Apoptotic and non-apoptotic programmed cardiomyocyte death in ventricular remodelling

Dorn, II Gerald W.

doi:10.1093/cvr/cvn243

Cited by 266 publications

(205 citation statements)

References 119 publications

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“…The rate of CM apoptosis in patients with diabetes is 85‐fold greater than that in nondiabetics (Ho, Liu, Liau, Huang & Lin‐Shiau, 2000). Diabetes‐induced CM apoptosis has been associated with excessive generation of reactive free radicals even though other inductive pathways exist as well (Dorn, 2009; Robertson et al., 2004). Increased ROS production and reduced antioxidant levels in diabetes have been widely documented in previous reports (Fiordaliso et al., 2004; Houstis et al., 2006).…”

Section: Discussionmentioning

confidence: 99%

Glucagon‐like peptide‐1 ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via the PPARα pathway

Wang

et al. 2018

Aging Cell

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SummaryLipotoxicity cardiomyopathy is the result of excessive accumulation and oxidation of toxic lipids in the heart. It is a major threat to patients with diabetes. Glucagon‐like peptide‐1 (GLP‐1) has aroused considerable interest as a novel therapeutic target for diabetes mellitus because it stimulates insulin secretion. Here, we investigated the effects and mechanisms of the GLP‐1 analog exendin‐4 and the dipeptidyl peptidase‐4 inhibitor saxagliptin on cardiac lipid metabolism in diabetic mice (DM). The increased myocardial lipid accumulation, oxidative stress, apoptosis, and cardiac remodeling and dysfunction induced in DM by low streptozotocin doses and high‐fat diets were significantly reversed by exendin‐4 and saxagliptin treatments for 8 weeks. We found that exendin‐4 inhibited abnormal activation of the (PPARα)‐CD36 pathway by stimulating protein kinase A (PKA) but suppressing the Rho‐associated protein kinase (ROCK) pathway in DM hearts, palmitic acid (PA)‐treated rat h9c2 cardiomyocytes (CMs), and isolated adult mouse CMs. Cardioprotection in DM mediated by exendin‐4 was abolished by combination therapy with the PPARα agonist wy‐14643 but mimicked by PPARα gene deficiency. Therefore, the PPARα pathway accounted for the effects of exendin‐4. This conclusion was confirmed in cardiac‐restricted overexpression of PPARα mediated by adeno‐associated virus serotype‐9 containing a cardiac troponin T promoter. Our results provide the first direct evidence that GLP‐1 protects cardiac function by inhibiting the ROCK/PPARα pathway, thereby ameliorating lipotoxicity in diabetic cardiomyopathy.

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Section: Discussionmentioning

confidence: 99%

Glucagon‐like peptide‐1 ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via the PPARα pathway

Wang

et al. 2018

Aging Cell

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“…Several studies reported a role for autophagy in programmed cell death type II (nonapoptotic death) in heart disease [15,16] and indicated that excessive autophagy could lead to cell death. Valentim et al [17] showed that inhibition of autophagy, by both genetic and pharmacological inhibition of Beclin 1, reduced cell death in cardiomyocytes subjected to simulated ischemia-reperfusion.…”

Section: Discussionmentioning

confidence: 99%

Salvianolic acid B inhibits autophagy and protects starving cardiac myocytes

Han

Liu

2010

Acta Pharmacol Sin

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Aim: To investigate the protective or lethal role of autophagy and the effects of Salvianolic acid B (Sal B) on autophagy in starving myocytes. Methods: Cardiac myocytes were incubated under starvation conditions (GD) for 0, 1, 2, 3, and 6 h. Autophagic flux in starving cells was measured via chloroquine (3 µmol/L). After myocytes were treated with Sal B (50 µmol/L) in the presence or absence of chloroquine (3 µmol/L) under GD 3 h, the amount of LC3-II, the abundance of LC3-positive fluorescent dots in cells, cell viability and cellular ATP levels were determined using immunoblotting, immunofluorescence microscopy, MTT assay and luminometer, respectively. Moreover, electron microscopy (EM) and immunofluorescent duel labeling of LC3 and Caspase-8 were used to examine the characteristics of autophagy and apoptosis. Results: Immunoblot analysis showed that the amount of LC3-II in starving cells increased in a time-dependent manner accompanied by increased LC3-positive fluorescence and decreased cell viability and ATP content. Sal B (50 µmol/L) inhibited the increase in LC3-II, reduced the abundance of LC3 immunofluorescence and intensity of Caspase-8 fluorescence, and enhanced cellular viability and ATP levels in myocytes under GD 3 h, regardless of whether chloroquine was present. Conclusion: Autophagy induced by starvation for 3 h led to cell injury. Sal B protected starving cells by blocking the early stage of autophagic flux and inhibiting apoptosis that occurred during autophagy.

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“…We and others have demonstrated that calpain-1 is important in cardiomyocyte apoptosis and cardiac proinflammatory responses under pathological conditions (16 -19). Both apoptosis and inflammation contribute to post-MI remodeling (20,21). Thus, calpain may be implicated in myocardial remodeling.…”

Section: Myocardial Infarction (Mi)mentioning

confidence: 99%

Deficiency of Capn4 Gene Inhibits Nuclear Factor-κB (NF-κB) Protein Signaling/Inflammation and Reduces Remodeling after Myocardial Infarction

Wei²,

Wang

et al. 2012

Journal of Biological Chemistry

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Background:The causal role of calpain in myocardial remodeling after infarction has not been addressed. Results: Deficiency of Capn4 inhibited NF-B signaling and inflammation and reduced myocardial remodeling, dysfunction, and mortality after infarction. Conclusion: Calpain contributes to myocardial inflammation and remodeling after infarction. Significance: This study provides a significant insight into the function of calpain in post-myocardial infarction remodeling.

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Apoptotic and non-apoptotic programmed cardiomyocyte death in ventricular remodelling

Cited by 266 publications

References 119 publications

Glucagon‐like peptide‐1 ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via the PPARα pathway

Glucagon‐like peptide‐1 ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via the PPARα pathway

Salvianolic acid B inhibits autophagy and protects starving cardiac myocytes

Deficiency of Capn4 Gene Inhibits Nuclear Factor-κB (NF-κB) Protein Signaling/Inflammation and Reduces Remodeling after Myocardial Infarction

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