Structural Remodeling And Expression Of Angiotensin II Receptor Subtypes In Human Left And Right Atrial Tissue In Atrial Fibrillation

Objective:To examine the change of structural remodeling and expression of angiotensin II receptor subtypes in human left and right atrial tissue in atrial fibrillation underlying heart valve disease. To investigate the mechanisms of Renin-Angiotensin System in the process of myocardial remodeling caused by atrial fibrillation.Methods:Left atrial (LA) and right atrial (RA) tissue samples were obtained from patients with AF or SR with underlying mitral valve disease and rheumatic heart disease during open heart surgery. Total 39 patients were enrolled, 25 with chronic atrial fibrillation and 14 with sinus rhythm. For each sample, histological examination was performed with routine hematoxylin/eosin and masson staining. We also used histological assessment software to calculate extracellular collagen matrix surface area fraction and quantify the amount of extracellular collagen matrix. AT1 and AT2 mRNA levels were measured by semi-quantitative reverse transcription polymerase chain reaction techniques. AT1 and AT2 protein levels were measured by immunohistochemistry techniques.Results:Compared with SR group, Left atrial inner diameter was significantly increased in the patients of the AF group .And there were no significant differences in left and right ventricular inner diameters, right atrial inner diameter, ejection fraction and pulmonary arterial pressure. In the histological examinations, myocardial hypertrophy, severe myolysis and extensive fibrosis in the interstitial space of the atria were found in AF group. And masson stain showed that mean extracellular collagen matrix surface area fraction was also significantly higher in either RA or LA of AF group. (p<0.05). The AT1 mRNA and protein levels in the LA significantly increased in patients with AF compared with SR (p < 0.05), whereas AT2 mRNA and protein were not significantly altered. And investigations of Ang II receptor subtypes' mRNA and protein levels in the RA did not exhibit any significant changes either in AT1 or AT2 in patients with AF versus SR. Conclusions:Chronic atrial fibrillation results in significant pathological alterations in atrial geometry, extracellular matrix and myocytes. Atrial structural remodeling in the artia of patient with AF is characterized by extensive atrial interstitial fibrosis, especially in LA. Atrial structural remodeling may help to promote AF initiation and maintenance. Renin-Angiotensin System AF is involved in the process of atrial structural remodeling. AF is associated with an up-regulation of AT1 in LA, and did not appear to influence the AT2 expression in the atrium. This may indicate a possible pathophysiologic role for Ang II and AT1 in AF. The molecular mechanisms involved in the process of atrial structural remodeling probably are series effects mediated by Ang II -AT1 activation.