Am J Cardiovasc Dis 2013;3(1):17-26
Review Article
Interaction between sphingomyelin and oxysterols contributes to
ath-erosclerosis and sudden death
Fred A Kummerow
Burnsides Research Laboratory, Department of Comparative Biosciences, College of Veterinary Medicine, University of
Illinois, 1208 W. Pennsylvania Avenue, Urbana, IL 61801, USA
Received November 26, 2012; Accepted January 23, 2013; Epub February 17, 2013; Published February 27, 2013
Abstract: Despite major public health efforts, coronary heart disease continues to be the leading cause of death in the
United States. Oxidized lipids contribute to heart disease both by increasing deposition of calcium on the arterial wall, a
major hallmark of atherosclerosis, and by interrupting blood flow, a major contributor to heart attack and sudden death.
Oxidized cholesterol (oxysterols) enhances the production of sphingomyelin, a phospholipid found in the cellular
membranes of the coronary artery. This increases the sphingomyelin content in the cell membrane, which in turn
enhances the interaction between the membrane and ionic calcium (Ca2+), thereby increasing the risk of arterial
calcification. Patients undergoing bypass surgery had greater concentrations of oxysterols in their plasma than cardiac
catheterized controls with no stenosis, and had five times more sphingomyelin in their arteries than in the artery of the
placenta of a newborn. The oxysterols found in the plasma of these patients were also found in the plasma of rabbits that
had been fed oxidized cholesterol and in frying fats and powdered egg yolk intended for human consumption. Together
these findings suggest that oxysterols found in the diet are absorbed and contribute to arterial calcification. Oxidized
low-density lipoprotein (OxLDL) further contributes to heart disease by increasing the synthesis of thromboxane in
platelets, which increases blood clotting. Cigarette smoke and trans fatty acids, found in partially hydrogenated soybean
oil, both inhibit the synthesis of prostacyclin, which inhibits blood clotting. By increasing the ratio of thromboxane to
prostacyclin, these factors interact to interrupt blood flow, thereby contributing to heart attack and sudden death. Levels of
oxysterols and OxLDL increase primarily as a result of three diet or lifestyle factors: the consumption of oxysterols from
commercially fried foods such as fried chicken, fish, and french fries; oxidation of cholesterol in vivo driven by consumption
of excess polyunsaturated fatty acids from vegetable oils; and cigarette smoking. Along with the consumption of trans fatty
acids from partially hydrogenated vegetable oil, these diet and lifestyle factors likely underlie the persistent national burden
of heart disease. (AJCD1211005).
Keywords: Sphingomyelin, oxysterols, thromboxane, prostacyclin, trans fatty acids, calcium, stenosis
Address correspondence to: Dr. Fred A Kummerow, Burnsides Research Laboratory, 1208 W. Pennsylvania Avenue,
Urbana, IL 61801, USA. Tel: 217-344-6380; Fax: 217-333-7370; E-mail: fkummero@illinois.edu
Review Article
Interaction between sphingomyelin and oxysterols contributes to
ath-erosclerosis and sudden death
Fred A Kummerow
Burnsides Research Laboratory, Department of Comparative Biosciences, College of Veterinary Medicine, University of
Illinois, 1208 W. Pennsylvania Avenue, Urbana, IL 61801, USA
Received November 26, 2012; Accepted January 23, 2013; Epub February 17, 2013; Published February 27, 2013
Abstract: Despite major public health efforts, coronary heart disease continues to be the leading cause of death in the
United States. Oxidized lipids contribute to heart disease both by increasing deposition of calcium on the arterial wall, a
major hallmark of atherosclerosis, and by interrupting blood flow, a major contributor to heart attack and sudden death.
Oxidized cholesterol (oxysterols) enhances the production of sphingomyelin, a phospholipid found in the cellular
membranes of the coronary artery. This increases the sphingomyelin content in the cell membrane, which in turn
enhances the interaction between the membrane and ionic calcium (Ca2+), thereby increasing the risk of arterial
calcification. Patients undergoing bypass surgery had greater concentrations of oxysterols in their plasma than cardiac
catheterized controls with no stenosis, and had five times more sphingomyelin in their arteries than in the artery of the
placenta of a newborn. The oxysterols found in the plasma of these patients were also found in the plasma of rabbits that
had been fed oxidized cholesterol and in frying fats and powdered egg yolk intended for human consumption. Together
these findings suggest that oxysterols found in the diet are absorbed and contribute to arterial calcification. Oxidized
low-density lipoprotein (OxLDL) further contributes to heart disease by increasing the synthesis of thromboxane in
platelets, which increases blood clotting. Cigarette smoke and trans fatty acids, found in partially hydrogenated soybean
oil, both inhibit the synthesis of prostacyclin, which inhibits blood clotting. By increasing the ratio of thromboxane to
prostacyclin, these factors interact to interrupt blood flow, thereby contributing to heart attack and sudden death. Levels of
oxysterols and OxLDL increase primarily as a result of three diet or lifestyle factors: the consumption of oxysterols from
commercially fried foods such as fried chicken, fish, and french fries; oxidation of cholesterol in vivo driven by consumption
of excess polyunsaturated fatty acids from vegetable oils; and cigarette smoking. Along with the consumption of trans fatty
acids from partially hydrogenated vegetable oil, these diet and lifestyle factors likely underlie the persistent national burden
of heart disease. (AJCD1211005).
Keywords: Sphingomyelin, oxysterols, thromboxane, prostacyclin, trans fatty acids, calcium, stenosis
Address correspondence to: Dr. Fred A Kummerow, Burnsides Research Laboratory, 1208 W. Pennsylvania Avenue,
Urbana, IL 61801, USA. Tel: 217-344-6380; Fax: 217-333-7370; E-mail: fkummero@illinois.edu
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