PPAR Gamma Expression Levels during Development of Heart Failure in Patients with Coronary Artery Disease after Coronary Artery Bypass-Grafting

Wojtkowska, Izabela; Tysarowski, Andrzej; Seliga, Katarzyna; Siedlecki, Janusz A.; Juraszyński, Zbigniew; Marona, Miłosz; Greszata, Lidia; Skrobisz, Anna; Kamiński, Karol; Sawicki, Robert; Stępińska, Janina

doi:10.1155/2014/242790

Cited by 6 publications

(7 citation statements)

References 24 publications

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“…PPAR‐γ has mostly been considered as a crucial metabolic sensor connected with glucose and lipid metabolism homeostasis, lipid storage, and adipogenesis (Lehrke & Lazar, ; Lim, ). PPAR‐γ may attenuate plaque stabilization by reducing matrix metallopeptidase 9 (MMP‐9) expression and promote the formation of foam cell by stimulating the intake of oxidized LDL (Kersten, Desvergne, Desvergne, & Wahli, ) which may also be offset by PPAR‐γ–dependent or independent counter‐regulatory mechanisms (Chrisman et al, ; Wojtkowska et al, ). All of these suggest that PPAR‐γ can link altered lipid and glucose metabolism with CAD development especially in DM.…”

Section: Discussionmentioning

confidence: 99%

Circulating miR‐130 and its target PPAR‐γ may be potential biomarkers in patients of coronary artery disease with type 2 diabetes mellitus

Yuan

Peng

Liu

et al. 2019

Molec Gen & Gen Med

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Background Patients of coronary artery disease (CAD) with type 2 diabetes mellitus (DM2) show increased mortality risk than CAD patients without DM2, while few biomarkers can be used to discriminate them. Methods Fifty‐nine patients of CAD with DM2 (DM2‐CAD group), 79 patients of CAD without DM2 (CAD group), and 63 healthy control subjects were recruited. Circulating miR‐130 (miR‐130a and miR‐130b) and PPAR‐γ (peroxisome proliferator‐activated receptor gamma) were measured and their Pearson correlation was analyzed. 3′ UTR binding prediction and luciferase assay were used to determine the target relationship between miR‐130 and PPAR‐γ. Receiver operating characteristics (ROC) analysis was performed to test the discrimination ability of miR‐130 between DM2‐CAD and CAD groups. Results miR‐130a and miR‐130b showed decreased expression in DM2‐CAD group when compared with the CAD group and health control. Both bioinformatics and luciferase assays showed that miR‐130 could bind the 3′ UTR of PPAR‐γ. Furthermore, miR‐130 negatively correlated with PPAR‐γ in both CAD and DM2‐CAD group in Pearson's coefficient analysis. Both miR‐130a and miR‐130b were able to discriminate DM2‐CAD group from CAD group and control subjects. Conclusion Circulating miR‐130 may regulate the expression of PPAR‐γ and can be used as a biomarker to discriminate DM2‐CAD from CAD.

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Section: Discussionmentioning

confidence: 99%

Circulating miR‐130 and its target PPAR‐γ may be potential biomarkers in patients of coronary artery disease with type 2 diabetes mellitus

Yuan

Peng

Liu

et al. 2019

Molec Gen & Gen Med

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“…The level of PPAR γ in the myocardium was not able to predict development of heart failure after CABG, as was shown in our previous work [18]. However, in the group of patients, in whom heart failure develops during the follow-up, higher myocardial PPAR γ level seems to preserve the systolic function of the left ventricle.…”

Section: Discussionmentioning

confidence: 53%

“…In the HF group one patient died because of myocardial infarction in 1 year after CABG. The baseline characteristics of the study group were presented in the previous paper [18]. One month after CABG 106 patients (67%) were diagnosed with heart failure based on NT-proBNP exceeding 400 pg/mL or LVEF < 40%.…”

Section: Resultsmentioning

confidence: 99%

“…Samples of the left ventricular myocardium were harvested during the CABG procedure, and tissue fragments were placed in the “RNA later” solution (Qiagen) immediately after surgery and stored until RNA isolation. Expression of PPAR γ mRNA was determined in these samples by means of quantitative real-time PCR using TaqMan probes as previously described [18]. …”

Section: Methodsmentioning

confidence: 99%

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Myocardial Expression of PPARγand Exercise Capacity in Patients after Coronary Artery Bypass Surgery

et al. 2017

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Activation of PPARs may be involved in the development of heart failure (HF). We evaluated the relationship between expression of PPARγ in the myocardium during coronary artery bypass grafting (CABG) and exercise tolerance initially and during follow-up. 6-minute walking test was performed before CABG, after 1, 12, 24 months. Patients were divided into two groups (HF and non-HF) based on left ventricular ejection fraction and plasma proBNP level. After CABG, 67% of patients developed HF. The mean distance 1 month after CABG in HF was 397 ± 85 m versus 420 ± 93 m in non-HF. PPARγ mRNA expression was similar in both HF and non-HF groups. 6MWT distance 1 month after CABG was inversely correlated with PPARγ level only in HF group. Higher PPARγ expression was related to smaller LVEF change between 1 month and 1 year (R = 0.18, p < 0.05), especially in patients with HF. Higher initial levels of IL-6 in HF patients were correlated with longer distance in 6MWT one month after surgery and lower PPARγ expression. PPARγ expression is not related to LVEF before CABG and higher PPARγ expression in the myocardium of patients who are developing HF following CABG may have some protecting effect.

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“…Wojtkowska et al. ( 2014 ) observed that PPARγ expression level is considerably upregulated during development of heart failure in patients with coronary artery disease after coronary artery bypass-grafting. Accumulated evidence suggested that the production of tumour necrosis factor α (TNFα) by cardiac myocytes promotes the development and progression of heart failure, and PPARγ agonists can potently inhibit the cardiac expression of TNFα through attenuating NF-κB activation, suggesting that treatment with the agonists may prevent the development of congestive heart failure (Takano et al.…”

Section: Introductionmentioning

confidence: 99%

Rational screening of peroxisome proliferator-activated receptor-γ agonists from natural products: potential therapeutics for heart failure

Chen

Wan

Song

et al. 2016

Pharmaceutical Biology

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Context: Peroxisome proliferator-activated receptor-γ (PPARγ) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Activation of PPARγ pathway has been shown to enhance fatty acid oxidation, improve endothelial cell function, and decrease myocardial fibrosis in heart failure. Thus, the protein has been raised as an attractive target for heart failure therapy.Objective: This work attempted to discover new and potent PPARγ agonists from natural products using a synthetic strategy of computer virtual screening and transactivation reporter assay.Materials and methods: A large library of structurally diverse, drug-like natural products was compiled, from which those with unsatisfactory pharmacokinetic profile and/or structurally redundant compounds were excluded. The binding mode of remaining candidates to PPARγ ligand-binding domain (LBD) was computationally modelled using molecular docking and their relative binding potency was ranked by an empirical scoring scheme. Consequently, eight commercially available hits with top scores were selected and their biological activity was determined using a cell-based reporter-gene assay.Results: Four natural product compounds, namely ZINC13408172, ZINC4292805, ZINC44179 and ZINC901461, were identified to have high or moderate agonistic potency against human PPARγ with EC50 values of 0.084, 2.1, 0.35 and 5.6 μM, respectively, which are comparable to or even better than that of the approved PPARγ full agonists pioglitazone (EC50 = 0.16 μM) and rosiglitazone (EC50 = 0.034 μM). Hydrophobic interactions and van der Waals contacts are the primary chemical forces to stabilize the complex architecture of PPARγ LBD domain with these agonist ligands, while few hydrogen bonds, salt bridges and/or π-π stacking at the complex interfaces confer selectivity and specificity for the domain-agonist recognition.Discussion and conclusion: The integrated in vitro-in silico screening strategy can be successfully applied to rational discovery of biologically active compounds. The newly identified natural products with PPARγ agonistic potency are considered as promising lead scaffolds to develop novel chemical therapeutics for heart failure.

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PPAR Gamma Expression Levels during Development of Heart Failure in Patients with Coronary Artery Disease after Coronary Artery Bypass-Grafting

Cited by 6 publications

References 24 publications

Circulating miR‐130 and its target PPAR‐γ may be potential biomarkers in patients of coronary artery disease with type 2 diabetes mellitus

Circulating miR‐130 and its target PPAR‐γ may be potential biomarkers in patients of coronary artery disease with type 2 diabetes mellitus

Myocardial Expression of PPARγand Exercise Capacity in Patients after Coronary Artery Bypass Surgery

Rational screening of peroxisome proliferator-activated receptor-γ agonists from natural products: potential therapeutics for heart failure

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