Atherosclerosis is most often the culprit in coronary heart disease and other cardiovascular conditions, and a large aggregation of perlecan protein is symptomatic of advanced atherosclerotic plaques. VSMCs are the producers of the perlecan in this condition, meaning that a good deal of research has been focused on understanding the means of perlecan upregulation in this condition. In a test of the effect of circulating nonesterified fatty acids (symptomatic of diabetes and atherogenesis) on perlecan expression by VSMCs, expression did not change when compared to control cells. This was in contrast to a 2-10-fold increase in expression of other basement membrane proteoglycans. Thrombin is another marker associated with atherogenesis and procoagulation, and it selectively upregulates production of perlecan but not other proteoglycans in human VSMCs in culture. It is suggested that this effect is only seen when VSMCs reach confluence, but not prior to confluence. This concept is similar to previously mentioned studies showing that perlecan is only produced by VSMCs once they have ceased proliferation during development. Another marker in the atherosclerotic pathway is angiotensin II, which also upregulates perlecan expression in VSMCs in culture. Given the prominence of perlecan expression in atherosclerosis there is potential for therapy based upon perlecan expression and research may eventually proceed in that direction.