Molecular Mechanisms Of BFGF In Atrial Fibrosis In Patients With Atrial Fibrillation During Rheumatic Heart Disease

Objective To determine the molecular mechanisms involved in atrial fibrosis which occurs in patients with atrial fibrillation (AF) and to investigate their effects on the initiation and maintenance of AF.Methods The right atrial tissue samples were taken from 75 patients with rheumatic heart disease who underwent heart valve replacement surgery. 34 patients were in sinus rhythm, 11 patients had paroxysmal AF and 30 patients had persistent AF. Picrosirius red staining were used for quantitative analysis of collagen accumulation. The protein level of bFGF, FGFR1, HSPG,α-SMA were measured by immunohistochemistry and the mRNA level of collagen type I and type III, bFGF, FGFR1, HSPG,α-SMA were measured by semi-quantitative reverse transcription-poly merase chain reaction (RT-PCR) respectively.Results (1) Atrial fibrosis tissue content significantly increased in both the paroxysmal AF and persistent AF groups than that in the sinus rhythm group. The mRNA of collagen type I increased significantly in the persistent AF group followed by the paroxysmal AF group compared with the sinus rhythm group. The mRNA of collagen type III was slightly higher in both AF groups than that in the sinus rhythm group, but the differences were not statistically significant. Collagen volume fraction(CVF) and the mRNA of collagen type I significantly correlated with left atria(LA) dimension and AF duration. (2) bFGF expression at mRNA and protein level increased significantly in the persistent AF group followed by the paroxysmal AF group compared with the sinus rhythm group. FGFR1 expression at mRNA and protein level increased significantly in the persistent AF group followed by the paroxysmal AF group compared with the sinus rhythm group.HSPG expression at mRNA and protein level increased significantly in the persistent AF group followed by the paroxysmal AF group compared with the sinus rhythm group.α-SMA expression at mRNA and protein level increased significantly in the persistent AF group followed by the paroxysmal AF group compared with the sinus rhythm group.Conclutions The upregulation of bFGF gene expression may have contributed to the atrial structural remodeling during AF through enhanced collagen anabolic metabolism.