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. 2021 May 15;13(5):4224-4232.
eCollection 2021.

Metabolic profile of heart tissue in cyanotic congenital heart disease

Shuo Dong  1 , Liying Wu  2 , Yabing Duan  1 , Hao Cui  1 , Kai Chen  1 , Xiao Chen  1 , Yangxue Sun  1 , Chuhao Du  1 , Jie Ren  1 , Songren Shu  1 , Xin Yan  1 , Xinhong Wan  3 , Jiangping Song  1 , Jun Yan  1
Affiliations

Metabolic profile of heart tissue in cyanotic congenital heart disease

Shuo Dong et al. Am J Transl Res. .

Abstract

Background: Cyanotic congenital heart disease (CCHD) is one of the most common birth anomalies, in which chronic hypoxia is the basic pathophysiological process.

Methods: To investigate the heart's metabolic remodeling to hypoxia, we performed an untargeted metabolomic analysis of cardiac tissue from 20 CCHD patients and 15 patients with acyanotic congenital heart disease (ACHD).

Results: A total of 71 (63%) metabolites from 113 detected substances in cardiac tissue differed between the CCHD and ACHD groups. A partial least squares discriminant analysis showed separation between the CCHD and ACHD groups. A pathway enrichment analysis revealed that the most enriched metabolic pathways were amino acid metabolism and energy metabolism. Eleven amino acids were increased in CCHD patients, indicating that protein synthesis was down-regulated. Most of the metabolites in Krebs circle were increased in CCHD patients, suggesting down regulation of aerobic energy metabolism. Hierarchical cluster analysis showed that nicotinamide adenine dinucleotide (NAD) was clustered with Krebs cycle related substrates and its level was significantly higher in CCHD than that in ACHD patients. These analyses suggest that NAD might play an important role in response to hypoxia in CCHD patients.

Conclusion: Our data showed a significantly different metabolic profile in CCHD patients compared to ACHD patients, including reduced protein synthesis and aerobic energy production, and the increased level of NAD in the myocardium may be a response mechanism to hypoxia.

Keywords: Congenital heart disease; Krebs cycle; chronic hypoxia; metabolomics; nicotinamide adenine dinucleotide.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Metabolites distribution and directional changes in heart tissue. A. Class distribution of differential identified metabolites. B. Percentage of metabolites that increased, decreased and unchanged in each class.
Figure 2
Figure 2
Partial Least Squares Discriminant Analysis (PLS-DA) of cardiac tissue metabolites.
Figure 3
Figure 3
Pathway impact analysis of metabolic changes.
Figure 4
Figure 4
The difference of amino acids involved in protein synthesis.
Figure 5
Figure 5
Changed metabolites involved in Krebs circle. *The metabolites without bar graph were not detected.
Figure 6
Figure 6
Hierarchal cluster analysis of the patients with CHD based on their metabolic profile.
Figure 7
Figure 7
The relative quantification of NAD in myocardium from CCHD and ACHD. ***P < 0.001.
See this image and copyright information in PMC

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References

    1. van der Linde D, Konings EE, Slager MA, Witsenburg M, Helbing WA, Takkenberg JJ, Roos-Hesselink JW. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;58:2241–7. - PubMed
    1. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39:1890–900. - PubMed
    1. Bernier PL, Stefanescu A, Samoukovic G, Tchervenkov CI. The challenge of congenital heart disease worldwide: epidemiologic and demographic facts. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2010;13:26–34. - PubMed
    1. Jorgensen M, McPherson E, Zaleski C, Shivaram P, Cold C. Stillbirth: the heart of the matter. Am J Med Genet A. 2014;164A:691–9. - PubMed
    1. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012;125:e2–e220. - PMC - PubMed

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