Kinetics of selected serum markers of fibrosis in patients with dilated cardiomyopathy and different grades of diastolic dysfunction of the left ventricle

Abstract

Background: Fibrosis of the extracellular matrix (ECM) in dilated cardiomyopathy (DCM) is common and compromises both systolic and diastolic function. The aim of this study was to investigate the kinetics of ECM fibrosis markers over a 12 month follow-up in patients with DCM based on the severity of diastolic dysfunction (DD). Methods: Seventy consecutive DCM patients (48 ± 12.1 years, ejection fraction 24.4 ± 7.4%) were included in the study. The grade of DD was determined using the ASE/EACVI algorithm. Markers of ECM fibrosis were measured at baseline and at 3 and 12 month follow-ups: collagen type I and III (PICP, PINP, PIIICP, PIIINP), transforming growth factor beta-1 (TGF1-b), connective tissue growth factor (CTGF) and galectin-3 were measured. Results: Patients were divided into three groups according to DD severity: 30 patients with grade I, 18 with grade II and 22 with grade III of DD. Levels of PICP, PINP were increased over a 12-month period, while PIIINP decreased and PIIICP unchanged. Levels of TGF1-b decreased from the 3 to the 12-month points in grade I and II DD, and in grade III they remained unchanged. Levels of CTGF decreased over 12 months in grade III DD but were unchanged in grades I and II. Galectin-3 levels remained the same over all observation periods, irrespective of DD grade. Conclusions: Regardless of the DD grade, markers of collagen type I synthesis increased, markers of collagen type III decreased. Levels of TGF and CTGF had a tendency to decrease. Galectin-3 was revealed not to be a marker discriminating the severity of DD.

Blocking CCN2 Reduces Established Bone Loss Induced by Prolonged Intense Loading by Increasing Osteoblast Activity in Rats

“…We did not assay for PINP in this study, a marker of collagen type I synthesis by many cell types, including osteoblasts, fibroblasts, and other cells that make collagen type I. PINP has been shown to be an excellent serum biomarker of fibrosis (ie, collagen type I synthesis) in patients with dilated cardiomyopathy and different grades of diastolic dysfunction of the left ventricle, [ 62 ] idiopathic pulmonary fibrosis, [ 63 ] liver matrix remodeling with fibrosis, [ 64 ] and muscle fibrosis associated with muscular dystrophies and other myopathies. [ 65 ] Because our model induces muscle, tendon, and nerve fibrosis, we see serum increases of PINP as part of the muscle and other soft tissue collagen production and fibrosis, [ 27 ] a finding that confounds the interpretation of PINP as a marker of bone formation in this model.…”

Robust Rank Aggregation and Least Absolute Shrinkage and Selection Operator Analysis of Novel Gene Signatures in Dilated Cardiomyopathy

“…Interestingly, the results of the present study also suggest a positive correlation between OMD and COL1A1, and its functional analysis mainly involved in extracellular matrix processes. Extracellular matrix fibrosis is regarded as an important process in the development of DCM ( 55 ). Therefore, targeted OMD gene therapy may be a potential therapeutic strategy for dilated cardiomyopathy.…”

Efficacy of L‐Carnitine for Dilated Cardiomyopathy: A Meta‐Analysis of Randomized Controlled Trials

“…More importantly, TGF- β 1 plays an important role in myocardial cell hypertrophy and cardiac interstitial growth [ 43 ]. Besides, DCM is associated with raised levels of TGF- β 1 [ 44 ].…”