(C) 2015 Elsevier Inc. All rights reserved.”
“Background. Calcific aortic valve disease (CAVD) is the most common cause of acquired valve disease. Initial phases of CAVD include thickening of the cusps, whereas advanced stages are associated with biomineralization and reduction of the aortic valve area. These conditions are known as aortic valve SN-38 sclerosis (AVSc) and aortic valve stenosis (AVS), respectively. Because of its asymptomatic presentation, little is known about the molecular determinants of AVSc. The aim of this study was to correlate plasma and tissue osteopontin (OPN) levels with echocardiographic evaluation for the identification of asymptomatic patients at

risk for CAVD. In addition, our aim was to analyze the differential expression and biological function of OPN splicing variants as biomarkers of early and late stages of CAVD.\n\nMethods. From January 2010 to February 2011, 310 patients were enrolled in the study. Patients were divided into 3 groups based on transesophageal echocardiographic (TEE) evaluation: controls (56 patients), AVSc (90 patients), and AVS (164 patients). Plasma and tissue OPN levels were measured selleck compound by immunohistochemical evaluation, enzyme-linked immunosorbent assay (ELISA), and real-time quantitative polymerase chain reaction (qPCR).\n\nResults. Patients with AVSc and AVS have higher OPN levels compared

with controls. OPN levels are elevated in asymptomatic patients with AVSc with no appearance of calcification during TEE evaluation. OPN splicing variants OPN-a, OPN-b, and OPN-c are differentially expressed during CAVD progression and are able to inhibit biomineralization in a cell-based biomineralization assay.\n\nConclusions. The analysis of the differential expression of OPN splicing variants during CAVD may help in developing diagnostic

SRT2104 mouse and risk stratification tools to follow the progression of asymptomatic aortic valve degeneration. (Ann Thorac Surg 2012; 93:79-86) (C) 2012 by The Society of Thoracic Surgeons”
“Degradation of fibrillar collagens is important in many physiological and pathological events. These collagens are resistant to most proteases due to the tightly packed triple-helical structure, but are readily cleaved at a specific site by collagenases, selected members of the matrix metalloproteinases (MMPs). To investigate the structural requirements for collagenolysis, varying numbers of GXY triplets from human type III collagen around the collagenase cleavage site were inserted between two triple helix domains of the Scl2 bacterial collagen protein. The original bacterial CL domain was not cleaved by MMP-1 (collagenase 1) or MMP-13 (collagenase 3). The minimum type III sequence necessary for cleavage by the two collagenases was 5 GXY triplets, including 4 residues before and 11 residues after the cleavage site (P4-P11′).