Abstract
Matrix metalloproteinase (MMP) plays an important role in the pathogenesis of atrial fibrillation (AF). The MMP9 promoter has a functional polymorphism rs3918242 that can regulate the level of gene transcription. This study recruited 200 AF patients and 240 controls. The MMP9 rs3918242 was examined by polymerase chain reactions. HL-1 atrial myocytes were cultured and electrically stimulated. Right atrial appendages were obtained from six patients with AF and three controls with sinus rhythm undergoing open heart surgery. The MMP9 expression and activity were determined using immunohistochemical analysis and gelatin zymography, respectively. Rapid pacing induces MMP9 secretion from HL-1 myocytes in a time- and dose-dependent manner. The responsiveness of MMP9 transcriptional activity to tachypacing was significantly enhanced by rs3918242. The expression of MMP9 was increased in fibrillating atrial tissue than in sinus rhythm. However, the distribution of rs3918242 genotypes and allele frequencies did not significantly differ between the control and AF groups. HL-1 myocyte may secrete MMP9 in response to rapid pacing, and the secretion could be modulated by rs3918242. Although the MMP9 expression of human atrial myocyte is associated with AF, our study did not support the association of susceptibility to AF among Taiwanese subjects with the MMP9 rs3918242 polymorphism.
Highlights
IntroductionAtrial fibrillation (AF) is the most prevalent arrhythmia in clinical practice, affecting about 46.1 million people worldwide [1], and it is associated with increased morbidity (especially stroke [2] and heart failure [3]) and mortality [4]
Atrial fibrillation (AF) is the most prevalent arrhythmia in clinical practice, affecting about 46.1 million people worldwide [1], and it is associated with increased morbidity and mortality [4]
The present study aims to test if rapid pacing would induce MMP9 secretion by the atrial myocyte, and to elucidate the association between the MMP9 promoter gene polymorphism, the MMP9 expression in atrial tissue, and the risk of AF
Summary
Atrial fibrillation (AF) is the most prevalent arrhythmia in clinical practice, affecting about 46.1 million people worldwide [1], and it is associated with increased morbidity (especially stroke [2] and heart failure [3]) and mortality [4]. A prospective case-cohort study demonstrated that, in individuals free of AF initially, elevated plasma levels of MMP9 were independently associated with increased risk of AF during an 11.8 years follow-up period [13]. We have demonstrated that a single nucleotide polymorphism (SNP) rs3918242 in the promoter region of MMP9 gene is independently and significantly associated with plasma MMP9 level in a Taiwanese population [16]. Since “AF begets AF”, whether electrical remodeling of atrial myocyte will increase its MMP9 expression and propagate atrial interstitium ECM degradation with structural remodeling demands to be determined. The present study aims to test if rapid pacing would induce MMP9 secretion by the atrial myocyte, and to elucidate the association between the MMP9 promoter gene polymorphism, the MMP9 expression in atrial tissue, and the risk of AF
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