Mechanism of Atrial Fibrillation is Related to Changes of Type IV Collagen in Rheumatic Heart Valvular Disease

Abstract

PurposeAtrial fibrillation (AF) is a common complication in heart valvular disease and is associated with morphology and cell ultrastructure abnormality. We aimed to study the distribution of collagen types and to investigate the relationship between type IV collagen changes in the tissue of the right atrium and the development of permeant AF in patients with mitral valvular disease.MethodsThe atrial appendage obtained from patients with mitral valvular disease associated with either sinus rhythm (SR, n=26, right atrial tissue) or permanent AF (AF ≥6 months, n=36, right and left atrial tissue). One part of the sample was used for histological analysis, including iTRAQ proteomics, immunohistochemistry, immunofluorescence and transmission electron microscope; the other part was analyzed by qRT‐PCR and western blotting to observe the molecular level of type IV collagen.ResultsiTRAQ proteomic study showed that type IV collagen was up‐regulated in right and left atrial tissue. Type IV collagen was located around cardiomyocytes, especially on vascular basement membrane and myocardial cell membrane. The fluorescence intensity of type IV collagen increased in AF patients. Electron microscope revealed that there was a large number of immature fibrocytes among myocytes, likely immature type collagen IV. qRT‐PCR and western blots showed that the mRNA and protein of type IV collagen were significantly elevated in AF patients, especially in the left atrial tissue.ConclusionsOur study identified that the change of type IV collagen in the atrial appendage is related to the development of AF in the mitral valvular disease. The present study suggests that abnormality of the type IV collagen may play an important role in the structure and electrical signal in the heart valvular disease associated with AF.Support or Funding InformationSupported by National Natural Science Foundation of China (No.81170148), Zhejiang Provincial Natural Science Foundation (LY15H020008), Hangzhou Science and Technology Projects (20140633B12), National Science and Technology Major Project (2013ZX09303004‐005), & Tianjin Binhai Key Platform for Creative Research Program (2012‐BH110004), Binhai New Area Health Bureau (2012BWKZ008,2014BWKY002, 2014BWKY010), Tianjin Health Bureau (2013KZ009,2014KZ005).