Cardioprotective effect of pioglitazone and curcumin against diabetic cardiomyopathy in type 1 diabetes mellitus: impact on CaMKII/NF-κB/TGF-β1 and PPAR-γ signaling pathway

Gbr, Aya A; Baky, Nayira A. Abdel; Mohamed, Eman A.; Zaky, Heba S.

doi:10.1007/s00210-020-01979-y

Cited by 24 publications

(11 citation statements)

References 61 publications

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“…The selective PPARγ agonist rosiglitazone is widely used to treat type 2 diabetes; however, this treatment is associated with an increased risk of MI and CV death [169]. Pioglitazone, another selective PPARγ agonist, was recently demonstrated to ameliorate type 1 DiCM in diabetic Sprague Dawley rats by depressing the Ca +2 /calmodulin-dependent protein kinase II (CaMKII) pathway, correlating with reductions in oxidative stress and cardiac fibrosis [52]. Pioglitazone cardioprotection has also been observed in diabetic mice, revealing an alternative mechanism by which PTEN/AKT/FAK modulation reduces collagen deposition and pathological DiCM hypertrophy [51].…”

Section: Pparγmentioning

confidence: 99%

Untangling the Cooperative Role of Nuclear Receptors in Cardiovascular Physiology and Disease

Paredes¹,

Santos-Clemente²,

Ricote³

2021

IJMS

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The heart is the first organ to acquire its physiological function during development, enabling it to supply the organism with oxygen and nutrients. Given this early commitment, cardiomyocytes were traditionally considered transcriptionally stable cells fully committed to contractile function. However, growing evidence suggests that the maintenance of cardiac function in health and disease depends on transcriptional and epigenetic regulation. Several studies have revealed that the complex transcriptional alterations underlying cardiovascular disease (CVD) manifestations such as myocardial infarction and hypertrophy is mediated by cardiac retinoid X receptors (RXR) and their partners. RXRs are members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors and drive essential biological processes such as ion handling, mitochondrial biogenesis, and glucose and lipid metabolism. RXRs are thus attractive molecular targets for the development of effective pharmacological strategies for CVD treatment and prevention. In this review, we summarize current knowledge of RXR partnership biology in cardiac homeostasis and disease, providing an up-to-date view of the molecular mechanisms and cellular pathways that sustain cardiomyocyte physiology.

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Section: Pparγmentioning

confidence: 99%

Untangling the Cooperative Role of Nuclear Receptors in Cardiovascular Physiology and Disease

Paredes¹,

Santos-Clemente²,

Ricote³

2021

IJMS

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“…Therefore, it is still urgent to further explore the exact molecular mechanisms of the development of T1DM. At present, several genes and signaling pathway are identified; for example vitamin D receptor (VDR) 14 , HLA-B and HLA-A 15 , HLA-DQ 16 , HLA‐DQB1, HLA‐DQA1 and HLA‐DRB1 17 , IDDM2 18 , CaMKII/NF-κB/TGF-β1 and PPAR-γ signaling pathway 19 , Keap1/Nrf2 signaling pathway 20 , HIF-1/VEGF pathway 21 , NLRP3 and NLRP1 inflammasomes signaling pathway 22 and NO/cGMP signaling pathway 23 . Therefore, it is crucial to examine the accurate molecular targets included in occurrence and advancement of T1DM, in order to make a contribution to the diagnosis and treatment of T1DM.…”

Section: Introductionmentioning

confidence: 99%

Identification of candidate biomarkers and pathways associated with type 1 diabetes mellitus using bioinformatics analysis

Pujar¹,

Vastrad²,

Kavatagimath

et al. 2022

Sci Rep

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Type 1 diabetes mellitus (T1DM) is a metabolic disorder for which the underlying molecular mechanisms remain largely unclear. This investigation aimed to elucidate essential candidate genes and pathways in T1DM by integrated bioinformatics analysis. In this study, differentially expressed genes (DEGs) were analyzed using DESeq2 of R package from GSE162689 of the Gene Expression Omnibus (GEO). Gene ontology (GO) enrichment analysis, REACTOME pathway enrichment analysis, and construction and analysis of protein–protein interaction (PPI) network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network, and validation of hub genes were performed. A total of 952 DEGs (477 up regulated and 475 down regulated genes) were identified in T1DM. GO and REACTOME enrichment result results showed that DEGs mainly enriched in multicellular organism development, detection of stimulus, diseases of signal transduction by growth factor receptors and second messengers, and olfactory signaling pathway. The top hub genes such as MYC, EGFR, LNX1, YBX1, HSP90AA1, ESR1, FN1, TK1, ANLN and SMAD9 were screened out as the critical genes among the DEGs from the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network. Receiver operating characteristic curve (ROC) analysis confirmed that these genes were significantly associated with T1DM. In conclusion, the identified DEGs, particularly the hub genes, strengthen the understanding of the advancement and progression of T1DM, and certain genes might be used as candidate target molecules to diagnose, monitor and treat T1DM.

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“…In preclinical studies on diabetic mice, the use of pioglitazone remarkably increased ventricular function, reduced fibrosis and TGF-β protein expression in myocardial tissues, and attenuated myocardial hypertrophy [ 75 ]. Moreover, pioglitazone combined with curcumin reduced oxidative stress and fibrosis in diabetic rats, decreasing lipid peroxidation and TGF-β1 level [ 76 ]. However, the use of these drugs in clinical practice is limited due to their potential to cause weight gain, edema, fractures, and HF.…”

Section: Diabetes Therapy and DCmentioning

confidence: 99%

Glycemic Control and the Heart: The Tale of Diabetic Cardiomyopathy Continues

et al. 2022

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Cardiovascular diseases are the leading cause of death in people with diabetes. Diabetic cardiomyopathy (DC) is an important complication of diabetes and represents a distinct subtype of heart failure that occurs in absence of cardiovascular diseases. Chronic hyperglycemia and hyperinsulinemia along with insulin resistance and inflammatory milieu are the main mechanisms involved in the pathophysiology of DC. Changes in lifestyle favoring healthy dietary patterns and physical activity, combined with more innovative anti-diabetes therapies, are the current treatment strategies to safeguard the cardiovascular system. This review aims at providing an updated comprehensive overview of clinical, pathogenetic, and molecular aspects of DC, with a focus on the effects of anti-hyperglycemic drugs on the prevention of pump dysfunction and consequently on cardiovascular health in type 2 diabetes.

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Cardioprotective effect of pioglitazone and curcumin against diabetic cardiomyopathy in type 1 diabetes mellitus: impact on CaMKII/NF-κB/TGF-β1 and PPAR-γ signaling pathway

Cited by 24 publications

References 61 publications

Untangling the Cooperative Role of Nuclear Receptors in Cardiovascular Physiology and Disease

Untangling the Cooperative Role of Nuclear Receptors in Cardiovascular Physiology and Disease

Identification of candidate biomarkers and pathways associated with type 1 diabetes mellitus using bioinformatics analysis

Glycemic Control and the Heart: The Tale of Diabetic Cardiomyopathy Continues

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