Sphingomyelinase, an enzyme implicated in atherogenesis, is present in atherosclerotic lesions and binds to specific components of the subendothelialextracellular matrix

Atherosclerotic lesions contain an extracellular sphingomyelinase (SMase) a ctivity that hydrolyzes the sphingomyelin of subendothelial low density lip oprotein (LDL), This SMase activity may promote atherosclerosis by enhancin g subendothelial LDL retention and ag,aggregation, foam cell formation, and possibly other atherogenic processes. The results of recent cell-culture s tudies have led to the hypothesis that a specific molecule called secretory SMase (S-SMase) is responsible for the SMase activity known to be in lesio ns, although its presence in atheromata had not been examined directly. Her ein we provide immunohistochemical and biochemical support for this hypothe sis. First, 2 different antibodies against S-SMase detected extracellular i mmunoreactive protein in the intima of mouse, rabbit, and human atheroscler otic lesions. Much of this material in lesions appeared in association with the subendothelial matrix. Second, binding studies in vitro demonstrated t hat I-125-S-SMase adheres to the extracellular matrix of cultured aortic sm ooth muscle and endothelial cells, specifically to the laminin and collagen components. Third, in its bound state, S-SMase retains substantial enzymat ic activity against lipoprotein substrates, Overall, these data support the hypothesis that S-SMase is an extracellular arterial wall SMase that contr ibutes to the hydrolysis of the sphingomyelin of subendothelial LDL. S-SMas e may therefore be an important participant in atherogenesis through local enzymatic effects that stimulate subendothelial retention and aggregation o f atherogenic lipoproteins.