Abstract
The propensity to develop atherosclerosis varies markedly among different sites in the human vasculature. To determine a possible cause for such differences in atherosclerosis susceptibility, a proteomics-based approach was used to assess the extracellular proteoglycan core protein composition of intimal hyperplasia from both the atherosclerosis-prone internal carotid artery and the atherosclerosis-resistant internal thoracic artery. The intimal proteoglycan composition in these preatherosclerotic lesions was found to be more complex than previously appreciated with up to eight distinct core proteins present, including the large extracellular proteoglycans versican and aggrecan, the basement membrane proteoglycan perlecan, the class I small leucine-rich proteoglycans biglycan and decorin, and the class II small leucine-rich proteoglycans lumican, fibromodulin, and prolargin/PRELP (proline arginine-rich end leucine-rich repeat protein). Although most of these proteoglycans seem to be present in similar amounts at the two locations, there was a selective enhanced deposition of lumican in the intima of the atherosclerosis-prone internal carotid artery compared with the intima of the atherosclerosis-resistant internal thoracic artery. The enhanced deposition of lumican in the intima of an atherosclerosis prone artery has important implications for the pathogenesis of atherosclerosis.
Highlights
The propensity to develop atherosclerosis varies markedly among different sites in the human vasculature
Because proteoglycans deposited in intimal hyperplasia are believed to play a central role in the development of atherosclerosis, it was hypothesized that differences in the intimal extracellular proteoglycan composition may be at least partly responsible for the marked variation in susceptibility to atherosclerosis among different sites in the vasculature
The results presented here indicate that in addition to versican, aggrecan is a large extracellular proteoglycan contributing to the structure of the matrix in the proteoglycan-rich zone of the inner intima
Summary
The propensity to develop atherosclerosis varies markedly among different sites in the human vasculature. It is noteworthy that these immunohistochemical analyses have indicated that versican, biglycan, and lumican are present in both atherosclerotic lesions and preatherosclerotic intimal hyperplasia. To gain a more complete understanding of the extracellular proteoglycan core protein composition of human vascular intima and how this composition may vary at different sites in the circulation, a proteomics-based approach was performed using both the atherosclerosisprone internal carotid artery and the atherosclerosis-resistant internal thoracic artery.
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