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 cells

Journal of Vascular Surgery
Richard D KenagyMichael Sobel

Abstract

Cyclin-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. Human saphenous vein adventitial cells and intimal/medial smooth muscle cells (SMCs) were derived from explants obtained at the time of lower extremity bypass operations. We determined the following in adventitial cells and SMCs as a function of the p27 SNP genotype: (1) p27 promoter activity, (2) p27 messenger (m)RNA and protein levels, and (3) growth and collagen gel contraction. Deoxyribonuclease I footprinting was also performed in adventitial cells and SMCs. p27 promoter activity, deoxyribonuclease I footprinting, p27 mRNA levels, and p27 protein levels demonstrated that the p27 SNP is functional in adventitial cells and SMCs. Both cell types with the graft failure protective AA genotype had more p27 mRNA and protein. As predicted because of higher levels of p27 protein, adventitial cells with the AA genotype grew slower than those of the CC genotype. Unexpectedly, SMCs did not show this genotype-dependent growth response. These re...Continue Reading

Citations

Jan 3, 2020·International Journal of Molecular Medicine·Wenjun RenHongrong Li
Mar 30, 2018·Frontiers in Cardiovascular Medicine·Matthijs Steven Ruiter, Maurizio Pesce
Jun 20, 2018·Journal of Vascular Surgery·Michael SobelRichard D Kenagy

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.