Vascular smooth muscle cells orchestrate the assembly of type I collagen via alpha2beta1 integrin, RhoA, and fibronectin polymerization.

Assembly of collagen into fibrils is widely studied as a spontaneous and entropy-driven process. To determine whether vascular smooth muscle cells (SMCs) impact the formation of collagen fibrils, we microscopically tracked the conversion of soluble to insoluble collagen in human SMC cultures, using fluorescent type I collagen at concentrations less than that which supported self-assembly. Collagen microaggregates were found to form on the cell surface, initially as punctate collections and then as an increasingly intricate network of fibrils.

Cloning of a novel prolyl 4-hydroxylase subunit expressed in the fibrous cap of human atherosclerotic plaque.

Background: The production of collagen is fundamental to atherosclerosis and critically dependent on posttranslational modification by prolyl 4-hydroxylase.

Methods And Results: We report the cloning of a novel prolyl 4-hydroxylase catalytic (alpha) subunit from human vascular smooth muscle cells. The peptide displayed conservation of critical residues for interacting with Fe2+ and 2-oxoglutarate, essential cosubstrates for prolyl 4-hydroxylase activity.

Transforming growth factor-beta1 inhibits macrophage cholesteryl ester accumulation induced by native and oxidized VLDL remnants.

Transforming growth factor beta1 (TGF-beta1) is secreted by various cells, including macrophages, smooth muscle cells, and endothelial cells. TGF-beta1 is present in atherosclerotic lesions, but its role in regulating macrophage foam cell formation is not understood. Hypertriglyceridemic very low density lipoprotein (VLDL) remnants (VLDL-REMs) in their native or oxidized form will induce cholesteryl ester (CE) and triglyceride (TG) accumulation in macrophages.

Clinical and molecular correlations in spinocerebellar ataxia type 6: a study of 24 Dutch families.

Background: Autosomal dominant cerebellar ataxias (ADCAs), or spinocerebellar ataxias (SCAs), are a heterogeneous group of neurodegenerative disorders. Mild CAG repeat expansions in the alpha(1A) voltage-dependent calcium channel gene are associated with SCA type 6 (SCA6).

Objective: To obtain further insight into the contribution of SCA6 mutations to the phenotypic variability in Dutch patients with ataxia.

Innate diversity of adult human arterial smooth muscle cells: cloning of distinct subtypes from the internal thoracic artery.

Vascular smooth muscle cells (SMCs) perform diverse functions and this functional heterogeneity could be based on differential recruitment of distinct SMC subsets. In humans, however, there is little support for such a paradigm, partly because isolation of pure human SMC subsets has proven difficult. We report the cloning of 12 SMC lines from a single fragment of human internal thoracic artery and the elucidation of 2 distinct cellular profiles.

Phenylketonuria in The Netherlands: 93% of the mutations are detected by single-strand conformation analysis.

Single-strand conformational analysis was used to screen for genetic defects in all thirteen exons of the phenylalanine hydroxylase gene (PAH) in phenylketonuria and hyperphenylalaninemia patients in the Netherlands. Exons that showed a bandshift were sequenced directly. In this way, we were able to identify 93% of the PAH mutations in a panel of 34 patients.