Anti-Collagen Type VI polyclonal antibody

Metabolic disorders, such as obesity and type 2 diabetes, are associated with an increased risk of cardiomyopathy. To date, microRNA (miRNAs) functions in cardiac remodeling induced by obesity remain to be elucidated. We found that rats fed a high fat diet (HFD) manifested cardiac fibrosis and LV dysfunction. In the heart of rats fed HFD, the phosphorylation levels of Smad 2 and the expression of fibrotic genes, such as connective tissue growth factor, collagen-1 alpha 1 (Col1 alpha 1), Col3 alpha 1, and Col4 alpha 1, were up-regulated, which accompanied by an increase in Smad 7 protein levels, but not its mRNA levels. Using miRNA microarray analysis, we showed that the miRNA miR-410-5p inhibited the protein expression of Smad 7, thus increasing the phosphorylation levels of Smad 2. Overexpression of miR410-5p promoted cardiac fibrosis in rats fed normal diet, whereas inhibition of miR-410-5p by way of miR-410-5p antimiR suppressed cardiac fibrosis in rats fed HFD. Finally, our data revealed that miR410-5p from the kidney and adipose tissues was probably transferred to heart to induce cardiac fibrosis. Taken together, our study characterizes an endocrine mechanism in which adipose-or kidney-derived circulating miR-410-5p regulates metabolic disorders-mediated cardiac remodeling by activating the TGF beta/Smad signaling in heart.

Hepatitis C virus (HCV) infection and its recurrence after orthotopic liver transplantation (OLT) are associated with the remodeling of extracellular matrix (ECM) components [ particularly collagen (Col)], which leads to fibrosis. Our aim was to determine whether the development of antibodies (Abs) to self-antigen Col in HCV-infected patients correlates with the fibrosis stage and the peripheral cytokine response. Patients with chronic HCV infection, patients with HCV recurrence after OLT who had undergone a biopsy procedure, and healthy control subjects were enrolled. The HCV subjects (n = 70) were stratified as follows: (1) a non-OLT group without fibrosis (Scheuer stages 0-2), (2) a non-OLT group with fibrosis (Scheuer stages 3-4), (3) a post-OLT group without fibrosis (Scheuer stages 0-2), and (4) a post-OLT group with fibrosis (Scheuer stages 3-4). Serum samples were analyzed for Abs against Col1, Col2, Col4, Col5, and vimentin with enzyme-linked immunosorbent assays. Serum levels of cytokines were measured with multiplex bead immunoassays. The levels of Abs to Col1 were higher in the fibrosis groups versus the no-fibrosis groups and the controls for both non-OLT patients (P < 0.001) and post-OLT patients (P = 0.01). There were increased levels of Abs to Col2, Col4, Col5, and vimentin in the non-OLT fibrosis group (Col2, P = 0.0001; Col4, P = 0.122; Col5, P < 0.0001; vimentin, P = 0.36) and in the post-OLT fibrosis group (Col2, P = 0.006; Col4, P = 0.19; Col5, P < 0.0001; vimentin, P = 0.24) in comparison with the no-fibrosis groups. The non-OLT and post-OLT fibrosis groups demonstrated significantly higher T helper 2 (T(h)2) and T helper 17 (T(h)17) cytokine levels and lower T helper 1 cytokine levels in comparison with the no-fibrosis groups. Our results demonstrate that in HCV-infected patients, the levels of Abs to ECM Col1, Col2, and Col5 positively correlate with liver fibrosis, which is associated with a predominantly Th2 and Th17 cytokine profile. Liver Transpl 17:814-823, 2011. (C) 2011 AASLD.