Cardiac Phosphodiesterases Are Differentially Increased in Diabetic Cardiomyopathy

Hanna, Rita; Nour‐Eldine, Wared; Saliba, Youakim; Dagher‐Hamalian, Carole; Hachem, Pia; Abou-Khalil, Pamela; Mika, Delphine; Varin, Audrey; Hayek, Magali Samia El; Pereira, Laëtitia; Farès, Nassim; Vandecasteele, Grégoire; Abi-Gerges, Aniella

doi:10.1016/j.lfs.2021.119857

Cited by 13 publications

(27 citation statements)

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“…In some studies of human failing hearts, no change in PDE3 activity was reported 162,177 , whereas decreased PDE3 activity was found in others 178 . Similarly, in animal models of cardiac hypertrophy or HF, decreased PDE3 activity or PDE3A expression was reported in some studies [178][179][180][181][182][183] and increased activity or expression in others [184][185][186][187] .…”

Section: [H1] Pdes In Cardiac Hypertrophy and Hfmentioning

confidence: 70%

Cyclic nucleotide phosphodiesterases as therapeutic targets in cardiac hypertrophy and heart failure

et al. 2022

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

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Section: [H1] Pdes In Cardiac Hypertrophy and Hfmentioning

confidence: 70%

Cyclic nucleotide phosphodiesterases as therapeutic targets in cardiac hypertrophy and heart failure

et al. 2022

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“…The integration analysis highlighted proteins both positively and negatively associated with specific CpGs, worthy following up in future replication/mechanistic studies. Interestingly of the 261 proteins highlighted in the results, we found proteins positively correlated with CpGs located in genes involved in fatty acid metabolism such as COMMD9 , (involved in LDL regulation) [88]; hypertension ( ARHGAP42) [89]; weight loss and muscle development ( APOBEC1 ) [90]; obesity ( PTPRT and PTPRN2) [91-94], and muscle myogenesis and hyperthrophy ( DACT1, DIO2, RPTOR , and PLEKHM3) [95-99] These proteins were also negatively correlated with CpGs located in genes such as KCNMA1, NOTCH1 , and CAMKK2 which are involved in skeletal muscle regeneration, proliferation and differentiation [100-105], DHRS3, DGKG, LPIN1, WNT5A which have been associated with obesity, metabolic syndrome and lipid regulation [106-108], LRRC2 which is a mediator of mitochondrial and cardiac function [109], and PDE4A which has been associated with diabetes [110; 111]. Based on results of this integration, we suggest that future work studying the relationship between such genes/proteins should be prioritized as this may reveal important mechanisms associated with exercise response across multiple OMIC layers.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation and proteomics integration uncover dose-dependent group and individual responses to exercise in human skeletal muscle

Michaux

Landen

Alvarez-Romero

et al. 2022

Preprint

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Objective: Exercise is a major regulator of muscle metabolism, and health benefits acquired by exercise are a result of molecular shifts occurring across multiple OMIC levels (i.e. epigenome, transcriptome, proteome). Identifying robust targets associated with exercise response, at both group and individual levels, is therefore important to develop health guidelines and targeted health interventions. Methods: Twenty, apparently healthy, moderately trained (VO2 max= 51.0 sd= 10.6 mL/min/kg) males (age range= 18-45yrs) from the Gene SMART (Skeletal Muscle Adaptive Responses to Training) study completed a 12-week High-Intensity Interval Training (HIIT) intervention. Muscle biopsies were collected at baseline and after 4, 8, and 12 weeks of HIIT. High throughput DNA methylation (~850 CpG sites), and proteomic (~3000 proteins) analyses were conducted at all-time points. Mixed-models were applied to estimate group and individual changes, and methylome and proteome integration was conducted using a holistic multilevel approach with the mixOmics package. Results: Significant shifts in the methylome (residual analysis) and proteome profiles were observed after 12 weeks of HIIT. 461 proteins significantly changed over time (at 4, 8, and 12 weeks), whilst only one differentially methylated position (DMP) was changed (adj.p-value <0.05). K-means analysis revealed clear protein clustering exhibiting similar changes over time. Individual responses to training were observed in 101 proteins. Seven proteins had a large effect-sizes >0.5, among them are two novel exercise- related proteins, LYRM7 and EPN1. Integration analysis uncovered bidirectional relationships between the methylome and proteome. Conclusions: We showed a significant influence of HIIT on the epigenome and proteome in human muscle, and uncovered groups of proteins clustering according to similar patterns across the exercise intervention. Individual responses to exercise were observed in the proteome with novel mitochondrial and metabolic proteins consistently changed across individuals. Future work is required to elucidate the role of such proteins in response to exercise as well as to investigate the mechanisms associating genes and proteins in response to exercise.

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“…After two weeks of adaptive feeding, the rats in the control group ( n = 8) were intraperitoneally injected with sodium citrate buffer. The remaining rats were injected with an equal volume of 65 mg/kg STZ dissolved in a 0.1 M sodium citrate buffer (pH 4.5) to induce diabetes [ 17 , 18 ]. Following one week of treatment, blood was collected from the tail vein to measure the blood glucose.…”

Section: Methodsmentioning

confidence: 99%

Fufang Xueshuantong Improves Diabetic Cardiomyopathy by Regulating the Wnt/β-Catenin Pathway

Peng

Liu

et al. 2022

International Journal of Endocrinology

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Diabetic cardiomyopathy (DCM) is one of the main complications of diabetic patients and the major reason for the high prevalence of heart failure in diabetic patients. Fufang Xueshuantong (FXST) is a traditional Chinese medicine formula commonly used in the treatment of diabetic retinopathy and stable angina pectoris. However, the role of FXST in DCM has not yet been clarified. This study was conducted to investigate the effects of FXST on diabetic myocardial lesions and reveal its molecular mechanism. The rats were intraperitoneally injected with 65 mg/kg streptozotocin (STZ) to induce diabetes mellitus (DM). DM rats were given saline or FXST. The rats in the control group were intraperitoneally injected with an equal amount of sodium citrate buffer and gavaged with saline. After 12 weeks, echocardiography, heart weight index (HWI), and myocardial pathological changes were determined. The expression of transforming growth factor-beta1 (TGF-β1), collagen I, and collagen III was examined using immunofluorescence staining and western blot. The expressions of Wnt/β-catenin signaling pathway-related proteins and mRNA were detected by western blot and real-time PCR. The results showed that FXST significantly improved cardiac function, ameliorated histopathological changes, and decreased HWI in the DM rats. FXST significantly inhibited the expression of myocardial TGF-β1, collagen I, and collagen III in DM rats. Furthermore, FXST significantly inhibited the Wnt/β-catenin pathway. Taken together, FXST has a protective effect on DCM, which might be mediated by suppressing the Wnt/β-catenin pathway.

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Cardiac Phosphodiesterases Are Differentially Increased in Diabetic Cardiomyopathy

Cited by 13 publications

References 50 publications

Cyclic nucleotide phosphodiesterases as therapeutic targets in cardiac hypertrophy and heart failure

Cyclic nucleotide phosphodiesterases as therapeutic targets in cardiac hypertrophy and heart failure

DNA methylation and proteomics integration uncover dose-dependent group and individual responses to exercise in human skeletal muscle

Fufang Xueshuantong Improves Diabetic Cardiomyopathy by Regulating the Wnt/β-Catenin Pathway

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