Analysis of VNTR loci amplified by the polymerase chain reaction for investigating the origin of intimal smooth muscle cells in a coronary artery lesion developing after heart transplantation in man.

Focal intimal thickening is a feature of primary atherosclerotic coronary lesions and restenotic lesions following percutaneous transluminal coronary angioplasty and other forms of vascular intervention, where it is the nonspecific response of the vessel wall to injury. The principal cellular component of the coronary plaque is the smooth muscle cell.’ Whether the smooth muscle cell in human coronary lesions is derived from cells circulating in the blood or from the vessel wall itself remains a matter for debate. On the basis of animal studies, it is generally presumed that the tunica media or subintimal space is the source of intimal smooth muscle cells.2-5 However, there is sound experimental evidence that smooth muscle cells recognized in a vascular plaque may originate in mural thrombus and not in the adjacent vessel wall. 6-8 Regardless of their source, these cells would normally be indistinguishable. Atherosclerotic lesions developing in the coronary arteries after orthotopic heart transplantation provide a unique opportunity to pursue the origin of cells within the coronary atherosclerotic plaque, as the donor and recipient invariably differ in genotype. Genetic differences may be demonstrated by the electrophoretic analysis of alleles from the highly polymorphic variable number of tandem repeats (VNTR) gene loci that occur widely in the human genome.g,10 The Dl7S5/Dl7S30 VNTR locus, the DlS80/ DlS58 VNTR locus, and the Apo B 3’ VNTR locus (the hypervariable 3’ region of the apolipoprotein B gene) represent independent, highly polymorphic deoxyribonucleic