PMID: 9546352Apr 18, 1998Paper

Clonal architecture of normal and atherosclerotic aorta: implications for atherogenesis and vascular development

The American Journal of Pathology
I M ChungC E Murry

Abstract

X chromosome inactivation studies indicate that smooth muscle cells in human atherosclerosis are monoclonal. Monoclonality could arise either by 1) proliferation of a single cell in the adult intima, eg, by selection or mutation, or 2) proliferation of many cells within a large, pre-existing clonal patch that formed during development. To determine whether clonal expansion occurs concomitantly with plaque growth or as part of normal development, X chromosome inactivation patterns were mapped in microdissected samples of aortic smooth muscle, using the human androgen receptor locus as a marker. As expected, 43% of plaque samples were skewed toward one X chromosome, indicating a monoclonal population. Surprisingly, 25% of normal medial samples and 31% of diffuse intimal thickening samples also were skewed toward one X chromosome, indicating a relatively large patch size. Furthermore, 30% of diffuse intimal thickening and 22% of medial samples showed contiguous regions of 4 mm skewed to the same allele, showing that patch length often exceeded 4 mm. Intima and overlying media typically were skewed to the same allele (73% concordance), suggesting common cells of origin. Because patch size is large in normal arteries, X-inactivation...Continue Reading

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