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Am J Cardiovasc Dis 2013;3(1):17-26
www.AJCD.us /ISSN:2160-200X/AJCD1211005
Review Article
Interaction between sphingomyelin and oxysterols
contributes to atherosclerosis and sudden death
Fred A Kummerow
Burnsides Research Laboratory, Department of Comparative Biosciences, College of Veterinary Medicine, Univer-
sity 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 arte-
rial 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 contrib-
uting 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.
Keywords: Sphingomyelin, oxysterols, thromboxane, prostacyclin, trans fatty acids, calcium, stenosis
