The macrophage as an initiator of atherosclerosis

1. Heparan sulfate proteoglycan in the basal lamina of smooth muscle cells is important in the maintenance of the 'contractile', high volume fraction of myofilaments (Vvmyo) phenotype. The mechanism by which this occurs may involve the continuous internalization of heparan sulfate by the smooth muscle cells themselves. 2. One macrophage can degrade all the heparan sulfate from three smooth muscle cells by the action of heparan sulfate-degrading enzymes in their lysosomes, thus leaving none available for internalization by the smooth muscle cell until it has synthesized more, and leading to the induction of smooth muscle phenotypic change from a high Vvmyo to a low Vvmyo. 3. In this altered phenotype the smooth muscle cells proliferate in response to mitogens, synthesize large amounts of extracellular matrix and accumulate lipid, all characteristics of the smooth muscle cell in developing atheroma.