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. 2021 Mar 25:8:629734.
doi: 10.3389/fcvm.2021.629734. eCollection 2021.

Explore the Protective Role of Obesity in the Progression of Myocardial Infarction

Siyuan Zhao  1 , Rongyuan Cao  1 , Shuhua Zhang  1 , Yan Kang  2
Affiliations

Explore the Protective Role of Obesity in the Progression of Myocardial Infarction

Siyuan Zhao et al. Front Cardiovasc Med. .

Abstract

Obesity has been shown as a risk factor to increase the incidence of myocardial infarction (MI). However, obesity has also been linked to the decreased mortality of acute MI with unknown mechanisms. Here, we firstly used large-scale literature data mining to identify obesity downstream targets and MI upstream regulators with polarity, based on which an obesity-MI regulatory network was constructed. Then, a gene set enrichment analysis was conducted to explore the functional profile of the genes involved in the obesity-MI regulatory networks. After that, a mega-analysis using MI RNA expression datasets was conducted to test the expression of obesity-specific genes in MI patients, followed by a shortest-path analysis to explore any potential gene-MI association. Our results suggested that obesity could inhibit 11 MI promoters, including NPPB, NPPA, IRS1, SMAD3, MIR155, ADRB1, AVP, MAPK14, MC3R, ROCK1, and COL3A1, which were mainly involved in blood pressure-related pathways. Our study suggested that obesity could influence MI progression by driving multiple genes associated with blood pressure regulation. Moreover, PTH could be a novel obesity driven gene associated with the pathogenesis of MI, which needs further validation.

Keywords: functional networks; gene set enrichment analysis; mega-analysis; myocardial infarction; obesity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Literature-based data mining results. (A) The Venn diagram of obesity targets and myocardial infarction regulators. (B) Obesity → MI Inhibitive networks constructed by MI promoters.
Figure 2
Figure 2
Functional enrichment analysis for the 11 MI-promoters inhibited by obesity within obesity-MI regulatory network.
Figure 3
Figure 3
Volcano plot of the mega-analysis results on the 472 obesity regulators but not implicated with myocardial infarction.
Figure 4
Figure 4
Expression of gene PTH analysis results. (A) Forest plot of the mega-analysis results of PTH; (B) QQplot of the dataset GSE24591, which includes gene PTH.
Figure 5
Figure 5
Shortest path connecting obesity target PTH and MI.
See this image and copyright information in PMC

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References

    1. Zhu J, Su X, Li G, Chen J, Tang B, Yang Y. The incidence of acute myocardial infarction in relation to overweight and obesity: a meta-analysis. Arch Med Sci. (2014) 10:855–62. 10.5114/aoms.2014.46206 - DOI - PMC - PubMed
    1. Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P, et al. . Obesity and risk of myocardial infarction in 27,00 participants from 52 countries: a case–control study. Lancet. (2005) 366:1640–9. 10.1016/S0140-6736(05)67663-5 - DOI - PubMed
    1. Schargrodsky H, Rozlosnik J, Ciruzzi M, Ruffa R, Paterno C, Ardariz M, et al. . Body weight and nonfatal myocardial infarction in a case-control study from Argentina. Soz Praventivmed. (1994) 39:126–33. 10.1007/BF01299656 - DOI - PubMed
    1. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al. . Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. (2004) 364:937–52. 10.1016/S0140-6736(04)17018-9 - DOI - PubMed
    1. Xu Y, Li H, Wang A, Su Z, Yang G, Luo Y, et al. . Association between the metabolically healthy obese phenotype and the risk of myocardial infarction: results from the Kailuan study. Eur J Endocrinol. (2018) 179:343–52. 10.1530/EJE-18-0356 - DOI - PubMed

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