Gene Expression Of PDGF And PDGFR In Patients With Chronic Atrial Fibrillation

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 before extracorporeal circulation. 34 patients were in sinus rhythm, 11 patients had paroxysmal AF and 30 patients had chronic AF. Picrosirius red staining was used for quantitative analysis of collagen accumulation. The mRNA level of collagen type I and type III,α-SMA,PDGF-AA,PDGF-BB,PDGFR -αα,PDGFR-ββwere measured by semi-quantitative reverse transcription-poly merase chain reaction (RT-PCR) and The protein expression and disposition ofα-SMA, PDGF-AA,PDGF-BB,PDGFR -αα,PDGFR -ββwere measured by immunohistochemistry respectively.Results (1)Atrial fibrosis tissue content significantly increased in both the paroxysmal AF and chronic 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)The mRNA and protein level of PDGF-BB,PDGFR-ββandα-SMA increased significantly in the paroxysmal AF group compared with the sinus rhythm group(P<0.01). The mRNA and protein level of PDGF-AA,PDGFR-ααhave no difference. The mRNA and protein level of PDGF-BB,PDGFR-ββandα-SMA increased significantly in the chronic AF group compared with the sinus rhythm group(P<0.001). The mRNA and protein level of PDGF-AA,PDGFR-ααwas slightly higher in chronic AF groups than that in the sinus rhythm group , but the differences were not statistically significant. (3) The mRNA and protein level of collagen type I were significant correlated with PDGF-BB,PDGFR-ββandα-SMA.Conclutions Significant fibrosis which correlated with Col I reside in patients with chronic atrial fibrillation. The upregulation of PDGF-BB,PDGFR-ββ,α-SMA gene expression may have contributed to the atrial structural remodeling during AF through enhanced collagen anabolic metabolism. PDGF and PDGFR play an important role through the activation of fibroblast.