Invited commentary

Abstract

Autogenous vein bypass grafting remains an important therapeutic option for patients with peripheral vascular disease. These vein grafts are durable; however, the development of de novo stenosis within the graft occurs in 30% to 50% of patients within the first several years. Despite multiple therapeutic interventions and vein graft manipulations, the incidence of vein graft disease has not changed over the last 30 years. Basic research has focused on endothelial cells, smooth muscle cells, and extracellular matrix as the responsible culprits for the intimal hyperplastic lesion. However, studies have now shown that the adventitial layer may have a more dynamic role in the intimal hyperplastic lesion. Furthermore, recent studies have demonstrated the potential role of genetic variability in the p27 Kip1 gene as a determinant of clinical outcomes in patients with cardiovascular disease and after clinical interventions. The authors present a provocative in vitro study of human venous adventitial and smooth muscle cells that shows that the p27 single nucleotide polymorphism (p27 KIP1-838C>A) is functional and that the levels of p27 messenger RNA and protein were higher in the cells with the AA genotype compared with the CC genotype. Knockdown of p27 increases growth of both cell types with the AA genotype but not those with the CC genotype. What, however, is groundbreaking in their study is the differential effect of the p27 single nucleotide polymorphism on adventitial cell growth. They noted that adventitial cells of the AA genotype grew significantly more slowly than those with the CC genotype. In this study, only the adventitial cells, and not the smooth muscle cells, are responsible to the inhibitory effects of the protective AA genotype in cell growth. The adventitial layer has been noted to have vascular fibroblasts, perivascular adipocytes, and progenitor cells, which have been shown to affect vascular smooth muscle cell phenotype and growth. How these components interact to achieve the complex intimal hyperplastic lesion is still not known. However, using mouse model technology and lineage tracing technology to discover the cells or cells that are really responsible for the intimal hyperplastic lesion and, therefore, more precisely targeting treatment, could one day allow for the treatment of this disease that has been plaguing long-term vascular surgical outcomes for the last 40 years. The opinions or views expressed in this commentary are those of the authors and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery. A single nucleotide polymorphism of cyclin-dependent kinase inhibitor 1B (p27Kip1) associated with human vein graft failure affects growth of human venous adventitial cells but not smooth muscle cellsJournal of Vascular SurgeryVol. 67Issue 1PreviewCyclin-dependent kinase inhibitor 1B (p27Kip1) is a cell-cycle inhibitor whose -838C>A single nucleotide polymorphism (rs36228499; hereafter called p27 SNP) has been associated with the clinical failure of peripheral vein grafts, but the functional effects of this SNP have not been demonstrated. Full-Text PDF Open Archive