Lipid Metabolite Biomarkers in Cardiovascular Disease: Discovery and Biomechanism Translation from Human Studies

doi:10.3390/metabo11090621

Review

. 2021 Sep 14;11(9):621.

doi: 10.3390/metabo11090621.

Lipid Metabolite Biomarkers in Cardiovascular Disease: Discovery and Biomechanism Translation from Human Studies

Peter McGranaghan^{1

2}, Jennifer A Kirwan^{3

4

5}, Mariel A Garcia-Rivera^{3

4}, Burkert Pieske^{1

6

7

8}, Frank Edelmann^{1

6

8}, Florian Blaschke^{1

6}, Sandeep Appunni⁹, Anshul Saxena², Muni Rubens², Emir Veledar^{2

10

11}, Tobias Daniel Trippel^{1

6}

Affiliations

¹ Department of Internal Medicine and Cardiology, Charité Campus Virchow-Klinikum, 13353 Berlin, Germany.
² Baptist Health South Florida, Miami, FL 33143, USA.
³ Metabolomics Platform, Berlin Institute of Health at Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.
⁴ Max Delbrück Center for Molecular Research, 13125 Berlin, Germany.
⁵ School of Veterinary Medicine and Science, University of Nottingham, Leicestershire LE12 5RD, UK.
⁶ DZHK (German Centre for Cardiovascular Research), 13353 Berlin, Germany.
⁷ Berlin Institute of Health, 13353 Berlin, Germany.
⁸ German Heart Center Berlin, Department of Cardiology, 13353 Berlin, Germany.
⁹ Department of Biochemistry, Government Medical College, Kozhikode, Kerala 673008, India.
¹⁰ Department of Biostatistics, Florida International University, Miami, FL 33199, USA.
¹¹ Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA.

PMID: 34564437
PMCID: PMC8470800
DOI: 10.3390/metabo11090621

Review

Lipid Metabolite Biomarkers in Cardiovascular Disease: Discovery and Biomechanism Translation from Human Studies

Peter McGranaghan et al. Metabolites. 2021.

. 2021 Sep 14;11(9):621.

doi: 10.3390/metabo11090621.

Authors

Affiliations

¹ Department of Internal Medicine and Cardiology, Charité Campus Virchow-Klinikum, 13353 Berlin, Germany.
² Baptist Health South Florida, Miami, FL 33143, USA.
³ Metabolomics Platform, Berlin Institute of Health at Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.
⁴ Max Delbrück Center for Molecular Research, 13125 Berlin, Germany.
⁵ School of Veterinary Medicine and Science, University of Nottingham, Leicestershire LE12 5RD, UK.
⁶ DZHK (German Centre for Cardiovascular Research), 13353 Berlin, Germany.
⁷ Berlin Institute of Health, 13353 Berlin, Germany.
⁸ German Heart Center Berlin, Department of Cardiology, 13353 Berlin, Germany.
⁹ Department of Biochemistry, Government Medical College, Kozhikode, Kerala 673008, India.
¹⁰ Department of Biostatistics, Florida International University, Miami, FL 33199, USA.
¹¹ Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA.

PMID: 34564437
PMCID: PMC8470800
DOI: 10.3390/metabo11090621

Abstract

Lipids represent a valuable target for metabolomic studies since altered lipid metabolism is known to drive the pathological changes in cardiovascular disease (CVD). Metabolomic technologies give us the ability to measure thousands of metabolites providing us with a metabolic fingerprint of individual patients. Metabolomic studies in humans have supported previous findings into the pathomechanisms of CVD, namely atherosclerosis, apoptosis, inflammation, oxidative stress, and insulin resistance. The most widely studied classes of lipid metabolite biomarkers in CVD are phospholipids, sphingolipids/ceramides, glycolipids, cholesterol esters, fatty acids, and acylcarnitines. Technological advancements have enabled novel strategies to discover individual biomarkers or panels that may aid in the diagnosis and prognosis of CVD, with sphingolipids/ceramides as the most promising class of biomarkers thus far. In this review, application of metabolomic profiling for biomarker discovery to aid in the diagnosis and prognosis of CVD as well as metabolic abnormalities in CVD will be discussed with particular emphasis on lipid metabolites.

Keywords: biomarkers; cardiovascular disease; heart failure; lipidomics; metabolomics.

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Conflict of interest statement

The authors declare no conflict of interest. J.A.K. has been an invited Biocrates speaker in the past (travel expenses only) and is an external consultant for Centogene GmBH.

Figures

**Figure 1**
Overview of the -omic hieararchy and contributing factors to an individual’s phenotype.

**Figure 2**
General metabolomic approach for biomarker analysis.

See this image and copyright information in PMC

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References

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1. Ahmad T., Kelly J.P., McGarrah R.W., Hellkamp A.S., Fiuzat M., Testani J.M., Wang T.S., Verma A., Samsky M.D., Donahue M.P., et al. Prognostic Implications of Long-Chain Acylcarnitines in Heart Failure and Reversibility With Mechanical Circulatory Support. J. Am. Coll. Cardiol. 2016;67:291–299. doi: 10.1016/j.jacc.2015.10.079. - DOI - PMC - PubMed
1. Alshehry Z.H., Mundra P.A., Barlow C.K., Mellett N.A., Wong G., McConville M.J., Simes J., Tonkin A.M., Sullivan D.R., Barnes E.H., et al. Plasma Lipidomic Profiles Improve on Traditional Risk Factors for the Prediction of Cardiovascular Events in Type 2 Diabetes Mellitus. Circulation. 2016;134:1637–1650. doi: 10.1161/CIRCULATIONAHA.116.023233. - DOI - PubMed

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[1] Virani S.S., Alonso A., Benjamin E.J., Bittencourt M.S., Callaway C.W., Carson A.P., Chamberlain A.M., Chang A.R., Cheng S., Delling F.N., et al. Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation. 2020;141:e139–e596. doi: 10.1161/CIR.0000000000000757. - DOI - PubMed

[2] Virani S.S., Alonso A., Benjamin E.J., Bittencourt M.S., Callaway C.W., Carson A.P., Chamberlain A.M., Chang A.R., Cheng S., Delling F.N., et al. Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation. 2020;141:e139–e596. doi: 10.1161/CIR.0000000000000757. - DOI - PubMed

[3] Neubauer S. The failing heart—An engine out of fuel. N. Engl. J. Med. 2007;356:1140–1151. doi: 10.1056/NEJMra063052. - DOI - PubMed

[4] Neubauer S. The failing heart—An engine out of fuel. N. Engl. J. Med. 2007;356:1140–1151. doi: 10.1056/NEJMra063052. - DOI - PubMed

[5] Karwi Q.G., Uddin G.M., Ho K.L., Lopaschuk G.D. Loss of Metabolic Flexibility in the Failing Heart. Front. Cardiovasc. Med. 2018;5:68. doi: 10.3389/fcvm.2018.00068. - DOI - PMC - PubMed

[6] Karwi Q.G., Uddin G.M., Ho K.L., Lopaschuk G.D. Loss of Metabolic Flexibility in the Failing Heart. Front. Cardiovasc. Med. 2018;5:68. doi: 10.3389/fcvm.2018.00068. - DOI - PMC - PubMed

[7] Ahmad T., Kelly J.P., McGarrah R.W., Hellkamp A.S., Fiuzat M., Testani J.M., Wang T.S., Verma A., Samsky M.D., Donahue M.P., et al. Prognostic Implications of Long-Chain Acylcarnitines in Heart Failure and Reversibility With Mechanical Circulatory Support. J. Am. Coll. Cardiol. 2016;67:291–299. doi: 10.1016/j.jacc.2015.10.079. - DOI - PMC - PubMed

[8] Ahmad T., Kelly J.P., McGarrah R.W., Hellkamp A.S., Fiuzat M., Testani J.M., Wang T.S., Verma A., Samsky M.D., Donahue M.P., et al. Prognostic Implications of Long-Chain Acylcarnitines in Heart Failure and Reversibility With Mechanical Circulatory Support. J. Am. Coll. Cardiol. 2016;67:291–299. doi: 10.1016/j.jacc.2015.10.079. - DOI - PMC - PubMed

[9] Alshehry Z.H., Mundra P.A., Barlow C.K., Mellett N.A., Wong G., McConville M.J., Simes J., Tonkin A.M., Sullivan D.R., Barnes E.H., et al. Plasma Lipidomic Profiles Improve on Traditional Risk Factors for the Prediction of Cardiovascular Events in Type 2 Diabetes Mellitus. Circulation. 2016;134:1637–1650. doi: 10.1161/CIRCULATIONAHA.116.023233. - DOI - PubMed

[10] Alshehry Z.H., Mundra P.A., Barlow C.K., Mellett N.A., Wong G., McConville M.J., Simes J., Tonkin A.M., Sullivan D.R., Barnes E.H., et al. Plasma Lipidomic Profiles Improve on Traditional Risk Factors for the Prediction of Cardiovascular Events in Type 2 Diabetes Mellitus. Circulation. 2016;134:1637–1650. doi: 10.1161/CIRCULATIONAHA.116.023233. - DOI - PubMed

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Lipid Metabolite Biomarkers in Cardiovascular Disease: Discovery and Biomechanism Translation from Human Studies

Affiliations

Lipid Metabolite Biomarkers in Cardiovascular Disease: Discovery and Biomechanism Translation from Human Studies

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Affiliations

Abstract

Conflict of interest statement

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Abstract

Conflict of interest statement

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