñoz-Córdova Felipe, Hernández-Fuentes Carolina, Lopez-Crisosto Camila, Troncoso Mayarling F, Calle Ximena, Guerrero-Moncayo Alejandra, Gabrielli Luigi, Chiong Mario, Castro Pablo F, Lavandero Sergio,
Abstract
Diabetic cardiomyopathy (DCM) is a severe complication of diabetes developed mainly in poorly controlled patients. In DCM, several clinical manifestations as well as cellular and molecular mechanisms contribute to its phenotype. The production of reactive oxygen species (ROS), chronic low-grade inflammation, mitochondrial dysfunction, autophagic flux inhibition, altered metabolism, dysfunctional insulin signaling, cardiomyocyte hypertrophy, cardiac fibrosis, and increased myocardial cell death are described as the cardinal features involved in the genesis and development of DCM. However, many of these features can be associated with broader cellular processes such as inflammatory signaling, mitochondrial alterations, and autophagic flux inhibition. In this review, these mechanisms are critically discussed, highlighting the latest evidence and their contribution to the pathogenesis of DCM and their potential as pharmacological targets.
Copyright © 2021 Muñoz-Córdova, Hernández-Fuentes, Lopez-Crisosto, Troncoso, Calle, Guerrero-Moncayo, Gabrielli, Chiong, Castro and Lavandero.
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Research Progress on Epigenetics of Diabetic Cardiomyopathy in Type 2 Diabetes.
Front Cell Dev Biol2021 ;9():777258. doi: 10.3389/fcell.2021.777258.
Deng Jianxin, Liao Yunxiu, Liu Jianpin, Liu Wenjuan, Yan Dewen,
Abstract
Diabetic cardiomyopathy (DCM) is characterized by diastolic relaxation abnormalities in its initial stages and by clinical heart failure (HF) without dyslipidemia, hypertension, and coronary artery disease in its last stages. DCM contributes to the high mortality and morbidity rates observed in diabetic populations. Diabetes is a polygenic, heritable, and complex condition that is exacerbated by environmental factors. Recent studies have demonstrated that epigenetics directly or indirectly contribute to pathogenesis. While epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs, have been recognized as key players in the pathogenesis of DCM, some of their impacts remain not well understood. Furthering our understanding of the roles played by epigenetics in DCM will provide novel avenues for DCM therapeutics and prevention strategies.
Copyright © 2021 Deng, Liao, Liu, Liu and Yan.
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Neuraminidase 1 deficiency attenuates cardiac dysfunction, oxidative stress, fibrosis, inflammatory via AMPK-SIRT3 pathway in diabetic cardiomyopathy mice.
Int J Biol Sci2022 ;18(2):826-840. doi: 10.7150/ijbs.65938.
Guo Zhen, Tuo Hu, Tang Nan, Liu Fang-Yuan, Ma Shu-Qing, An Peng, Yang Dan, Wang Min-Yu, Fan Di, Yang Zheng, Tang Qi-Zhu,
Abstract
Diabetic cardiomyopathy (DCM) is associated with oxidative stress and augmented inflammation in the heart. Neuraminidases (NEU) 1 has initially been described as a lysosomal protein which plays a role in the catabolism of glycosylated proteins. We investigated the role of NEU1 in the myocardium in diabetic heart. Streptozotocin (STZ) was injected intraperitoneally to induce diabetes in mice. Neonatal rat ventricular myocytes (NRVMs) were used to verify the effect of shNEU1 . NEU1 is up-regulated in cardiomyocytes under diabetic conditions. NEU1 inhibition alleviated oxidative stress, inflammation and apoptosis, and improved cardiac function in STZ-induced diabetic mice. Furthermore, NEU1 inhibition also attenuated the high glucose-induced increased reactive oxygen species generation, inflammation and, cell death . ShNEU1 activated Sirtuin 3 (SIRT3) signaling pathway, and SIRT3 deficiency blocked shNEU1-mediated cardioprotective effects . More importantly, we found AMPK? was responsible for the elevation of SIRT3 expression via AMPK?-deficiency studies and . Knockdown of LKB1 reversed the effect elicited by shNEU1 . In conclusion, NEU1 inhibition activates AMPK? via LKB1, and subsequently activates sirt3, thereby regulating fibrosis, inflammation, apoptosis and oxidative stress in diabetic myocardial tissue.
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studies of Danzhi Jiangtang capsules against diabetic cardiomyopathy via TLR4/MyD88/NF-?B signaling pathway.
Saudi Pharm J2021 Dec;29(12):1432-1440. doi: 10.1016/j.jsps.2021.11.004.
Shi Hui, Zhou Peng, Ni Ying-Qun, Wang Shu-Shu, Song Rui, Shen An-Lu, Fang Zhao-Hui, Wang Liang,
Abstract
Objectives:
Danzhi Jiangtang capsule (DJC) is widely used for preventing and treating diabetic cardiomyopathy (DCM). However, the underlying mechanisms of the anti-inflammatory and antiapoptotic activities are unclear.
Methods:
In the diabetic cardiomyopathy rat model, cardiac function was measured through echocardiography, histological changes in the myocardium were visualized using HE staining, and cardiomyocyte apoptosis was detected using TUNEL. The serum levels of anti-inflammatory cytokines were detected using ELISA. Finally, TLR4, MyD88, and NF-?B mRNA expressions were analyzed using RT-qPCR. In the experiments, the apoptosis rate of the H9c2 cells was detected using FCM; moreover, TLR4, MyD88 and NF-?B mRNA expressions were measured using RT-qPCR and related protein levels were investigated using Western blotting.
Results:
In vivo, DJC effectively improved cardiac function, alleviated the pathological changes, and reduced the apoptosis rate. Moreover, DJC reduced TNF-?, IL-1?, and IL-6 activities, with significant inhibition of the TLR4, MyD88 and NF-?B p65 mRNA expression. Moreover, , DJC effectively inhibited high-glucose-induced H9c2 apoptosis-an effect similar to that for TAK242. Finally, both the DJC and TAK242 considerably reduced TLR4, MyD88, NF-?B, Bax, and caspase-3 protein expression but increased that of BCL-2.
Conclusions:
DJC prevented the overactivation of the TLR4/MyD88/NF-?B signaling pathway and regulate cardiomyocyte apoptosis against DCM.
© 2021 The Author(s).
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Mechanisms of cardiac dysfunction in diabetic cardiomyopathy: molecular abnormalities and phenotypical variants.
Heart Fail Rev2022 Jan;():. doi: 10.1007/s10741-021-10200-y.
Prandi Francesca Romana, Evangelista Isabella, Sergi Domenico, Palazzuoli Alberto, Romeo Francesco,
Abstract
Diabetic cardiomyopathy (DCM) is a diabetes mellitus-induced pathophysiological condition characterized by cardiac structural, functional, and metabolic changes that can result in heart failure (HF), in the absence of coronary artery disease, hypertension, and valvular heart disease. Metabolic alterations such as hyperglycemia, insulin resistance, hyperinsulinemia, and increased metabolism of free fatty acids result in oxidative stress, inflammation, advanced glycation end products formation, abnormalities in calcium homeostasis, and apoptosis that are responsible for structural remodeling. Cardiac stiffness, hypertrophy, and fibrosis eventually lead to dysfunction and HF with preserved ejection fraction and/or HF with reduced ejection fraction. In this review, we analyzed in detail the cellular and molecular mechanisms and the metabolic pathways involved in the pathophysiology of DCM. Different phenotypes are observed in DCM, and it is not clear yet if the restrictive and the dilated phenotypes are distinct or represent an evolution of the same disease. Phenotypic differences can be observed between T1DM and T2DM DCM, possibly explained by the different myocardial insulin action. Further studies are needed in order to better understand the underlying mechanisms of DCM and to identify appropriate therapeutic targets and novel strategies to prevent and reverse the progression toward heart failure in diabetic patients.
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Exosomal microRNAs: potential targets for the prevention and treatment of diabetic cardiomyopathy.
J Cardiol2022 Jan;():. doi: S0914-5087(21)00376-2.
Zhang Tao, Gao Zhe, Chen Kuihao,
Abstract
Diabetic cardiomyopathy (DCM), a condition in which myocardial dysfunction is caused by diabetes mellitus, has become an epidemic disorder in the world. DCM initially presents as diastolic relaxation dysfunction and will progress to heart failure in the absence of coronary artery disease, valvular disease, and other conventional cardiovascular risk factors such as hypertension and dyslipidemia. However, the underlying molecular mechanisms of DCM are poorly understood. Recent studies reveal that exosomal miRNAs are associated with multiple DCM risk factors and may act as potential therapeutic targets. Therefore, this review summarizes the recent advancements to understand the role of exosomal miRNAs in DCM development and explores potential preventative and therapeutic strategies.
Copyright © 2021. Published by Elsevier Ltd.
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Pyrroloquinoline quinone ameliorates diabetic cardiomyopathy by inhibiting the pyroptosis signaling pathway in C57BL/6 mice and AC16 cells.
Eur J Nutr2022 Jan;():. doi: 10.1007/s00394-021-02768-w.
Qu Xue-Feng, Zhai Bing-Zhong, Hu Wen-Li, Lou Min-Han, Chen Yi-Hao, Liu Yi-Feng, Chen Jian-Guo, Mei Song, You Zhen-Qiang, Liu Zhen, Zhang Li-Jing, Zhang Yong-Hui, Wang Yin,
Abstract
PURPOSE:
Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus and is characterized by myocardial hypertrophy and myocardial fibrosis. Pyrroloquinoline quinone (PQQ), a natural nutrient, exerts strong protection against various myocardial diseases. Pyroptosis, a type of inflammation-related programmed cell death, is vital to the development of DCM. However, the protective effects of PQQ against DCM and the associated mechanisms are not clear. This study aimed to investigate whether PQQ protected against DCM and to determine the underlying molecular mechanism.
METHODS:
Diabetes was induced in mice by intraperitoneal injection of streptozotocin, after which the mice were administered PQQ orally (10, 20, or 40 mg/kg body weight/day) for 12 weeks. AC16 human myocardial cells were divided into the following groups and treated accordingly: control (5.5 mmol/L glucose), high glucose (35 mmol/L glucose), and HG?+?PQQ groups (1 and 10 nmol/L PQQ). Cells were treated for 24 h.
RESULTS:
PQQ reduced myocardial hypertrophy and the area of myocardial fibrosis, which was accompanied by an increase in antioxidant function and a decrease in inflammatory cytokine levels. Moreover, myocardial hypertrophy-(ANP and BNP), myocardial fibrosis-(collagen I and TGF-?1), and pyroptosis-related protein levels decreased in the PQQ treatment groups. Furthermore, PQQ abolished mitochondrial dysfunction and the activation of NF-?B/I?B, and decreased NLRP3 inflammation-mediated pyroptosis in AC16 cells under high-glucose conditions.
CONCLUSION:
PQQ improved DCM in diabetic mice by inhibiting NF-?B/NLRP3 inflammasome-mediated cell pyroptosis. Long-term dietary supplementation with PQQ may be greatly beneficial for the treatment of DCM. Diagram of the underlying mechanism of the effects of PQQ on DCM. PQQ inhibits ROS generation and NF-?B activation, which stimulates activation of the NLRP3 inflammasome and regulates the expression of caspase-1, IL-1?, and IL-18. The up-regulated inflammatory cytokines trigger myocardial hypertrophy and cardiac fibrosis and promote the pathological process of DCM.
© 2021. The Author(s).
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