Sphingomyelins of Local Fat Depots and Blood Serum as Promising Biomarkers of Cardiovascular Diseases
Assessment of the blood lipid spectrum does not always properly reflect local dysfunctional changes in the adipose tissue and prevents identification of all patients at high risk of cardiovascular diseases (CVD). Monitoring of changes in sphingomyelin levels allows to assess and anticipate the development and/or severity of these diseases, as well as to make sphingomyelins new therapeutic targets.
The aim of the study was to evaluate the sphingomyelin spectrum of local fat depots and blood serum in connection with clinical and instrumental indicators in patients with coronary artery disease (CAD) and patients with degenerative acquired valvular heart disease (AVHD).
Materials and Methods. The study analyzed samples of subcutaneous, epicardial, perivascular adipose tissue (SAT, EAT, PVAT, respectively) received from 30 patients with CAD and 30 patients with AVHD. Sphingomyelin spectrum of the blood serum was assessed using a high-resolution chromatography-mass spectrometric complex (liquid chromatograph of the Agilent 1200 series (Agilent Technologies, USA) with a maXis impact mass spectrometric detector (Bruker Daltonics, Germany)). Determination of the levels of sphingomyelins (SM) in adipose tissue samples was conducted by high performance liquid chromatography with mass spectrometric detection in the mass/charge ratio range from 100 to 1700.
Results. Consistent sphingomyelin spectrum of local fat depots and blood serum was revealed in CAD and AVHD. However, the content of SM varied: in CAD, a specific enhancement of SM in epicardial adipose tissue was observed compared to subcutaneous and perivascular localization. In AVHD, PVAT was characterized by a statistically significant increase in the levels of all SM relative to EAT. Almost all measured SM types in the serum of patients with CAD were higher than the levels in the AVHD group.
Conclusion. Established associations of indicators of the sphingomyelin profile of adipose tissue and blood serum with clinical and instrumental indicators in CVD indicate the relationship between the metabolism of SM in adipose tissue of cardiac localization and disorders of systolic and diastolic function of the LV in patients with CVD, multivessel coronary disease in CAD and allow the use of SM as promising biomarkers of CVD. However, further research is needed to clarify the nature of these relationships.
- Noothi S.K., Ahmed M.R., Agrawal D.K. Residual risks and evolving atherosclerotic plaques. Mol Cell Biochem 2023; 478(12): 2629–2643, https://doi.org/10.1007/s11010-023-04689-0.
- Barchuk M., Dutour A., Ancel P., Svilar L., Miksztowicz V., Lopez G., Rubio M., Schreier L., Nogueira J.P., Valéro R., Béliard S., Martin J.C., Berg G., Gaborit B. Untargeted lipidomics reveals a specific enrichment in plasmalogens in epicardial adipose tissue and a specific signature in coronary artery disease. Arterioscler Thromb Vasc Biol 2020; 40(4): 986–1000, https://doi.org/10.1161/atvbaha.120.313955.
- Brel N.K., Gruzdeva O.V., Kokov A.N., Masenko V.L., Belik E.V., Dyleva Yu.A., Tarasov R.S., Kuzmina A.A., Kashtalap V.V., Barbarash O.L. Relationship of coronary calcinosis and local fat deposts in patients with coronary artery disease. Kompleksnye problemy serdecno-sosudistyh zabolevanij 2022; 11(3): 51–63, https://doi.org/10.17802/2306-1278-2022-11-3-51-63.
- Carreira A.C., Santos T.C., Lone M.A., Zupančič E., Lloyd-Evans E., de Almeida R.F.M., Hornemann T., Silva L.C. Mammalian sphingoid bases: biophysical, physiological and pathological properties. Prog Lipid Res 2019; 75: 100988, https://doi.org/10.1016/j.plipres.2019.100988.
- Taniguchi M., Okazaki T. The role of sphingomyelin and sphingomyelin synthases in cell death, proliferation and migration-from cell and animal models to human disorders. Biochim Biophys Acta 2014; 1841(5): 692–703, https://doi.org/10.1016/j.bbalip.2013.12.003.
- Torretta E., Barbacini P., Al-Daghri N.M., Gelfi C. Sphingolipids in obesity and correlated co-morbidities: the contribution of gender, age and environment. Int J Mol Sci 2019; 20(23): 5901, https://doi.org/10.3390/ijms20235901.
- Hammad S.M., Pierce J.S., Soodavar F., Smith K.J., Al Gadban M.M., Rembiesa B., Klein R.L., Hannun Y.A., Bielawski J., Bielawska A. Blood sphingolipidomics in healthy humans: impact of sample collection methodology. J Lipid Res 2010; 51(10): 3074–3087, https://doi.org/10.1194/jlr.d008532.
- Hanamatsu H., Ohnishi S., Sakai S., Yuyama K., Mitsutake S., Takeda H., Hashino S., Igarashi Y. Altered levels of serum sphingomyelin and ceramide containing distinct acyl chains in young obese adults. Nutr Diabetes 2014; 4(10): e141, https://doi.org/10.1038/nutd.2014.38.
- Jiang X.C., Paultre F., Pearson T.A., Reed R.G., Francis C.K., Lin M., Berglund L., Tall A.R. Plasma sphingomyelin level as a risk factor for coronary artery disease. Arterioscler Thromb Vasc Biol 2000; 20(12): 2614–2618, https://doi.org/10.1161/01.atv.20.12.2614.
- Poss A.M., Maschek J.A., Cox J.E., Hauner B.J., Hopkins P.N., Hunt S.C., Holland W.L., Summers S.A., Playdon M.C. Machine learning reveals serum sphingolipids as cholesterol-independent biomarkers of coronary artery disease. J Clin Invest 2020; 130(3): 1363–1376, https://doi.org/10.1172/jci131838.
- Sigruener A., Kleber M.E., Heimerl S., Liebisch G., Schmitz G., Maerz W. Glycerophospholipid and sphingolipid species and mortality: the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. PLoS One 2014; 9(1): e85724, https://doi.org/10.1371/journal.pone.0085724.
- Tomášová P., Čermáková M., Pelantová H., Vecka M., Kratochvílová H., Lipš M., Lindner J., Ivák P., Netuka I., Šedivá B., Haluzík M., Kuzma M. Lipid profiling in epicardial and subcutaneous adipose tissue of patients with coronary artery disease. J Proteome Res 2020; 19(10): 3993–4003, https://doi.org/10.1021/acs.jproteome.0c00269.
- Kolak M., Westerbacka J., Velagapudi V.R., Wågsäter D., Yetukuri L., Makkonen J., Rissanen A., Häkkinen A.M., Lindell M., Bergholm R., Hamsten A., Eriksson P., Fisher R.M., Oresic M., Yki-Järvinen H. Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity. Diabetes 2007; 56(8): 1960–1968, https://doi.org/10.2337/db07-0111.
- Edsfeldt A., Dunér P., Ståhlman M., Mollet I.G., Asciutto G., Grufman H., Nitulescu M., Persson A.F., Fisher R.M., Melander O., Orho-Melander M., Borén J., Nilsson J., Gonçalves I. Sphingolipids contribute to human atherosclerotic plaque inflammation. Arter Thromb Vasc Biol 2016; 36(6): 1132–1140, https://doi.org/10.1161/atvbaha.116.305675.
- Song J.H., Kim G.T., Park K.H., Park W.J., Park T.S. Bioactive sphingolipids as major regulators of coronary artery disease. Biomol Ther (Seoul) 2021; 29(4): 373–383, https://doi.org/10.4062/biomolther.2020.218.
- Li Z., Chiang Y.P., He M., Zhang K., Zheng J., Wu W., Cai J., Chen Y., Chen G., Chen Y., Dong J., Worgall T.S., Jiang X.C. Effect of liver total sphingomyelin synthase deficiency on plasma lipid metabolism. Biochim Biophys Acta Mol Cell Biol Lipids 2021; 1866(5): 158898, https://doi.org/10.1016/j.bbalip.2021.158898.
- Lehti S., Käkelä R., Hörkkö S., Kummu O., Helske-Suihko S., Kupari M., Werkkala K., Kovanen P.T., Oörni K. Modified lipoprotein-derived lipid particles accumulate in human stenotic aortic valves. PLoS One 2013; 8(6): e65810, https://doi.org/10.1371/journal.pone.0065810.
- Doppler C., Arnhard K., Dumfarth J., Heinz K., Messner B., Stern C., Koal T., Klavins K., Danzl K., Pitterl F., Grimm M., Oberacher H., Bernhard D. Metabolomic profiling of ascending thoracic aortic aneurysms and dissections — implications for pathophysiology and biomarker discovery. PLoS One 2017; 12(5): e0176727, https://doi.org/10.1371/journal.pone.0176727.
