The relationship between the number of preprocedural circulating endothelial progenitor cells and angiographic restenosis following coronary artery stent placement.

Objective: In animals, endothelial progenitor cells (EPCs) beneficially influence the repair of the coronary vessel wall after damage by stent placement. However, their role in humans is less well understood. In the present study, the authors aimed to evaluate the relationship between the number of preprocedural EPCs defined as CD34+/KDR+/CD133+ cells and angiographic late loss as a measure of the growth of in-stent intimal hyperplasia.

Activin A induces a non-fibrotic phenotype in smooth muscle cells in contrast to TGF-β.

Aims: Activin A and transforming growth factor-β1 (TGF-β1) belong to the same family of growth and differentiation factors that modulate vascular lesion formation in distinct ways, which we wish to understand mechanistically.

Methods And Results: We investigated the expression of cell-surface receptors and activation of Smads in human vascular smooth muscle cells (SMCs) and demonstrated that activin receptor-like kinase-1 (ALK-1), ALK-4, ALK-5 and endoglin are expressed in human SMCs. As expected, TGF-β1 activates Smad1 and Smad2 in these cells.

Erythropoietin accelerates smooth muscle cell-rich vascular lesion formation in mice through endothelial cell activation involving enhanced PDGF-BB release.

In this study, the effect of human erythropoietin Delta (Epo) on smooth muscle cell (SMC)-rich lesions was evaluated. Mice, of which the left carotid artery was ligated, were treated with suberythropoietic as well as erythropoietic doses of Epo and both doses of Epo enhanced SMC-rich lesion formation. No association was observed between hemoglobin levels and lesion size.

p27kip1-838C>A single nucleotide polymorphism is associated with restenosis risk after coronary stenting and modulates p27kip1 promoter activity.

Background: The cyclin-dependent kinase inhibitor p27(kip1) is a key regulator of smooth muscle cell and leukocyte proliferation in vascular disease, including in-stent restenosis. We therefore hypothesized that common genetic variations or single nucleotide polymorphisms in p27(kip1) may serve as a useful tool in risk stratification for in-stent restenosis.

Methods And Results: Three single nucleotide polymorphisms concerning the p27(kip1) gene (-838C>A, rs36228499; -79C>T, rs34330; +326G>T, rs2066827) were determined in a cohort of 715 patients undergoing coronary angioplasty and stent placement.

Five new mouse susceptibility to colon cancer loci, Scc11-Scc15.

Although several genes causing familial cancer syndromes have been identified, susceptibility to sporadic cancer remains unsolved. Animal experiments have demonstrated a large number of quantitative trait loci affecting cancer susceptibility. Previously, we described in mouse strain CcS-19/Dem five susceptibility to colon cancer (Scc) loci, Scc1-Scc5 controlling tumor numbers.

LOH of PTPRJ occurs early in colorectal cancer and is associated with chromosomal loss of 18q12-21.

Recently, the gene PTPRJ (protein tyrosine phosphatase receptor type J) was identified as the candidate gene for the mouse colon cancer susceptibility locus Scc1. Its human homologue PTPRJ is frequently deleted in several cancer types, including colorectal cancer. To elucidate the role of PTPRJ loss in different stages of colorectal cancer and in its pathways of progression, we expanded the previously published comparative genomic hybridization results with novel data on loss of heterozygosity (LOH) at the PTPRJ locus.

Ptprj is a candidate for the mouse colon-cancer susceptibility locus Scc1 and is frequently deleted in human cancers.

Only a small proportion of cancers result from familial cancer syndromes with Mendelian inheritance. Nonfamilial, 'sporadic' cancers, which represent most cancer cases, also have a significant hereditary component, but the genes involved have low penetrance and are extremely difficult to detect. Therefore, mapping and cloning of quantitative trait loci (QTLs) for cancer susceptibility in animals could help identify homologous genes in humans.