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Published in: Nutrition & Metabolism 1/2011

Open Access 01-12-2011 | Research

Impact of sphingomyelin levels on coronary heart disease and left ventricular systolic function in humans

Authors: Xueying Chen, Aijun Sun, Yunzeng Zou, Junbo Ge, Jason M Lazar, Xian-Cheng Jiang

Published in: Nutrition & Metabolism | Issue 1/2011

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Abstract

Sphingomyelin (SM) is an abundant phospholipid in cell membranes and in lipoproteins. In human plasma, SM is mainly found in atherogenic lipoproteins; therefore, higher levels of SM may promote atherogenesis. We investigated the relations between plasma SM levels and the presence of angiographic coronary heart disease (CHD) and left ventricular systolic dysfunction. We studied 732 patients referred for coronary angiography. Median SM levels were higher among patients with CHD and in those with LV systolic dysfunction (LVEF<50%) than in patients without CHD or LV dysfunction. SM levels were significantly correlated with fibrinogen levels, diabetes, apoB, and triglyceride levels. On multivariate analyses, higher median SM levels were associated with a higher risk of CHD and lower LV ejection fraction. The pro-atherogenic property of plasma SM might be related to 1) CHD; 2) LV systolic dysfunction; and 3) metabolism of apoB-containing or triglyceride-rich lipoproteins.
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Literature
1.
go back to reference Nilsson A, Duan RD: Absorption and lipoprotein transport of sphingomyelin. J Lipid Res. 2006, 47: 154-171.CrossRef Nilsson A, Duan RD: Absorption and lipoprotein transport of sphingomyelin. J Lipid Res. 2006, 47: 154-171.CrossRef
2.
go back to reference Subbaiah PV, Davidson MH, Ritter MC, Buchanan W, Bagdade JD: Effects of dietary supplementation with marine lipid concentrate on the plasma lipoprotein composition of hypercholesterolemic patients. Atherosclerosis. 1989, 79: 157-166. 10.1016/0021-9150(89)90120-2.CrossRef Subbaiah PV, Davidson MH, Ritter MC, Buchanan W, Bagdade JD: Effects of dietary supplementation with marine lipid concentrate on the plasma lipoprotein composition of hypercholesterolemic patients. Atherosclerosis. 1989, 79: 157-166. 10.1016/0021-9150(89)90120-2.CrossRef
3.
go back to reference Rodriguez JL, Ghiselli GC, Torreggiani D, Sirtori CR: Very low density lipoproteins in normal and cholesterol-fed rabbits: lipid and protein composition and metabolism. Part 1. Chemical composition of very low density lipoproteins in rabbits. Atherosclerosis. 1976, 23: 73-83. 10.1016/0021-9150(76)90119-2.CrossRef Rodriguez JL, Ghiselli GC, Torreggiani D, Sirtori CR: Very low density lipoproteins in normal and cholesterol-fed rabbits: lipid and protein composition and metabolism. Part 1. Chemical composition of very low density lipoproteins in rabbits. Atherosclerosis. 1976, 23: 73-83. 10.1016/0021-9150(76)90119-2.CrossRef
4.
go back to reference Zilversmit DB, Mc CE, Jordan PH, Henly WS, Ackerman RF: The synthesis of phospholipids in human atheromatous lesions. Circulation. 1961, 23: 370-375.CrossRef Zilversmit DB, Mc CE, Jordan PH, Henly WS, Ackerman RF: The synthesis of phospholipids in human atheromatous lesions. Circulation. 1961, 23: 370-375.CrossRef
5.
go back to reference Williams KJ, Tabas I: The response-to-retention hypothesis of early atherogenesis. Arterioscler Thromb Vasc Biol. 1995, 15: 551-561.CrossRef Williams KJ, Tabas I: The response-to-retention hypothesis of early atherogenesis. Arterioscler Thromb Vasc Biol. 1995, 15: 551-561.CrossRef
6.
go back to reference Williams KJ, Tabas I: The response-to-retention hypothesis of atherogenesis reinforced. Curr Opin Lipidol. 1998, 9: 471-474.CrossRef Williams KJ, Tabas I: The response-to-retention hypothesis of atherogenesis reinforced. Curr Opin Lipidol. 1998, 9: 471-474.CrossRef
7.
go back to reference Schissel SL, Tweedie-Hardman J, Rapp JH, Graham G, Williams KJ, Tabas I: Rabbit aorta and human atherosclerotic lesions hydrolyze the sphingomyelin of retained low-density lipoprotein. Proposed role for arterial-wall sphingomyelinase in subendothelial retention and aggregation of atherogenic lipoproteins. J Clin Invest. 1996, 98: 1455-1464. 10.1172/JCI118934.CrossRef Schissel SL, Tweedie-Hardman J, Rapp JH, Graham G, Williams KJ, Tabas I: Rabbit aorta and human atherosclerotic lesions hydrolyze the sphingomyelin of retained low-density lipoprotein. Proposed role for arterial-wall sphingomyelinase in subendothelial retention and aggregation of atherogenic lipoproteins. J Clin Invest. 1996, 98: 1455-1464. 10.1172/JCI118934.CrossRef
8.
go back to reference Devlin CM, Leventhal AR, Kuriakose G, Schuchman EH, Williams KJ, Tabas I: Acid sphingomyelinase promotes lipoprotein retention within early atheromata and accelerates lesion progression. Arterioscler Thromb Vasc Biol. 2008, 28: 1723-1730. 10.1161/ATVBAHA.108.173344.CrossRef Devlin CM, Leventhal AR, Kuriakose G, Schuchman EH, Williams KJ, Tabas I: Acid sphingomyelinase promotes lipoprotein retention within early atheromata and accelerates lesion progression. Arterioscler Thromb Vasc Biol. 2008, 28: 1723-1730. 10.1161/ATVBAHA.108.173344.CrossRef
9.
go back to reference Jeong T, Schissel SL, Tabas I, Pownall HJ, Tall AR, Jiang X: Increased sphingomyelin content of plasma lipoproteins in apolipoprotein E knockout mice reflects combined production and catabolic defects and enhances reactivity with mammalian sphingomyelinase. J Clin Invest. 1998, 101: 905-912. 10.1172/JCI870.CrossRef Jeong T, Schissel SL, Tabas I, Pownall HJ, Tall AR, Jiang X: Increased sphingomyelin content of plasma lipoproteins in apolipoprotein E knockout mice reflects combined production and catabolic defects and enhances reactivity with mammalian sphingomyelinase. J Clin Invest. 1998, 101: 905-912. 10.1172/JCI870.CrossRef
10.
go back to reference Plump AS, Smith JD, Hayek T, Aalto-Setala K, Walsh A, Verstuyft JG, Rubin EM, Breslow JL: Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell. 1992, 71: 343-353. 10.1016/0092-8674(92)90362-G.CrossRef Plump AS, Smith JD, Hayek T, Aalto-Setala K, Walsh A, Verstuyft JG, Rubin EM, Breslow JL: Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell. 1992, 71: 343-353. 10.1016/0092-8674(92)90362-G.CrossRef
11.
go back to reference Hojjati MR, Li Z, Zhou H, Tang S, Huan C, Ooi E, Lu S, Jiang XC: Effect of myriocin on plasma sphingolipid metabolism and atherosclerosis in apoE-deficient mice. J Biol Chem. 2005, 280: 10284-10289. 10.1074/jbc.M412348200.CrossRef Hojjati MR, Li Z, Zhou H, Tang S, Huan C, Ooi E, Lu S, Jiang XC: Effect of myriocin on plasma sphingolipid metabolism and atherosclerosis in apoE-deficient mice. J Biol Chem. 2005, 280: 10284-10289. 10.1074/jbc.M412348200.CrossRef
12.
go back to reference Park TS, Panek RL, Mueller SB, Hanselman JC, Rosebury WS, Robertson AW, Kindt EK, Homan R, Karathanasis SK, Rekhter MD: Inhibition of sphingomyelin synthesis reduces atherogenesis in apolipoprotein E-knockout mice. Circulation. 2004, 110: 3465-3471. 10.1161/01.CIR.0000148370.60535.22.CrossRef Park TS, Panek RL, Mueller SB, Hanselman JC, Rosebury WS, Robertson AW, Kindt EK, Homan R, Karathanasis SK, Rekhter MD: Inhibition of sphingomyelin synthesis reduces atherogenesis in apolipoprotein E-knockout mice. Circulation. 2004, 110: 3465-3471. 10.1161/01.CIR.0000148370.60535.22.CrossRef
13.
go back to reference Jiang XC, Paultre F, Pearson TA, Reed RG, Francis CK, Lin M, Berglund L, Tall AR: Plasma sphingomyelin level as a risk factor for coronary artery disease. Arterioscler Thromb Vasc Biol. 2000, 20: 2614-2618.CrossRef Jiang XC, Paultre F, Pearson TA, Reed RG, Francis CK, Lin M, Berglund L, Tall AR: Plasma sphingomyelin level as a risk factor for coronary artery disease. Arterioscler Thromb Vasc Biol. 2000, 20: 2614-2618.CrossRef
14.
go back to reference Schlitt A, Blankenberg S, Yan D, von Gizycki H, Buerke M, Werdan K, Bickel C, Lackner KJ, Meyer J, Rupprecht HJ, Jiang XC: Further evaluation of plasma sphingomyelin levels as a risk factor for coronary artery disease. Nutr Metab (Lond). 2006, 3: 5-10.1186/1743-7075-3-5.CrossRef Schlitt A, Blankenberg S, Yan D, von Gizycki H, Buerke M, Werdan K, Bickel C, Lackner KJ, Meyer J, Rupprecht HJ, Jiang XC: Further evaluation of plasma sphingomyelin levels as a risk factor for coronary artery disease. Nutr Metab (Lond). 2006, 3: 5-10.1186/1743-7075-3-5.CrossRef
15.
go back to reference Nelson JC, Jiang XC, Tabas I, Tall A, Shea S: Plasma sphingomyelin and subclinical atherosclerosis: findings from the multi-ethnic study of atherosclerosis. Am J Epidemiol. 2006, 163: 903-912. 10.1093/aje/kwj140.CrossRef Nelson JC, Jiang XC, Tabas I, Tall A, Shea S: Plasma sphingomyelin and subclinical atherosclerosis: findings from the multi-ethnic study of atherosclerosis. Am J Epidemiol. 2006, 163: 903-912. 10.1093/aje/kwj140.CrossRef
16.
go back to reference Yeboah J, McNamara C, Jiang XC, Tabas I, Herrington DM, Burke GL, Shea S: Association of plasma sphingomyelin levels and incident coronary heart disease events in an adult population: Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2010, 30: 628-633. 10.1161/ATVBAHA.109.199281.CrossRef Yeboah J, McNamara C, Jiang XC, Tabas I, Herrington DM, Burke GL, Shea S: Association of plasma sphingomyelin levels and incident coronary heart disease events in an adult population: Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2010, 30: 628-633. 10.1161/ATVBAHA.109.199281.CrossRef
17.
go back to reference Hojjati MR, Jiang XC: Rapid, specific, and sensitive measurements of plasma sphingomyelin and phosphatidylcholine. J Lipid Res. 2006, 47: 673-676.CrossRef Hojjati MR, Jiang XC: Rapid, specific, and sensitive measurements of plasma sphingomyelin and phosphatidylcholine. J Lipid Res. 2006, 47: 673-676.CrossRef
18.
go back to reference Hailemariam TK, Huan C, Liu J, Li Z, Roman C, Kalbfeisch M, Bui HH, Peake DA, Kuo MS, Cao G, Wadgaonkar R, Jiang XC: Sphingomyelin synthase 2 deficiency attenuates NFkappaB activation. Arterioscler Thromb Vasc Biol. 2008, 28: 1519-1526. 10.1161/ATVBAHA.108.168682.CrossRef Hailemariam TK, Huan C, Liu J, Li Z, Roman C, Kalbfeisch M, Bui HH, Peake DA, Kuo MS, Cao G, Wadgaonkar R, Jiang XC: Sphingomyelin synthase 2 deficiency attenuates NFkappaB activation. Arterioscler Thromb Vasc Biol. 2008, 28: 1519-1526. 10.1161/ATVBAHA.108.168682.CrossRef
19.
go back to reference Liu JC, Wang DM, Qian JN, Li YG, Wang LJ, Jiang XL, Zhai LL, Lu J, Qi P: [Changes of nitric oxide and endothelin serum level after carotid balloon denudation or stent assisted angioplasty: an experimental and clinical observation]. Zhonghua Wai Ke Za Zhi. 2009, 47: 423-426. Liu JC, Wang DM, Qian JN, Li YG, Wang LJ, Jiang XL, Zhai LL, Lu J, Qi P: [Changes of nitric oxide and endothelin serum level after carotid balloon denudation or stent assisted angioplasty: an experimental and clinical observation]. Zhonghua Wai Ke Za Zhi. 2009, 47: 423-426.
20.
go back to reference Lozanski G, Berthier F, Kushner I: The sphingomyelin-ceramide pathway participates in cytokine regulation of C-reactive protein and serum amyloid A, but not alpha-fibrinogen. Biochem J. 1997, 328 (Pt 1): 271-275.CrossRef Lozanski G, Berthier F, Kushner I: The sphingomyelin-ceramide pathway participates in cytokine regulation of C-reactive protein and serum amyloid A, but not alpha-fibrinogen. Biochem J. 1997, 328 (Pt 1): 271-275.CrossRef
21.
go back to reference Redfield MM, Jacobsen SJ, Burnett JC, Mahoney DW, Bailey KR, Rodeheffer RJ: Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003, 289: 194-202. 10.1001/jama.289.2.194.CrossRef Redfield MM, Jacobsen SJ, Burnett JC, Mahoney DW, Bailey KR, Rodeheffer RJ: Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003, 289: 194-202. 10.1001/jama.289.2.194.CrossRef
22.
go back to reference Liu B, Andrieu-Abadie N, Levade T, Zhang P, Obeid LM, Hannun YA: Glutathione regulation of neutral sphingomyelinase in tumor necrosis factor-alpha-induced cell death. J Biol Chem. 1998, 273: 11313-11320. 10.1074/jbc.273.18.11313.CrossRef Liu B, Andrieu-Abadie N, Levade T, Zhang P, Obeid LM, Hannun YA: Glutathione regulation of neutral sphingomyelinase in tumor necrosis factor-alpha-induced cell death. J Biol Chem. 1998, 273: 11313-11320. 10.1074/jbc.273.18.11313.CrossRef
23.
go back to reference Oral H, Dorn GW, Mann DL: Sphingosine mediates the immediate negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian cardiac myocyte. J Biol Chem. 1997, 272: 4836-4842. 10.1074/jbc.272.8.4836.CrossRef Oral H, Dorn GW, Mann DL: Sphingosine mediates the immediate negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian cardiac myocyte. J Biol Chem. 1997, 272: 4836-4842. 10.1074/jbc.272.8.4836.CrossRef
24.
go back to reference Amadou A, Nawrocki A, Best-Belpomme M, Pavoine C, Pecker F: Arachidonic acid mediates dual effect of TNF-alpha on Ca2+ transients and contraction of adult rat cardiomyocytes. Am J Physiol Cell Physiol. 2002, 282: C1339-1347.CrossRef Amadou A, Nawrocki A, Best-Belpomme M, Pavoine C, Pecker F: Arachidonic acid mediates dual effect of TNF-alpha on Ca2+ transients and contraction of adult rat cardiomyocytes. Am J Physiol Cell Physiol. 2002, 282: C1339-1347.CrossRef
25.
go back to reference Cailleret M, Amadou A, Andrieu-Abadie N, Nawrocki A, Adamy C, Ait-Mamar B, Rocaries F, Best-Belpomme M, Levade T, Pavoine C, Pecker F: N-acetylcysteine prevents the deleterious effect of tumor necrosis factor-(alpha) on calcium transients and contraction in adult rat cardiomyocytes. Circulation. 2004, 109: 406-411. 10.1161/01.CIR.0000109499.00587.FF.CrossRef Cailleret M, Amadou A, Andrieu-Abadie N, Nawrocki A, Adamy C, Ait-Mamar B, Rocaries F, Best-Belpomme M, Levade T, Pavoine C, Pecker F: N-acetylcysteine prevents the deleterious effect of tumor necrosis factor-(alpha) on calcium transients and contraction in adult rat cardiomyocytes. Circulation. 2004, 109: 406-411. 10.1161/01.CIR.0000109499.00587.FF.CrossRef
26.
go back to reference Pavoine C, Pecker F: Sphingomyelinases: their regulation and roles in cardiovascular pathophysiology. Cardiovasc Res. 2009, 82: 175-183.CrossRef Pavoine C, Pecker F: Sphingomyelinases: their regulation and roles in cardiovascular pathophysiology. Cardiovasc Res. 2009, 82: 175-183.CrossRef
27.
go back to reference Mrnka L, Novakova O, Pelouch V, Novak F: Phospholipid composition in the rat heart exposed to pressure overload from birth. Physiol Res. 1996, 45: 83-85. Mrnka L, Novakova O, Pelouch V, Novak F: Phospholipid composition in the rat heart exposed to pressure overload from birth. Physiol Res. 1996, 45: 83-85.
28.
go back to reference Liu J, Huan C, Chakraborty M, Zhang H, Lu D, Kuo MS, Cao G, Jiang XC: Macrophage sphingomyelin synthase 2 deficiency decreases atherosclerosis in mice. Circ Res. 2009, 105: 295-303. 10.1161/CIRCRESAHA.109.194613.CrossRef Liu J, Huan C, Chakraborty M, Zhang H, Lu D, Kuo MS, Cao G, Jiang XC: Macrophage sphingomyelin synthase 2 deficiency decreases atherosclerosis in mice. Circ Res. 2009, 105: 295-303. 10.1161/CIRCRESAHA.109.194613.CrossRef
29.
go back to reference Fan Y, Shi F, Liu J, Dong J, Bui HH, Peake DA, Kuo MS, Cao G, Jiang XC: Selective reduction in the sphingomyelin content of atherogenic lipoproteins inhibits their retention in murine aortas and the subsequent development of atherosclerosis. Arterioscler Thromb Vasc Biol. 2010, 30: 2114-2120. 10.1161/ATVBAHA.110.213363.CrossRef Fan Y, Shi F, Liu J, Dong J, Bui HH, Peake DA, Kuo MS, Cao G, Jiang XC: Selective reduction in the sphingomyelin content of atherogenic lipoproteins inhibits their retention in murine aortas and the subsequent development of atherosclerosis. Arterioscler Thromb Vasc Biol. 2010, 30: 2114-2120. 10.1161/ATVBAHA.110.213363.CrossRef
30.
go back to reference Skalen K, Gustafsson M, Rydberg EK, Hulten LM, Wiklund O, Innerarity TL, Boren J: Subendothelial retention of atherogenic lipoproteins in early atherosclerosis. Nature. 2002, 417: 750-754. 10.1038/nature00804.CrossRef Skalen K, Gustafsson M, Rydberg EK, Hulten LM, Wiklund O, Innerarity TL, Boren J: Subendothelial retention of atherogenic lipoproteins in early atherosclerosis. Nature. 2002, 417: 750-754. 10.1038/nature00804.CrossRef
31.
go back to reference Schissel SL, Keesler GA, Schuchman EH, Williams KJ, Tabas I: The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene. J Biol Chem. 1998, 273: 18250-18259. 10.1074/jbc.273.29.18250.CrossRef Schissel SL, Keesler GA, Schuchman EH, Williams KJ, Tabas I: The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene. J Biol Chem. 1998, 273: 18250-18259. 10.1074/jbc.273.29.18250.CrossRef
32.
go back to reference Schlitt A, Hojjati MR, von Gizycki H, Lackner KJ, Blankenberg S, Schwaab B, Meyer J, Rupprecht HJ, Jiang XC: Serum sphingomyelin levels are related to the clearance of postprandial remnantlike particles. J Lipid Res. 2005, 46: 196-200.CrossRef Schlitt A, Hojjati MR, von Gizycki H, Lackner KJ, Blankenberg S, Schwaab B, Meyer J, Rupprecht HJ, Jiang XC: Serum sphingomyelin levels are related to the clearance of postprandial remnantlike particles. J Lipid Res. 2005, 46: 196-200.CrossRef
33.
go back to reference Fan Y, Shi F, Liu J, Dong J, Bui HH, Peake DA, Kuo MS, Cao G, Jiang XC: Selective Reduction in the Sphingomyelin Content of Atherogenic Lipoproteins Inhibits Their Retention in Murine Aortas and the Subsequent Development of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2010 Fan Y, Shi F, Liu J, Dong J, Bui HH, Peake DA, Kuo MS, Cao G, Jiang XC: Selective Reduction in the Sphingomyelin Content of Atherogenic Lipoproteins Inhibits Their Retention in Murine Aortas and the Subsequent Development of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2010
Metadata
Title
Impact of sphingomyelin levels on coronary heart disease and left ventricular systolic function in humans
Authors
Xueying Chen
Aijun Sun
Yunzeng Zou
Junbo Ge
Jason M Lazar
Xian-Cheng Jiang
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Nutrition & Metabolism / Issue 1/2011
Electronic ISSN: 1743-7075
DOI
https://doi.org/10.1186/1743-7075-8-25

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