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Pubblicazioni recenti - diabetic cardiomyopathy
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Global Nature of Incipient Chamber Remodeling and Dysfunction in Diabetic Individuals Living in the Community: Potential Mechanisms.
Circ Cardiovasc Imaging2019 Sep;12(9):e009729. doi: 10.1161/CIRCIMAGING.119.009729.
Xie Eric, Lima João A C,
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Changes in Cardiac Morphology and Function in Individuals With Diabetes Mellitus: The UK Biobank Cardiovascular Magnetic Resonance Substudy.
Circ Cardiovasc Imaging2019 Sep;12(9):e009476. doi: 10.1161/CIRCIMAGING.119.009476.
Jensen Magnus T, Fung Kenneth, Aung Nay, Sanghvi Mihir M, Chadalavada Sucharitha, Paiva Jose M, Khanji Mohammed Y, de Knegt Martina C, Lukaschuk Elena, Lee Aaron M, Barutcu Ahmet, Maclean Edd, Carapella Valentina, Cooper Jackie, Young Alistair, Piechnik Stefan K, Neubauer Stefan, Petersen Steffen E,
Abstract
BACKGROUND:
Diabetes mellitus (DM) is associated with increased risk of cardiovascular disease. Detection of early cardiac changes before manifest disease develops is important. We investigated early alterations in cardiac structure and function associated with DM using cardiovascular magnetic resonance imaging.
METHODS:
Participants from the UK Biobank Cardiovascular Magnetic Resonance Substudy, a community cohort study, without known cardiovascular disease and left ventricular ejection fraction ?50% were included. Multivariable linear regression models were performed. The investigators were blinded to DM status.
RESULTS:
A total of 3984 individuals, 45% men, (mean [SD]) age 61.3 (7.5) years, hereof 143 individuals (3.6%) with DM. There was no difference in left ventricular (LV) ejection fraction (DM versus no DM; coefficient [95% CI]: -0.86% [-1.8 to 0.5]; =0.065), LV mass (-0.13 g/m [-1.6 to 1.3], =0.86), or right ventricular ejection fraction (-0.23% [-1.2 to 0.8], =0.65). However, both LV and right ventricular volumes were significantly smaller in DM, (LV end-diastolic volume/m: -3.46 mL/m [-5.8 to -1.2], =0.003, right ventricular end-diastolic volume/m: -4.2 mL/m [-6.8 to -1.7], =0.001, LV stroke volume/m: -3.0 mL/m [-4.5 to -1.5], <0.001; right ventricular stroke volume/m: -3.8 mL/m [-6.5 to -1.1], =0.005), LV mass/volume: 0.026 (0.01 to 0.04) g/mL, =0.006. Both left atrial and right atrial emptying fraction were lower in DM (right atrial emptying fraction: -6.2% [-10.2 to -2.1], =0.003; left atrial emptying fraction:-3.5% [-6.9 to -0.1], =0.043). LV global circumferential strain was impaired in DM (coefficient [95% CI]: 0.38% [0.01 to 0.7], =0.045).
CONCLUSIONS:
In a low-risk general population without known cardiovascular disease and with preserved LV ejection fraction, DM is associated with early changes in all 4 cardiac chambers. These findings suggest that diabetic cardiomyopathy is not a regional condition of the LV but affects the heart globally.
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Carbonic anhydrase II/sodium-proton exchanger 1 metabolon complex in cardiomyopathy of ob type 2 diabetic mice.
J Mol Cell Cardiol2019 Sep;():. doi: S0022-2828(18)31255-0.
de Giusti Carolina Jaquenod, Blanco Paula G, Lamas Paula A, Velasquez Fernanda Carrizo, Lofeudo Juan M, Portiansky Enrique L, Alvarez Bernardo V,
Abstract
Heart failure is the leading cause of death among diabetic people. Cellular and molecular entities leading to diabetic cardiomyopathy are, however, poorly understood. Coupling of cardiac carbonic anhydrase II (CAII) and Na/H exchanger 1 (NHE1) to form a transport metabolon was analyzed in obese type 2 diabetic mice (ob) and control heterozygous littermates (ob). Echocardiography showed elevated systolic interventricular septum thickness and systolic posterior wall thickness in ob mice at 9 and 16?weeks. ob mice showed increased left ventricular (LV) weight/tibia length ratio and increased cardiomyocyte cross sectional area as compared to controls, indicating cardiac hypertrophy. Immunoblot analysis showed increased CAII expression in LV samples of obvs. ob mice, and augmented Ser phosphorylation on NHE1 in ob hearts. Reciprocal co-immunoprecipitation analysis showed strong association of CAII and NHE1 in LV samples of ob mice. NHE1-dependent rate of intracellular pH (pH) normalization after transient acid loading of isolated cardiomyocytes was higher in ob mice vs. ob. NHE transport activity was also augmented in cultured H9C2 rat cardiomyoblasts treated with high glucose/high palmitate, and it was normalized after CA inhibition. We conclude that the NHE1/CAII metabolon complex is exacerbated in diabetic cardiomyopathy of ob mice, which may lead to perturbation of pH and [Na] and [Ca] handling in these diseased hearts.
Copyright © 2018. Published by Elsevier Ltd.
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Mechanics insights of curcumin in myocardial ischemia: Where are we standing?
Eur J Med Chem2019 Aug;183():111658. doi: S0223-5234(19)30802-5.
Ahmed Salman, Khan Haroon, Mirzaei Hamed,
Abstract
Cardiovascular disorders are known as one of the main health problems which are associated with mortality worldwide. Myocardial ischemia (MI) is improper blood supply to myocardium which leads from serious complications to life-threatening problems like AMI, atherosclerosis, hypertension, cardiac-hypertrophy as well as diabetic associated complications as diabetic atherosclerosis/cardiomyopathy/hypertension. Despite several efforts, the current therapeutic platforms are not related with significant results. Hence, it seems, developing novel therapies are required. In this regard, increasing evidences indicated, curcumin (CRC) acts as cardioprotective agent. Given that CRC and its analogs exert their cardioprotective effects via affecting on a variety of cardiovascular diseases-related mechanisms (i.e., Inflammation, and oxidative stress). Herein, for first time, we have highlighted the protective impacts of CRC against MI. This review might be a steppingstone for further investigation into the clinical implications of the CRC against MI. Furthermore, it pulls in light of a legitimate concern for scientific community, seeking novel techniques and characteristic dynamic biopharmaceuticals for use against myocardial ischemia.
Copyright © 2019 Elsevier Masson SAS. All rights reserved.
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GALLIC ACID IMPROVES OXIDATIVE STRESS AND INFLAMMATION THROUGH REGULATING MICRORNAS EXPRESSIONS IN THE BLOOD OF DIABETIC RATS.
Acta Endocrinol (Buchar);15(2):187-194. doi: 10.4183/aeb.2019.187.
Ramezani Ali Akbari F, Badavi M, Dianat M, Mard S A, Ahangarpour A,
Abstract
Context:
Endothelial dysfunction and diabetic cardiomyopathy are critical complications of diabetes. Gallic acid (GA) plays a significant role in cardiovascular disorders resulted from diabetes. In addition, increased plasma miR-24, miR-126 associated with endothelial dysfunction.
Aim:
The current study was designed to assess the effects of GA on plasma miR-24, miR-126 levels in the diabetic rats.
Animals and Methods:
Adult male Sprague-Dawley rats were divided into three groups (n=8): control (C), diabetic (D) and diabetic group treated with GA (D+G, 25 mg/kg, by gavage) for eight weeks. The blood glucose level, body weight, lipid profile, blood pressure, plasma miR-24 and miR-126 levels, antioxidant and inflammatory biomarkers were measured.
Results:
The plasma levels of miR-24, miR-126, body weight, high-density lipoprotein cholesterol (HDL-c), total anti-oxidant capacity (TAC) and the systolic blood pressure significantly reduced and blood glucose, total cholesterol (TC), triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-c), malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-?) and low-density lipoprotein cholesterol (LDL-c) significantly elevated among the diabetic rats compared with the control group. However, GA restored body weight, blood pressure, TC, TG, VLDL-c, TNF-?, miR-126, blood glucose, HDL-c, MDA, TAC, miR-24 and IL-6 among the GA treated rats compared with the diabetic group.
Conclusion:
GA improves inflammation, oxidative stress and hypotension result from diabetes. These protective effects are probably mediated via increasing plasma miR-24 and miR-126 levels.
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FMK, an Inhibitor of p90RSK, Inhibits High Glucose-Induced TXNIP Expression via Regulation of ChREBP in Pancreatic ? Cells.
Int J Mol Sci2019 Sep;20(18):. doi: E4424.
Han Jung-Hwa, Kim Suji, Kim Sujin, Lee Heejung, Park So-Young, Woo Chang-Hoon,
Abstract
Hyperglycemia is the major characteristic of diabetes mellitus, and a chronically high glucose (HG) level causes ?-cell glucolipotoxicity, which is characterized by lipid accumulation, impaired ?-cell function, and apoptosis. TXNIP (Thioredoxin-interacting protein) is a key mediator of diabetic ?-cell apoptosis and dysfunction in diabetes, and thus, its regulation represents a therapeutic target. Recent studies have reported that p90RSK is implicated in the pathogenesis of diabetic cardiomyopathy and nephropathy. In this study, we used FMK (a p90RSK inhibitor) to determine whether inhibition of p90RSK protects ?-cells from chronic HG-induced TXNIP expression and to investigate the molecular mechanisms underlying the effect of FMK on its expression. In INS-1 pancreatic ?-cells, HG-induced ?-cell dysfunction, apoptosis, and ROS generation were significantly diminished by FMK. In contrast BI-D1870 (another p90RSK inhibitor) did not attenuate HG-induced TXNIP promoter activity or TXNIP expression. In addition, HG-induced nuclear translocation of ChREBP and its transcriptional target molecules were found to be regulated by FMK. These results demonstrate that HG-induced pancreatic ?-cell dysfunction resulting in HG conditions is associated with TXNIP expression, and that FMK is responsible for HG-stimulated TXNIP gene expression by inactivating the regulation of ChREBP in pancreatic ?-cells. Taken together, these findings suggest FMK may protect against HG-induced ?-cell dysfunction and TXNIP expression by ChREBP regulation in pancreatic ?-cells, and that FMK is a potential therapeutic reagent for the drug development of diabetes and its complications.
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The protective effects of grape seed procyanidin B2 against asporin mediates glycated low-density lipoproteins induced-cardiomyocyte apoptosis and fibrosis.
Cell Biol Int2019 Sep;():. doi: 10.1002/cbin.11229.
Li Xiao-Li, Yu Fei, Li Bao-Ying, Fu Chun-Li, Yu Xin, Xu Mei, Cheng Mei, Gao Hai-Qing,
Abstract
The progression of diabetic cardiomyopathy is related with the cardiomyoblast cell dysfunction and apoptosis. Our previous studies showed that asporin was significantly increased in the myocardium of db/db mice through proteomics, and grape seed procyanidin B2 (GSPB2) significantly inhibited the expression of asporin in the heart of db/db mice. We reported here that asporin played a critical role in glycated low-density lipoproteins (gly-LDL) induced-cardiomyocyte apoptosis. We found that gly-LDL upregulated asporin expression. Asporin increased H9C2 cardiomyocytes apoptosis with down-regulation of Bcl-2, up-regulation of transforming growth factor-?1, Bax, collagen III, fibronectin, phosphorylation of smad2 and smad3. Whereas, GSPB2 treatment reversed asporin-induced impairments in H9C2 cardiomyocytes. These results provide evidence for the cardioprotective action of GSPB2 against asporin injury, thus suggest a new target for fighting against diabetic cardiomyopathy. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
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Diabetes and Vascular Disease: is it all about Glycemia?
Curr Pharm Des2019 Aug;():. doi: 10.2174/1381612825666190830181944.
Vecchié Alessandra, Montecucco Fabrizio, Vecchié Federico, Dallegri Franco, Bonaventura Aldo,
Abstract
BACKGROUND:
Diabetes is increasing over time, mainly driven by obesity, aging, and urbanization. Classical macro- and microvascular complications represent the final result of a complex interplay involving atherosclerosis at all stages.
METHODS:
In this review, we aim at focusing on most current updates in the pathophysiology of diabetic vascular disease and discussing on how new therapies might influence the management of these patients at high cardiovascular risk. Diabetes shows an accelerated atherosclerosis with a larger inflammatory cell infiltrate, thus favoring the development of heart failure. 'Diabetic cardiomyopathy' perfectly describes a specific ischemia- and hypertension-independent entity due to diabetes-related metabolic alterations on myocardial function. Moreover, platelets from subjects with diabetes display a typical hyperreactivity explaining the stronger adhesion, activation, and aggregation. Additionally, diabetes provokes an exaggerated stimulation of the endothelium, with an increased release of reactive oxygen species and a reduced release of nitric oxide, both key elements of the endothelial dysfunction. Also, the coagulation cascade and leukocytes can activate contributing to this pro-thrombotic environment. Neutrophils have been recently recognized to play a pivotal role by releasing neutrophil extracellular traps. Finally, microparticles from platelets, neutrophils or monocytes are detrimental effectors on the vessel wall and are involved both in vascular dysfunction and in thrombotic complications.
CONCLUSION:
In light of these findings, the therapeutic management of diabetes needs to be mostly focused on limiting the progression of complications by targeting precise pathophysiological mechanisms rather than to the mere glycemic control, which failed to markedly reduce the risk for macrovascular complications and mortality.
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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Simultaneous inhibition of neprilysin and activation of ACE2 prevented diabetic cardiomyopathy.
Pharmacol Rep2019 May;71(5):958-967. doi: S1734-1140(19)30118-5.
Malek Vajir, Sharma Nisha, Gaikwad Anil Bhanudas,
Abstract
BACKGROUND:
Neprilysin inhibitors (NEPi) are assisting the renin-angiotensin system (RAS) inhibitors in halting diabetic cardiomyopathy (DCM). Away from conventional tactic, a recent report revealed the renoprotective potential of NEPi and angiotensin-converting enzyme (ACE2) activator combination therapy against diabetic nephropathy. However, this combination so far not evaluated against DCM, thus the present investigation aiming the same.
METHODS:
Streptozotocin-induced (55?mg/kg, ip) type 1 diabetic (T1D) male Wistar rats were treated with either monotherapy of thiorphan (0.1?mg/kg/day, po) or diminazene aceturate (5?mg/kg/day, po), or their combination therapy, for four weeks. After hemodynamic measurements, all the rats' heart and plasma were collected for biochemistry, ELISA, histopathology, and immunoblotting.
RESULTS:
Metabolic perturbations and failing cardiac functions associated with diabetes were markedly attenuated by combination therapy. Besides, unfavourable alterations in RAS and natriuretic peptides system (NPS) were corrected by combination therapy. Interestingly, combination therapy significantly increased plasma and heart cGMP levels compared to T1D and monotherapy receiving rats. Moreover, rats receiving combination therapy exhibited significant inhibition of activated NF-?B, TGF-? and apoptotic signalling, and a notable reduction in cardiac fibrosis when compared to T1D rats. Expressions of posttranslational histone modifications markers; H3K4Me2 and its methyltransferases (SET7/9 and RBBP5) were significantly enhanced in T1D hearts, which were significantly reduced by combination therapy.
CONCLUSIONS:
The NEPi and ACE2 activator combination therapy effectively prevented DCM by normalising RAS and NPS activities, increasing cGMP, inhibiting inflammatory, pro-fibrotic and apoptotic signalling, and reversing H3K4Me2 and its methyl transferases expressions.
Copyright © 2019 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.
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Enhanced mTOR complex 1 signaling attenuates diabetic cardiac injury in OVE26 mice.
FASEB J2019 Aug;():fj201901206R. doi: 10.1096/fj.201901206R.
Xu Xianmin, Kobayashi Satoru, Timm Derek, Huang Yuan, Zhao Fengyi, Shou Weinian, Liang Qiangrong,
Abstract
The protein kinase mechanistic target of rapamycin (mTOR) performs diverse cellular functions through 2 distinct multiprotein complexes, mTOR complex (mTORC)1 and 2. Numerous studies using rapamycin, an mTORC1 inhibitor, have implicated a role for mTORC1 in several types of heart disease. People with diabetes are more susceptible to heart failure. mTORC1 activity is increased in the diabetic heart, but its functional significance remains controversial. To investigate the role of mTORC1 in the diabetic heart, we crossed OVE26 type 1 diabetic mice with transgenic mice expressing a constitutively active mTOR (mTORca) or kinase-dead mTOR (mTORkd) in the heart. The expression of mTORca or mTORkd affected only mTORC1 but not mTORC2 activities, with corresponding changes in the activities of autophagy, a cellular degradation pathway negatively regulated by mTORC1. Diabetic cardiac damage in OVE26 mice was dramatically reduced by mTORca but exacerbated by mTORkd expression as assessed by changes in cardiac function, oxidative stress, and myocyte apoptosis. These findings demonstrated that the enhanced mTORC1 signaling in the OVE26 diabetic heart was an adaptive response that limited cardiac dysfunction, suggesting that manipulations that enhance mTORC1 activity may reduce diabetic cardiac injury, in sharp contrast to the results previously obtained with rapamycin.-Xu, X., Kobayashi, S., Timm, D., Huang, Y., Zhao, F., Shou, W., Liang, Q. Enhanced mTOR complex 1 signaling attenuates diabetic cardiac injury in OVE26 mice.
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Exosomes derived from cardiac parasympathetic ganglionic neurons inhibit apoptosis in hyperglycemic cardiomyoblasts.
Mol Cell Biochem2019 Aug;():. doi: 10.1007/s11010-019-03604-w.
Singla Reetish, Garner Kaley H, Samsam Mohtashem, Cheng Zixi, Singla Dinender K,
Abstract
Diabetic cardiomyopathy is known to involve two forms of cardiac cell death: apoptosis and necrosis. However, it remains unknown whether hyperglycemia-induced apoptosis in the H9c2 cell culture system is inhibited by parasympathetic ganglionic neurons (PGN) derived exosomes (exos). We isolated PGN and sympathetic ganglionic neurons (SGN) from the right stellate ganglion in rats, and derived exos from these sources. H9c2 cells were divided into 4 groups: (1) Control, (2) H9c2 + Glucose (100 mmol/L), (3) H9c2 + Glucose + PGN-exos, and (4) H9c2 + Glucose + SGN-exos. We determined cell proliferation and viability with an MTT assay kit, and assessed apoptotic cell death with TUNEL staining and ELISA. Data were further confirmed by analyzing the presence of pro-apoptotic proteins Caspase-3 and Bax, and anti-apoptotic protein Bcl-2. Glucose exposed H9c2 cells significantly reduced cell viability, which was improved by PGN-exos, but not by SGN-exos. Furthermore, increased apoptosis in hyperglycemia in H9c2 cells was confirmed with TUNEL staining and cell death ELISA which demonstrated significantly (p?
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Calcitriol and Punica Granatum Extract Concomitantly Attenuate Cardiomyopathy of Diabetic Mother Rats and Their Neonates via Activation of Raf/MEK/ERK Signalling and Mitigation of Apoptotic Pathways.
Folia Biol (Praha)2019 ;65(2):70-87.
El-Mansi A A, Al-Kahtani M A,
Abstract
We investigated the detrimental effects of diabetes on myocardium of pregestational streptozotocin (STZ)-diabetic mother rats and their neonates via evaluations of oxidative redox, inflammatory and apoptotic pathways, also aiming to characterize whether calcitriol and/or pomegranate peel extract confer myocardial protection in hyperglycaemic dams and their foetuses via modulation of the Raf/MEK/ERK cascade. Sixty Sprague-Dawley female rats were randomized into five groups (N = 12): control, diabetic, diabetic treated with calcitriol and/or pomegranate peel extract (PPE), and mated with non-diabetic healthy males. After confirmation of pregnancy, treatments were kept until gestational day (E-18). Serum and cardiac tissues of mothers and foetuses were collected and processed for biochemical, histopathological, and molecular assessments. We observed that, compared to the control, diabetic mothers showed dramatically increased hyperglycaemia and hyperlipidaemia associated with decreased myocardial functions and disrupted maternal performance. Also, diabetic mothers and their neonates exhibited elevated levels of myocardial injury (troponin I, endothelin 1, creatine kinase-MB, lactate dehydrogenase), with increased pro-inflammatory cytokines (interleukin 1, interleukin 1?, transforming growth factor ?) and oxidative redox. Concurrently, the MAPK pathway was significantly down-regulated with increased myocardial apoptotic activity. Furthermore, mRNA expression of angiogenic and fibrotic markers was significantly increased. Paradoxically, calcitriol and/or pomegranate peel extract alleviated these diabetic myocardial insults and normalized the aforementioned assayed parameters. Our findings hypothesized that calcitriol and/or pomegranate peel extract exerted cardioameliorative impacts due to their unique anti-oxidative and anti-inflammatory properties, and thus may be a promising treatment that directly targets the secondary myocardial complications of diabetes in dams and their offspring.
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Enhanced cardiac expression of two isoforms of matrix metalloproteinase-2 in experimental diabetes mellitus.
PLoS One2019 ;14(8):e0221798. doi: 10.1371/journal.pone.0221798.
Lee Hye Won, Lee Sun Ju, Lee Min Young, Park Mi Wha, Kim Sang Sik, Shin Nari, Lovett David H, Bae Sun Sik, Ahn Jinhee, Park Jin-Sup, Oh Jun-Hyok, Choi Jung Hyun, Lee Han Cheol, Cha Kwang Soo, Hong Taek Jong, Song Sang Heon,
Abstract
BACKGROUND:
Diabetic cardiomyopathy (DM CMP) is defined as cardiomyocyte damage and ventricular dysfunction directly associated with diabetes independent of concomitant coronary artery disease or hypertension. Matrix metalloproteinases (MMPs), especially MMP-2, have been reported to underlie the pathogenesis of DM CMP by increasing extracellular collagen content.
PURPOSE:
We hypothesized that two discrete MMP-2 isoforms (full length MMP-2, FL-MMP-2; N-terminal truncated MMP-2, NTT-MMP-2) are induced by high glucose stimulation in vitro and in an experimental diabetic heart model.
METHODS:
Rat cardiomyoblasts (H9C2 cells) were examined to determine whether high glucose can induce the expression of the two isoforms of MMP-2. For the in vivo study, we used the streptozotocin-induced DM mouse heart model and age-matched controls. The changes of each MMP-2 isoform expression in the diabetic mice hearts were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical stains were conducted to identify the location and patterns of MMP-2 isoform expression. Echocardiography was performed to compare and analyze the changes in cardiac function induced by diabetes.
RESULTS:
Quantitative RT-PCR and immunofluorescence staining showed that the two MMP-2 isoforms were strongly induced by high glucose stimulation in H9C2 cells. Although no definite histologic features of diabetic cardiomyopathy were observed in diabetic mice hearts, left ventricular systolic dysfunction was determined by echocardiography. Quantitative RT-PCR and IHC staining showed this abnormal cardiac function was accompanied with the increases in the mRNA levels of the two isoforms of MMP-2 and related to intracellular localization.
CONCLUSION:
Two isoforms of MMP-2 were induced by high glucose stimulation in vitro and in a Type 1 DM mouse heart model. Further study is required to examine the role of these isoforms in DM CMP.
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Diabetic cardiomyopathy: acute and reversible left ventricular systolic dysfunction due to cardiotoxicity of hyperglycaemic hyperosmolar state-a case report?.
Eur Heart J Case Rep2019 Jun;3(2):. doi: ytz049.
Kocaba? Umut, Y?lmaz Özgür, Kurto?lu Volkan,
Abstract
BACKGROUND:
Diabetic cardiomyopathy (DC) is defined as a ventricular diastolic and/or systolic dysfunction, which is directly related to diabetes mellitus (DM) in the absence of coronary artery disease, valvular, congenital or hypertensive heart disease, and alcoholism. In this report, we present an unusual case of a patient with DC and reversible, acute left ventricular systolic dysfunction due to cardiotoxicity of hyperosmolar hyperglycaemic state (HHS).
CASE SUMMARY:
A 20-year-old male patient presented with weakness and polyuria. Physical examination and electrocardiogram were normal. Laboratory results and arterial blood gas analysis were consistent with HHS. Baseline echocardiography showed global left ventricular hypokinesis with an ejection fraction (EF) of 36%. The patient's clinical condition improved after blood glucose level normalization and echocardiography revealed progressive improvement in the left ventricular systolic function with an EF of 54% at the 5-day follow-up and an EF of 69% at the 15-day follow-up.
DISCUSSION:
Uncontrolled DM and hyperglycaemic crisis may result in cardiotoxicity, acute left ventricular systolic dysfunction, and DC. The pathophysiological mechanism of this phenomenon is still unclear. Blood glucose control is the most important strategy for the prevention of DC.
© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.
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Immunometabolic cross-talk in the inflamed heart.
Cell Stress2019 Jun;3(8):240-266. doi: 10.15698/cst2019.08.194.
Marelli-Berg Federica M, Aksentijevic Dunja,
Abstract
Inflammatory processes underlie many diseases associated with injury of the heart muscle, including conditions without an obvious inflammatory pathogenic component such as hypertensive and diabetic cardiomyopathy. Persistence of cardiac inflammation can cause irreversible structural and functional deficits. Some are induced by direct damage of the heart muscle by cellular and soluble mediators but also by metabolic adaptations sustained by the inflammatory microenvironment. It is well established that both cardiomyocytes and immune cells undergo metabolic reprogramming in the site of inflammation, which allow them to deal with decreased availability of nutrients and oxygen. However, like in cancer, competition for nutrients and increased production of signalling metabolites such as lactate initiate a metabolic cross-talk between immune cells and cardiomyocytes which, we propose, might tip the balance between resolution of the inflammation versus adverse cardiac remodeling. Here we review our current understanding of the metabolic reprogramming of both heart tissue and immune cells during inflammation, and we discuss potential key mechanisms by which these metabolic responses intersect and influence each other and ultimately define the prognosis of the inflammatory process in the heart.
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Role of CCR2 in the Development of Streptozotocin-treated Diabetic Cardiomyopathy.
Diabetes2019 Aug;():. doi: db181231.
Tan Xin, Hu Lizhi, Shu Zhiping, Chen Long, Li Xiangrao, Du Meng, Sun Dan, Mao Xiaoxiang, Deng Shan, Huang Kai, Zhang Fengxiao,
Abstract
CCR2 has been proved to play an important role in diabetes. However, the role of CCR2 in diabetic cardiomyopathy has not been examined. In this study, we investigated the effects of cardiac CCR2 on diabetic cardiomyopathy. We created streptozotocin (STZ)-induced diabetic cardiomyopathy model. Expression of CCR2 were up-regulated in STZ-induced diabetic hearts. CCR2 knockout (CCR2 KO) significantly improved STZ-induced cardiac dysfunction and fibrosis. Moreover, deletion of CCR2 inhibited the STZ induced the apoptosis as well as the production of STZ-induced reactive oxygen species (ROS) in the heart. CCR2 knockout resulted in M2 polarization in heart from STZ treated-mice. Meantime, CCR2 inhibitor treatment also reversed hyperglycemia induced cardiac dysfunction in db/db mice. Our results suggested that cardiac CCR2-induced inflammation and oxidative stress are involved in the development of diabetic cardiomyopathy and CCR2 could be a novel target for therapy.
© 2019 by the American Diabetes Association.
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Association of Diabetes Mellitus on Cardiac Remodeling, Quality of Life, and Clinical Outcomes in Heart Failure With Reduced and Preserved Ejection Fraction.
J Am Heart Assoc2019 Sep;8(17):e013114. doi: 10.1161/JAHA.119.013114.
Yap Jonathan, Tay Wan Ting, Teng Tiew-Hwa Katherine, Anand Inder, Richards A Mark, Ling Lieng Hsi, MacDonald Michael R, Chandramouli Chanchal, Tromp Jasper, Siswanto Bambang B, , Zile Michael, McMurray John, Lam Carolyn S P,
Abstract
Background Diabetes mellitus frequently coexists with heart failure (HF), but few studies have compared the associations between diabetes mellitus and cardiac remodeling, quality of life, and clinical outcomes, according to HF phenotype. Methods and Results We compared echocardiographic parameters, quality of life (assessed by the Kansas City Cardiomyopathy Questionnaire), and outcomes (1-year all-cause mortality, cardiovascular mortality, and HF hospitalization) between HF patients with and without type 2 diabetes mellitus in the prospective ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) Registry, as well as community-based controls without HF. Adjusted Cox proportional hazards models were used to assess the association of diabetes mellitus with clinical outcomes. Among 5028 patients with HF and reduced ejection fraction (HFrEF; EF <40%) and 1139 patients with HF and preserved EF (HFpEF; EF ?50%), the prevalences of type 2 diabetes mellitus were 40.2% and 45.0%, respectively (P=0.003). In both HFrEF and HFpEF cohorts, diabetes mellitus (versus no diabetes mellitus) was associated with smaller indexed left ventricular diastolic volumes and higher mitral E/e' ratio. There was a predominance of eccentric hypertrophy in HFrEF and concentric hypertrophy in HFpEF. Patients with diabetes mellitus had lower Kansas City Cardiomyopathy Questionnaire scores in both HFpEF and HFrEF, with more prominent differences in HFpEF (P<0.05). In both HFpEF and HFrEF, patients with diabetes mellitus had more HF rehospitalizations (adjusted hazard ratio, 1.27; 95% CI, 1.05-1.54; P=0.014) and higher 1-year rates of the composite of all-cause mortality/HF hospitalization (adjusted hazard ratio, 1.22; 95% CI, 1.05-1.41; P=0.011), with no differences between HF phenotypes (P>0.05). Conclusions In HFpEF and HFrEF, type 2 diabetes mellitus is associated with smaller left ventricular volumes, higher mitral E/e' ratio, poorer quality of life, and worse outcomes, with several differences noted between HF phenotypes. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01633398.
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Klotho improves diabetic cardiomyopathy by suppressing the NLRP3 inflammasome pathway.
Life Sci2019 Oct;234():116773. doi: S0024-3205(19)30700-3.
Li Xuelian, Li Zhiyang, Li Bingong, Zhu Xianjie, Lai Xingjun,
Abstract
AIMS:
NLRP3 inflammasome activation is essential for the development and prognosis of diabetic cardiomyopathy (DCM). The anti-aging protein Klotho is suggested to modulate tissue inflammatory responses. The aim of the present study was to examine the protective effects of Klotho on DCM.
MAIN METHODS:
A streptozotocin-induced diabetes mouse model was established to assess the effects of Klotho in vivo, which was administered for 12?weeks. The characteristics of type 1 DCM were evaluated by general status, echocardiography, and histopathology. The expression of associated factors was determined by RT-qPCR and western blotting. Parallel experiments to determine the molecular mechanism through which Klotho prevents DCM were performed using H9C2 cells exposed to high glucose (35?mM).
KEY FINDINGS:
Diabetes-induced increases in serum creatine kinase-muscle/brain and lactate dehydrogenase levels, cardiac fibrosis, cardiomyocyte apoptosis, and cardiac dysfunction were ameliorated by Klotho. Additionally, Klotho suppressed TXNIP expression, NLRP3 inflammasome activation, and expression of the inflammatory cytokines tumor necrosis factor ?, interleukin-1?, and interleukin-18 in vivo. In high glucose-cultured cardiomyocytes, Klotho and N-acetylcysteine significantly downregulated intracellular reactive oxygen species generation and TXNIP/NLRP3 inflammasome activation. Pretreatment of H9C2 cells with NLRP3 siRNA or Klotho prevented high glucose-induced inflammation and apoptosis in H9C2 cells.
SIGNIFICANCE:
Our results demonstrate that the protective effect of Klotho on diabetes-induced cardiac injury is associated with inhibition of the NLRP3 inflammasome pathway, suggesting its therapeutic potential for DCM.
Copyright © 2019 Elsevier Inc. All rights reserved.
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The metabolic syndrome in heart failure: insights to specific mechanisms.
Heart Fail Rev2019 Aug;():. doi: 10.1007/s10741-019-09838-6.
Gargiulo Paola, Marsico Fabio, Renga Francesco, Dell'Aversana Simona, Esposito Immacolata, Marciano Caterina, Dellegrottaglie Santo, Perrone-Filardi Pasquale, Paolillo Stefania,
Abstract
The presence of comorbidities significantly influences long-term morbidity and mortality of symptomatic and asymptomatic heart failure (HF) patients. Metabolic syndrome and diabetic cardiomyopathy are two clinical conditions that share multiple pathophysiological mechanisms and that might be both responsible for cardiac dysfunction. However, it is argued whether metabolic syndrome (MS) independently increases HF risk or the association between MS and HF merely reflects the impact of individual risk factors included in its definition on HF development. Similarly, in the context of diabetic cardiomyopathy, many aspects are still challenging starting from the definition up to the therapeutic management. In this clinical review, we focused the attention on molecular pathways, myocyte alterations, and specific patterns of metabolic syndrome and diabetic cardiomyopathy in order to better define the potential diagnostic and therapeutic approaches of these two pathological conditions.
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Minireview: are SGLT2 inhibitors heart savers in diabetes?
Heart Fail Rev2019 Aug;():. doi: 10.1007/s10741-019-09849-3.
Grubi? Rotkvi? Petra, Cigrovski Berkovi? Maja, Bulj Nikola, Rotkvi? Luka,
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a class of drugs that promote urinary glucose excretion in the treatment of diabetes, have provoked large interest of scientific and professional community due to their positive and, somehow, unexpected results in the three major cardiovascular outcome trials (EMPA-REG OUTCOME trial with empagliflozin, CANVAS Program with canagliflozin, and DECLARE-TIMI 58 with dapagliflozin). In fact, along with the reduction of major adverse cardiovascular events, SGLT2 inhibitors reduced significantly hospitalization for heart failure regardless of existing atherosclerotic cardiovascular disease or a history of heart failure. The latter have reminded us of the frequent but neglected entity of diabetic cardiomyopathy which is currently poorly understood despite its great clinical importance. Physiological mechanisms responsible for the benefits of SGLT2 inhibitors are complex and multifactorial and still not well defined. Interestingly, the time frame of their effect excludes a glucose- and antiatherosclerotic-mediated effect. It would be of great importance to better understand SGLT2 inhibitor mechanisms of action since they could have a potential to be used in early stages of diabetes as cardioprotective agents. There are widely available biomarkers as well as echocardiography that are used in everyday clinical practice and could elucidate physiological mechanisms in the heart protection with SGLT2 inhibitors treatment but studies are still lacking. The purpose of this minireview is to summarize the latest concepts about SGLT2 inhibitors and its benefits regarding diabetic cardiomyopathy especially on its early stage development and to discuss controversies and potential future developments in the field.
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