Atherosclerosis Sphingomyelin

Park TS, Panek RL, Rekhter MD, Mueller SB, Rosebury WS, Robertson A, Hanselman JC, Kindt E, Homan R, Karathanasis SK. Modulation of lipoprotein metabolism by inhibition of sphingomyelin synthesis in ApoEl knockout mice. Atherosclerosis 2006 189 264-272. 

Atherosclerosis is believed to be predominantly an inflammatory condition produced as a response to injury (Elkind, 2006). Atherosclerosis is defined by the accumulation in the arterial intima of mainly low-density lipoprotein (LDL)-derived lipids along with apolipoprotein B-lOO (apoBlOO). LDL is the major carrier of cholesterol in the circulation and is composed of one apoB-100 together with phosphatidylcholine (PC), sphingomyelin (SM) and unesterified cholesterol (500 200 400 molecules respectively) constituting a surface film surrounding a core of cholesteryl esters and triacylglycerols. 

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 163(2006) 903-912. 

I. Tabas and co-workers have proposed a role of secretory ASMase in atherosclerosis (Tabas, 1999 Tabas et ah, 2007) They reported that the enzyme can be secreted from cultured vascular endothelial cells in a form that is only partially dependent on Zn (Marathe et ah, 1998) and can cleave sphingomyelin on the surface of atherogenic lipoproteins even at pH 7.5, leading to fusion and aggregation of the lipoprotein particles (Schissel et ah, 1998b). It is not known how this form of the enzyme may differ on the molecular level from the strictly Zn-dependent ASMase circulating in human blood mentioned above. 

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