Deciphering the gene expression profile of peroxisome proliferator-activated receptor signaling pathway in the left atria of patients with mitral regurgitation

Chen, Mien Cheng; Chang, Jen-Chieh; Lin, Yu Wen; Pan, Kuo‐Li; Ho, Wan Chun; Liu, Wen Hao; Chang, Tzu Hao; Huang, Yao‐Kuang; Fang, Chih Yuan; Chen, Chien Jen

doi:10.1186/s12967-016-0871-3

Cited by 18 publications

(15 citation statements)

References 26 publications

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“…Furthermore, CPT1, which facilitates the transportation of long chain FA into the mitochondrial matrix [34], was also increased by treatment of QSG. ACADL, ACADM, ACAA2 and SCP2, the critical enzymes for β-oxidation of FA within the mitochondria [26][27][28]35], were all upregulated by QSG treatment, indicating that QSG could promote fatty acid β-oxidation.…”

Section: Qsg Promoted Fa Uptake Transportation Into Mitochondria Andmentioning

confidence: 97%

“…FAT/ CD36 medicates the entry of long-chain FA into cardiac cells [25], and CPT1 is the rate-limiting enzyme for transportation of FA from cytoplasm to mitochondria [9]. ACADL, ACADM, ACAA2 and SCP2 facilitate the metabolism of FA through β-oxidation in mitochondria [26][27][28]. The protein levels of cardiac FAT/CD36, CPT1A, ACADL, ACADM, ACAA2 and SCP2 were all impressively reduced in the model group compared to the sham group (P < 0.05 or P < 0.01, Fig.…”

Section: Effects Of Qsg On Fat/cd36-cpt1-fao Pathway In Hf Rats Aftermentioning

confidence: 99%

“…For instance, FA metabolism related molecules FAT/ CD36, CPT1A, ACADL, ACADM and ACAA2 were all transcriptionally regulated by PPAR-RXRs signaling pathway [27]. There are three subtypes of PPAR, including PPARα, PPARβ and PPARγ.…”

Section: Qsg Activated Pparα-rxrs Pathway To Regulate the Transcriptimentioning

confidence: 99%

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Qishen granules exerts cardioprotective effects on rats with heart failure via regulating fatty acid and glucose metabolism

et al. 2020

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Background: Qishen granules (QSG) has been applied to treat heart failure (HF) for decades. Our previous transcriptomics study has suggested that Qishen granules (QSG) could regulate the pathways of cardiac energy metabolism in HF, but the specific regulatory mechanism has not yet been clarified. This study was to investigate the potential mechanism of QSG in regulating myocardial fatty acid (FA) and glucose metabolism in a rat model of HF. Methods:The model of HF was induced by left anterior descending coronary artery ligation. Cardiac structure and function were assessed by cine magnetic resonance imaging (MRI) and echocardiography. Level of glucose metabolism was non-invasively evaluated by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT). Blood lipid levels were determined by enzymatic analysis. The mitochondrial ultrastructure was observed with a transmission electron microscope. The critical proteins related to FA metabolism, glucose metabolism and mitochondrial function were measured by western blotting. The ANOVA followed by a Fisher's LSD test was used for within-group comparisons.Results: QSG ameliorated cardiac functions and attenuated myocardial remodeling in HF model. The levels of serum TC, TG and LDL-C were significantly reduced by QSG. The proteins mediating FA uptake, transportation into mitochondria and β-oxidation (FAT/CD36, CPT1A, ACADL, ACADM, ACAA2 and SCP2) as well as the upstreaming transcriptional regulators of FA metabolism (PPARα, RXRα, RXRβ and RXRγ) were up-regulated by QSG. As to glucose metabolism, QSG inhibited glycolytic activity by decreasing LDHA, while stimulated glucose oxidation by decreasing PDK4. Furthermore, QSG could facilitate tricarboxylic acid cycle, promote the transportation of ATP from mitochondria to cytoplasm and restore the mitochondrial function by increasing SUCLA2, CKMT2 and PGC-1α and decreasing UCP2 simultaneously.Conclusion: QSG improved myocardial energy metabolism through increasing FA metabolism,inhibiting uncoupling of glycolysis from glucose oxidation. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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Section: Qsg Promoted Fa Uptake Transportation Into Mitochondria Andmentioning

confidence: 97%

Section: Effects Of Qsg On Fat/cd36-cpt1-fao Pathway In Hf Rats Aftermentioning

confidence: 99%

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Qishen granules exerts cardioprotective effects on rats with heart failure via regulating fatty acid and glucose metabolism

et al. 2020

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“…Interestingly, the results for gene ontology and pathway enrichment analyses of the genes, expressed differentially in that study, revealed PPAR signaling in the KEGG pathway [13]. Additionally, expressions of genes linked to the PPAR signaling pathway, especially genes related to fatty acid β-oxidation, in the left atria of MR patients reportedly differs from patients with aortic valve disease and normal controls [14]. Mitral regurgitation patients also have significantly higher lipid expression of atrial myocytes compared to normal controls [14].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, expressions of genes linked to the PPAR signaling pathway, especially genes related to fatty acid β-oxidation, in the left atria of MR patients reportedly differs from patients with aortic valve disease and normal controls [14]. Mitral regurgitation patients also have significantly higher lipid expression of atrial myocytes compared to normal controls [14]. Perturbation of lipid homeostasis due to a fatty acid uptake–utilization mismatch in the heart reportedly leads to the development of lipotoxic cardiomyopathy, an acquired form of cardiomyopathy [12].…”

Section: Introductionmentioning

confidence: 99%

Idi1 and Hmgcs2 Are Affected by Stretch in HL-1 Atrial Myocytes

Fang

Chen

Chang

et al. 2018

IJMS

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Background: Lipid expression is increased in the atrial myocytes of mitral regurgitation (MR) patients. This study aimed to investigate key regulatory genes and mechanisms of atrial lipotoxic myopathy in MR. Methods: The HL-1 atrial myocytes were subjected to uniaxial cyclic stretching for eight hours. Fatty acid metabolism, lipoprotein signaling, and cholesterol metabolism were analyzed by PCR assay (168 genes). Results: The stretched myocytes had significantly larger cell size and higher lipid expression than non-stretched myocytes (all p < 0.001). Fatty acid metabolism, lipoprotein signaling, and cholesterol metabolism in the myocytes were analyzed by PCR assay (168 genes). In comparison with their counterparts in non-stretched myocytes, seven genes in stretched monocytes (Idi1, Olr1, Nr1h4, Fabp2, Prkag3, Slc27a5, Fabp6) revealed differential upregulation with an altered fold change >1.5. Nine genes in stretched monocytes (Apoa4, Hmgcs2, Apol8, Srebf1, Acsm4, Fabp1, Acox2, Acsl6, Gk) revealed differential downregulation with an altered fold change <0.67. Canonical pathway analysis, using Ingenuity Pathway Analysis software, revealed that the only genes in the “superpathway of cholesterol biosynthesis” were Idi1 (upregulated) and Hmgcs2 (downregulated). The fraction of stretched myocytes expressing Nile red was significantly decreased by RNA interference of Idi1 (p < 0.05) and was significantly decreased by plasmid transfection of Hmgcs2 (p = 0.004). Conclusions: The Idi1 and Hmgcs2 genes have regulatory roles in atrial lipotoxic myopathy associated with atrial enlargement.

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Abnormal expression of long non-coding RNAs in myocardial infarction

et al. 2017

Heart Vessels

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Myocardial infarction (MI) is the leading cause of fatality worldwide. Our study aimed to investigate the dysregulated long non-coding RNA (lncRNA) in MI and elucidate the mechanism of it in MI. The lncRNA and mRNA expression profiling of the whole left ventricular tissue of MI mice model (8 mice) and Sham group (8 mice) was obtained based on microarray analysis. Differentially expressed lnRNAs/mRNA (DELs/DEMs) were identified in MI. DELs/DEMs co-expression network construction, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted to predict the biological functions of DEMs. Quantitative real-time polymerase chain reaction (qRT-PCR) was subjected to validate the abnormally expressed DELs in left ventricular tissues of MI mice model. Total of 168 DELs (37 up- and 131 down-regulated) and 126 DEMs (87 up- and 39 down-regulated) were identified in MI compared with Sham group. The co-expression network of candidate DELs and DEMs was constructed, which covered 219 nodes and 1775 edges. The qRT-PCR validation results indicated that ENSMUST00000124047 was significantly down-regulated in MI group and AK166279 was significantly up-regulated in MI group. ENSMUST00000121611 and NR_015515 had the up-regulated tendency in MI group compared with Sham group. The DEMs in MI were significantly enriched in 41 signaling pathways including complement and coagulation cascades, cytokine-cytokine receptor interaction and chemokine signaling pathway. The expression profiling of dysregulated DELs in MI was identified. Our results might provide useful information for exploring the pathogenesis mechanism of MI.

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Deciphering the gene expression profile of peroxisome proliferator-activated receptor signaling pathway in the left atria of patients with mitral regurgitation

Cited by 18 publications

References 26 publications

Qishen granules exerts cardioprotective effects on rats with heart failure via regulating fatty acid and glucose metabolism

Qishen granules exerts cardioprotective effects on rats with heart failure via regulating fatty acid and glucose metabolism

Idi1 and Hmgcs2 Are Affected by Stretch in HL-1 Atrial Myocytes

Abnormal expression of long non-coding RNAs in myocardial infarction

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