Preliminary evidence for the presence of multiple forms of cell death in diabetes cardiomyopathy

Wei, Jinjing; Zhao, Yongting; Liang, Haihai; Du, Weijie; Wang, Lihong

doi:10.1016/j.apsb.2021.08.026

Cited by 57 publications

(38 citation statements)

References 186 publications

(287 reference statements)

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“…DCM is diagnosed by detecting both structural and functional alterations in the left ventricle (LV) ( 19 ). Using M-mode echocardiography, we assessed the protective effect of exogenous SNO on the cardiac function of DCM mice.…”

Section: Resultsmentioning

confidence: 99%

Myocardial protection of S-nitroso-L-cysteine in diabetic cardiomyopathy mice

et al. 2022

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Diabetic cardiomyopathy (DCM) is a severe complication of diabetes mellitus that is characterized by aberrant myocardial structure and function and is the primary cause of heart failure and death in diabetic patients. Endothelial dysfunction plays an essential role in diabetes and is associated with an increased risk of cardiovascular events, but its role in DCM is unclear. Previously, we showed that S-nitroso-L-cysteine(CSNO), an endogenous S-nitrosothiol derived from eNOS, inhibited the activity of protein tyrosine phosphatase 1B (PTP1B), a critical negative modulator of insulin signaling. In this study, we reported that CSNO treatment induced cellular insulin-dependent and insulin-independent glucose uptake. In addition, CSNO activated insulin signaling pathway and promoted GLUT4 membrane translocation. CSNO protected cardiomyocytes against high glucose-induced injury by ameliorating excessive autophagy activation, mitochondrial impairment and oxidative stress. Furthermore, nebulized CSNO improved cardiac function and myocardial fibrosis in diabetic mice. These results suggested a potential site for endothelial modulation of insulin sensitivity and energy metabolism in the development of DCM. Data from these studies will not only help us understand the mechanisms of DCM, but also provide new therapeutic options for treatment.

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Section: Resultsmentioning

confidence: 99%

Myocardial protection of S-nitroso-L-cysteine in diabetic cardiomyopathy mice

et al. 2022

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“…Increased cardiac apoptosis is considered a major risk factor for the development of DCM ( 23 ); we, thus, explored the effects of rice wine functional components on cell apoptosis in DCM mice. In the in vitro experiments, the Bax/Bcl-2 ratio and levels of apoptosis-related proteins, such as Bax and p53, were increased in the HG group but were decreased in both the HG + RWPH group and the HG + RWPE group ( Figures 4A – D ).…”

Section: Resultsmentioning

confidence: 99%

Functional components of Chinese rice wine can ameliorate diabetic cardiomyopathy through the modulation of autophagy, apoptosis, gut microbiota, and metabolites

Yang

Song

Zhou

et al. 2022

Front. Cardiovasc. Med.

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BackgroundDietary polyphenols, polypeptides, and oligosaccharides modulate inflammation and immunity by altering the composition of gut microbiota. The polyphenols and polypeptides in Chinese rice wine have protective effects against cardiovascular disease. In this study, we hypothesized that the polyphenols, polypeptides, and oligosaccharides in Chinese rice wine can ameliorate diabetic cardiomyopathy (DCM) by altering gut microbiota and metabolites.MethodsMice with DCM and high glucose cells were treated with rice wine polyphenols (RWPH), rice wine polypeptides (RWPE), and rice wine oligosaccharides. Cardiac function was evaluated by echocardiography and detection of myocardial injury markers. We observed the pathological structures using hematoxylin and eosin staining, Masson's trichrome staining, and transmission electron microscopy. The expression levels of autophagy-related proteins and stubRFP-sensGFP-LC3 fluorescence were measured to evaluate autophagy. We performed TUNEL staining and measured the levels of Bax, Bcl-2, and p53 to assess apoptosis. To analyze the effects of the rice wine functional components on the gut microbiota and metabolites of DCM mice, we performed fecal 16S-rDNA gene sequencing and serum untargeted metabolomics.ResultsOur results showed an increase in cardiac and mitochondrial function, promotion of autophagy, and inhibition of cardiomyocyte apoptosis, which indicates that RWPH and RWPE can ameliorate DCM. The abundance of Akkermansia and Desulfovibrio were reduced by the presence of RWPH and RWPE. The growth of the Lachnospiraceae_NK4A136_group and Clostridiales-unclassified were promoted by the presence of RWPH. Tryptophan metabolism-associated metabolites were increased and phenylalanine levels were reduced by the presence of RWPH and RWPE. The biosynthesis of primary bile acids was enhanced by the presence of RWPH.ConclusionBoth RWPH and RWPE provided a protective effect against DCM by promoting autophagy, inhibiting apoptosis, and reversing both gut microbiota dysbiosis and metabolic dysregulation.

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“…The involvement of various forms of cardiomyocyte cell death, such as apoptosis, necroptosis and pyroptosis in I/R injury has been traditionally recognized. 39 , 40 For instances, autophagy was found to be induced at 8 days post LAD-ligation, 41 while apoptosis occurred at 4 weeks post LAD-ligation. 42 Necrosis tends to occur in the reperfusion phase of I/R.…”

Section: Discussionmentioning

confidence: 99%

ALOX15-launched PUFA-phospholipids peroxidation increases the susceptibility of ferroptosis in ischemia-induced myocardial damage

Liu

et al. 2022

Sig Transduct Target Ther

108

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Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to various forms of cell death. It is believed that irreversible myocardial damage resulted from I/R occurs due to oxidative stress evoked during the reperfusion phase. Here we demonstrate that ischemia triggers a specific redox reaction of polyunsaturated fatty acids (PUFA)-phospholipids in myocardial cells, which acts as a priming signaling that initiates the outbreak of robust oxidative damage in the reperfusion phase. Using animal and in vitro models, the crucial lipid species in I/R injury were identified to be oxidized PUFAs enriched phosphatidylethanolamines. Using multi-omics, arachidonic acid 15-lipoxygenase-1 (ALOX15) was identified as the primary mediator of ischemia-provoked phospholipid peroxidation, which was further confirmed using chemogenetic approaches. Collectively, our results reveal that ALOX15 induction in the ischemia phase acts as a “burning point” to ignite phospholipid oxidization into ferroptotic signals. This finding characterizes a novel molecular mechanism for myocardial ischemia injury and offers a potential therapeutic target for early intervention of I/R injury.

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Preliminary evidence for the presence of multiple forms of cell death in diabetes cardiomyopathy

Cited by 57 publications

References 186 publications

Myocardial protection of S-nitroso-L-cysteine in diabetic cardiomyopathy mice

Myocardial protection of S-nitroso-L-cysteine in diabetic cardiomyopathy mice

Functional components of Chinese rice wine can ameliorate diabetic cardiomyopathy through the modulation of autophagy, apoptosis, gut microbiota, and metabolites

ALOX15-launched PUFA-phospholipids peroxidation increases the susceptibility of ferroptosis in ischemia-induced myocardial damage

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