The protective effects of grape seed procyanidin B2 against asporin mediates glycated low‐density lipoprotein induced‐cardiomyocyte apoptosis and fibrosis

Li, Xiaoli; Yu, Fei; Li, Baoying; Fu, Chen; Yu, Xin; Xu, Man; Cheng, Mei; Gao, Haiqing

doi:10.1002/cbin.11229

Cited by 20 publications

(18 citation statements)

References 41 publications

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“… 30 It has been demonstrated that ASPN in the myocardium of the db/db mice was significantly higher than that in the control mice. 31 Thus, ASPN could play an essential role in pathological cardiac remodeling. The findings suggest that LUM and ASPN may contribute to the fibrinogenesis of cardiac remodeling of ICM.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis and Identification of Genes and Pathways in Ischemic Cardiomyopathy

Cao¹,

Liu²,

Liu³

et al. 2021

IJGM

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Purpose Ischemic cardiomyopathy (ICM) is considered to be the most common cause of heart failure, with high prevalence and mortality. This study aimed to investigate the different expressed genes (DEGs) and pathways in the pathogenesis of ICM using bioinformatics analysis. Methods The control and ICM datasets GSE116250, GSE46224 and GSE5406 were collected from the gene expression omnibus (GEO) database. DEGs were identified using limma package of R software, and co-expressed genes were identified using Venn diagrams. Then, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore the biological functions and signaling pathways. Protein–protein interaction (PPI) networks were assembled with Cytoscape software to identify hub genes related to the pathogenesis of ICM. RT-PCR of Heart tissues (n=2 for non-failing controls and n=4 for ischemic cardiomyopathy patients) was used to validate the bioinformatic results. Results A total of 844 DEGs were screened from GSE116250, of which 447 were up-regulated genes and 397 were down-regulated genes, respectively. A total of 99 DEGs were singled out from GSE46224, of which 58 were up-regulated genes and 41 were down-regulated genes, respectively. Thirty DEGs were screened from GSE5406, including 10 genes with up-regulated expression and 20 genes with down-regulated expression. Five up-regulated and 3 down-regulated co-expressed DEGs were intersected in three datasets. GO and KEGG pathway analyses revealed that DEGs are mainly enriched in collagen fibril organization, protein digestion and absorption, AGE-RAGE signaling pathway and other related pathways. Collagen alpha-1(III) chain (COL3A1), collagen alpha-2(I) chain (COL1A2) and lumican (LUM) are the three hub genes in all three datasets through PPI network analysis. The expression of 5 DEGs (SERPINA3, FCN3, COL3A1, HBB, MXRA5) in heart tissues by qRT-PCR results was consistent with our GEO analysis, while expression of 3 DEGs (ASPN, LUM, COL1A2) was opposite with GEO analysis. Conclusion These findings from this bioinformatics network analysis investigated key hub genes, which contributed to better understanding the mechanism and new therapeutic targets of ICM.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis and Identification of Genes and Pathways in Ischemic Cardiomyopathy

Cao¹,

Liu²,

Liu³

et al. 2021

IJGM

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“…ASPN, rstly identi ed as an extracellular secreted protein in 2001, is distinct from other class 1 SLRP family members because of its unique aspartate residues named the D-repeat (30). It has been demonstrated that ASPN in the myocardium of the db/db mice was signi cantly higher than that in the control mice (31). Thus, ASPN could play an important role in pathological cardiac remodeling.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis and Identification of Genes and Pathways in Ischemic Cardiomyopathy

Cao

Liu

et al. 2021

Preprint

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BackgroundIschemic cardiomyopathy (ICM) is considered to be the common cause of heart failure, which has high prevalence and mortality. This study aimed to investigate the different expressed genes (DEGs) and pathways in the pathogenesis of ICM using bioinformatics analysis.MethodsThe control and ICM datasets GSE116250，GSE46224 and GSE5406 were collected from the gene expression omnibus (GEO) database. DEGs were identified using limma package of R software and co-expressed genes were identified with Venn diagrams. Then, the gene otology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explored the biological functions and signaling pathways. Protein-protein interaction (PPI) networks were assembled with Cytoscape software to identify hub genes related to the pathogenesis of ICM.ResultsA total of 844 DEGs were screened from GSE116250, of which 447 up-regulated and 397 down-regulated genes respectively. A total of 99 DEGs were singled out from GSE46224, of which 58 up-regulated and 41 down-regulated genes respectively. 30 DEGs were screened from GSE5406, including 10 genes with up-regulated expression and 20 genes with down-regulated expression. 5 up-regulated and 3 down-regulated co-expressed DEGs were intersected in three datasets. GO and KEGG pathway analyses revealed that DEGs mainly enriched in collagen fibril organization, protein digestion and absorption, AGE-RAGE signaling pathway and other related pathways. Collagen alpha-1(III) chain (COL3A1), collagen alpha-2(I) chain (COL1A2) and lumican (LUM) are the three hub genes in all three datasets through PPI network analysis. The expression of 5 DEGs (SERPINA3, FCN3, COL3A1, HBB, MXRA5) in heart tissues by qRT-PCR results were consistent with our GEO analysis, while expression of 3 DEGs (ASPN, LUM, COL1A2) were opposite with GEO analysis.ConclusionsThese findings from this bioinformatics network analysis investigated key hub genes, which contributed to better understand the mechanism and new therapeutic targets of ICM.

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“…Recent reports have shown modulatory effects of GSPB2 with high phenolic contents of antioxidant status in diabetes. Our previous studies showed that GSPB2 has protective effects against aortic atherosclerosis, renal and pancreas impairment, and cardiomyopathy in DM (Li et al, 2020;Yin et al, 2015;Yu et al, 2012). Yin et al reported that GSPB2 was beneficial to liver lipid metabolism disorders, potentially by decreasing hepatic lipid synthesis via the AMP-activated protein kinase pathway (Yin et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Dimeric procyanidin B2 is one of the main components of GSPE. Our previous studies have demonstrated the antioxidant, antiapoptotic, and cardiovascular protective effects of grape seed procyanidin B2 (GSPB2) (Li et al., 2020). Moreover, Yin et al reported that GSPB2 has a positive effect on hepatic lipid metabolic disorders by reducing hepatic lipid synthesis in db/db mice (Yin et al., 2017).…”

Section: Introductionmentioning

confidence: 99%

Proteomic analysis of liver mitochondria of db/db mice treated with grape seed procyanidin B2

Yin

et al. 2020

J. Food Biochem.

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Hepatic damage has been recognized as one of the major complications in diabetes mellitus. Our previous studies have verified that grape seed procyanidin B2 (GSPB2) played a protective effect on hepatic damage of diabetes. We used isobaric tag for relative and absolute quantitation proteomics here to identify the alterant mitochondrial protein profile in diabetic liver and to seek the protective targets of GSPB2. Proteomics found that 171 proteins were upregulated or downregulated in the liver mitochondria of diabetic group compared to the control group. Of these proteins, 61 were normalized after GSPB2 treatment. These back-regulated proteins are involved in the process of fatty acid oxidation, tricarboxylic acid cycle, oxidative phosphorylation, oxidative stress, and apoptosis. Some differentially expressed proteins were confirmed by western blotting. Our study might help to better understand the mechanism of mitochondrial dysfunction in diabetic liver damage, and provide novel targets for estimating the protective effects of GSPB2. Practical applications Grape seed procyanidin B2 (GSPB2), a polyphenolic component found in red wine and grapes, has beneficial effects such as antioxidative stress, antiapoptosis, and cardiovascular protection. We used proteomics here to identify the differentially expressed mitochondrial proteins in diabetic liver after GSPB2 treatment and to seek the protective targets of GSPB2. We found that the differentially expressed proteins were involved in carbon metabolism, oxidative phosphorylation, fatty acid metabolism, citrate cycle, oxidative stress, and apoptosis. These proteins may play a key role in diabetic hepatic damage as functional proteins. Targeting these proteins including apply of GSPB2 could potentially lead to an effective treatment in the diabetic hepatic disease.

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The protective effects of grape seed procyanidin B2 against asporin mediates glycated low‐density lipoprotein induced‐cardiomyocyte apoptosis and fibrosis

Cited by 20 publications

References 41 publications

Bioinformatics Analysis and Identification of Genes and Pathways in Ischemic Cardiomyopathy

Bioinformatics Analysis and Identification of Genes and Pathways in Ischemic Cardiomyopathy

Bioinformatics Analysis and Identification of Genes and Pathways in Ischemic Cardiomyopathy

Proteomic analysis of liver mitochondria of db/db mice treated with grape seed procyanidin B2

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