Pathophysiology and Treatment of Diabetic Cardiomyopathy and Heart Failure in Patients with Diabetes Mellitus

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3587 - 3587

Published: March 25, 2022

There is a close relationship between diabetes mellitus and heart failure, an independent risk factor for failure. Diabetes failure are linked by not only the complication of ischemic disease, but also metabolic disorders such as glucose toxicity lipotoxicity based on insulin resistance. Cardiac dysfunction in absence coronary artery hypertension, valvular disease called diabetic cardiomyopathy. Diabetes-induced hyperglycemia hyperinsulinemia lead to capillary damage, myocardial fibrosis, hypertrophy with mitochondrial dysfunction. Lipotoxicity extensive fat deposits or lipid droplets observed cardiomyocytes. Furthermore, increased oxidative stress inflammation cause cardiac fibrosis hypertrophy. Treatment sodium cotransporter 2 (SGLT2) inhibitor currently one most effective treatments associated diabetes. However, treatment myocardium has yet been established, establishment needed future. This review provides overview patients clinical practice clinicians.

Language: Английский

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Metrnl ameliorates diabetic cardiomyopathy via inactivation of cGAS/STING signaling dependent on LKB1/AMPK/ULK1-mediated autophagy

Journal of Advanced Research, Journal Year: 2022, Volume and Issue: 51, P. 161 - 179

Published: Nov. 10, 2022

Meteorin-like hormone (Metrnl) is ubiquitously expressed in skeletal muscle, heart, and adipose with beneficial roles obesity, insulin resistance, inflammation. Metrnl found to protect against cardiac hypertrophy doxorubicin-induced cardiotoxicity. However, its role diabetic cardiomyopathy (DCM) undefined.We aimed elucidate the potential of DCM.Gain- andloss-of-function experimentswere utilized determine pathological processes DCM.We that plasma levels, myocardial protein mRNA expressions were significantly downregulated both streptozotocin (STZ)-induced (T1D) mice leptin receptor deficiency (db/db) (T2D) mice. Cardiac-specific overexpression (OE) markedly ameliorated injury dysfunction T1D T2D In sharp contrast, specific deletion heart had opposite phenotypes. parallel, OE ameliorated, whereas downregulation exacerbated high glucose (HG)-elicited hypertrophy, apoptosis oxidative damage primary neonatal rat cardiomyocytes. Antibody-induced blockade eliminated effects benefits vitro vivo. Mechanistically, activated autophagy pathway inhibited cGAS/STING signaling a LKB1/AMPK/ULK1-dependent mechanism Besides, Metrnl-induced ULK1 phosphorylation facilitated dephosphorylation mitochondrial translocation STING where it interacted tumor necrosis factor receptor-associated 2 (TRAF2), scaffold E3 ubiquitin ligase was responsible for ubiquitination degradation STING, rendering cardiomyocytes sensitive activation.Thus, may be an attractive therapeutic target or regimen treating DCM.

Language: Английский

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Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms

Cardiovascular Diabetology, Journal Year: 2023, Volume and Issue: 22(1)

Published: April 13, 2023

Abstract Among the complications of diabetes, cardiovascular events and cardiac insufficiency are considered two most important causes death. Experimental clinical evidence supports effectiveness SGLT2i for improving dysfunction. treatment benefits metabolism, microcirculation, mitochondrial function, fibrosis, oxidative stress, endoplasmic reticulum programmed cell death, autophagy, intestinal flora, which involved in diabetic cardiomyopathy. This review summarizes current knowledge mechanisms Graphical

Language: Английский

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Heart failure in type 2 diabetes: current perspectives on screening, diagnosis and management

Cardiovascular Diabetology, Journal Year: 2021, Volume and Issue: 20(1)

Published: Nov. 6, 2021

Abstract Type 2 diabetes is one of the most relevant risk factors for heart failure, prevalence which increasing worldwide. The aim review to highlight current perspectives pathophysiology failure as it pertains type diabetes. This summarizes proposed mechanistic bases, explaining myocardial damage induced by diabetes-related stressors and other factors, i.e., cardiomyopathy in We complex pathology individuals with diabetes, including relationship chronic kidney disease, metabolic alterations, failure. also discuss criteria used diagnosis gold standard screening tools Currently approved pharmacological therapies primary use treatment-guiding role NT-proBNP are presented. Finally, influence presence well on COVID-19 severity briefly discussed.

Language: Английский

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Biomarkers of Oxidative Stress Tethered to Cardiovascular Diseases

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 15

Published: June 24, 2022

Cardiovascular disease (CVD) is a broad term that incorporated group of conditions affect the blood vessels and heart. CVD foremost cause fatalities around world. Multiple pathophysiological mechanisms are involved in CVD; however, oxidative stress plays vital role generating reactive oxygen species (ROS). Oxidative occurs when concentration oxidants exceeds potency antioxidants within body while producing nitrogen (RNS). ROS generated by disrupts cell signaling, DNA damage, lipids, proteins, thereby resulting inflammation apoptosis. Mitochondria primary source production cells. Increased reduces nitric oxide (NO) bioavailability, which elevates vasoconstriction arteries contributes to development hypertension. has also been linked atherosclerotic plaque. Antioxidants can decrease body; various therapeutic drugs have designed treat damage due CVD. The present review provides detailed narrative generation with focus on biomarker its association We discussed complex relationship between endothelial dysfunction as well stress-induced obesity Finally, we reducing

Language: Английский

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Mitochondrial Dynamics and Mitophagy in Cardiometabolic Disease

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: June 17, 2022

Mitochondria play a key role in cellular metabolism. Mitochondrial dynamics (fusion and fission) mitophagy, are critical to mitochondrial function. Fusion allows organelles share metabolites, proteins, DNA, promoting complementarity between damaged mitochondria. Fission increases the number of mitochondria ensure that they passed on their offspring during mitosis. Mitophagy is process selective removal excess or helps improve energy Cardiometabolic disease characterized by dysfunction, high production reactive oxygen species, increased inflammatory response, low levels ATP. closely related mitophagy. This paper reviewed mechanisms mitophagy (focus MFN1, MFN2, OPA1, DRP1, PINK1 proteins) roles diabetic cardiomyopathy, myocardial infarction, cardiac hypertrophy, heart failure, atherosclerosis, obesity.

Language: Английский

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Distinct Roles of DRP1 in Conventional and Alternative Mitophagy in Obesity Cardiomyopathy

Circulation Research, Journal Year: 2023, Volume and Issue: 133(1), P. 6 - 21

Published: May 26, 2023

Obesity induces cardiomyopathy characterized by hypertrophy and diastolic dysfunction. Whereas mitophagy mediated through an Atg7 (autophagy related 7)-dependent mechanism serves as essential to maintain mitochondrial quality during the initial development of obesity cardiomyopathy, Rab9 (Ras-related protein Rab-9A)-dependent alternative takes over role chronic phase. Although it has been postulated that DRP1 (dynamin-related 1)-mediated fission consequent separation damaged portions mitochondria are for mitophagy, involvement in remains controversial. We investigated whether endogenous is mediating 2 forms high-fat diet (HFD)-induced and, if so, what underlying mechanisms are.

Language: Английский

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Mitophagy and cGAS–STING crosstalk in neuroinflammation

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(8), P. 3327 - 3361

Published: May 13, 2024

Mitophagy, essential for mitochondrial health, selectively degrades damaged mitochondria. It is intricately linked to the cGAS–STING pathway, crucial innate immunity. This pathway responds DNA and associated with cellular stress. Our review explores molecular details regulatory mechanisms of mitophagy pathway. We critically evaluated literature demonstrating how dysfunctional leads neuroinflammatory conditions, primarily through accumulation mitochondria, activating activation prompts production proinflammatory cytokines, exacerbating neuroinflammation. emphasizes interaction between Effective might suppress offering protection against Conversely, impaired may activate potentially leading chronic Additionally, we explored this influences neurodegenerative disorders, suggesting a common mechanism in such diseases. In conclusion, there need additional targeted research unravel complexities mitophagy–cGAS–STING interactions their role neurodegeneration. highlights potential therapies targeting these pathways, which could lead new treatments conditions. synthesis enhances our understanding foundations neuroinflammation opens therapeutic avenues disease research.

Language: Английский

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Hyperglycemia triggers RyR2-dependent alterations of mitochondrial calcium homeostasis in response to cardiac ischemia-reperfusion: Key role of DRP1 activation

Redox Biology, Journal Year: 2024, Volume and Issue: 70, P. 103044 - 103044

Published: Jan. 19, 2024

Hyperglycemia increases the heart sensitivity to ischemia-reperfusion (IR), but underlying cellular mechanisms remain unclear. Mitochondrial dynamics (the processes that govern mitochondrial morphology and their interactions with other organelles, such as reticulum), has emerged a key factor in vulnerability IR. However, it is unknown whether contributes hyperglycemia deleterious effect during We hypothesized (i) higher IR hyperglycemic conditions could be explained by on complex interplay between dynamics, Ca

Language: Английский

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Pathophysiology and Advances in the Therapy of Cardiomyopathy in Patients with Diabetes Mellitus

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 5027 - 5027

Published: May 5, 2024

Diabetes mellitus (DM) is known as the first non-communicable global epidemic. It estimated that 537 million people have DM, but condition has been properly diagnosed in less than half of these patients. Despite numerous preventive measures, number DM cases steadily increasing. The state chronic hyperglycaemia body leads to complications, including diabetic cardiomyopathy (DCM). A pathophysiological mechanisms are behind development and progression cardiomyopathy, increased oxidative stress, inflammation, synthesis advanced glycation products overexpression biosynthetic pathway certain compounds, such hexosamine. There extensive research on treatment DCM, there a therapies can stop this complication. Among compounds used treat DCM antiglycaemic drugs, hypoglycaemic drugs myocardial failure. An important element combating should be kept mind healthy lifestyle—a well-balanced diet physical activity. also group compounds—including coenzyme Q10, antioxidants modulators signalling pathways inflammatory processes, among others—that being researched continuously, their introduction into routine likely result greater control more effective future. This paper summarises latest recommendations for lifestyle pharmacological patients with DM.

Language: Английский

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