Long-standing arterial hypertension is associated with Pitx2 down-regulation in a rat model of spontaneous atrial tachyarrhythmias

• Published in: Europace (London, England) England), 2015-01, Vol.17 (1), p.160-165
• Main Authors: Scridon, Alina, Fouilloux-Meugnier, Emmanuelle, Loizon, Emmanuelle, Rome, Sophie, Julien, Claude, Barrès, Christian, Chevalier, Philippe
• Format: Article
• Language: English
• Subjects: Aging - metabolism; Animals; Atrial Fibrillation - etiology; Atrial Fibrillation - metabolism; Cardiology and cardiovascular system; Chronic Disease; Down-Regulation; Homeobox Protein PITX2; Homeodomain Proteins - metabolism; Human health and pathology; Hypertension - complications; Hypertension - metabolism; Life Sciences; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Transcription Factors - metabolism
• ISSN: 1099-5129; 1532-2092
• DOI: 10.1093/europace/euu139

The timecourse of left atrial Pitx2 down-regulation in the setting of atrial tachyarrhythmias remains unknown. Accordingly, we aimed to assess the age dependency of left atrial Pitx2 expression in an experimental model of spontaneous atrial tachyarrhythmias in rats. Atrial sampling was performed in three groups (n = 4 each) of young (14-week-old), adult (24-week-old), and ageing (48-week-old) spontaneously hypertensive rats (SHRs), in which we previously demonstrated the age dependency of spontaneous atrial tachyarrhythmias, and three groups (n = 4 each) of age-matched normotensive Wistar-Kyoto (WKY) rats. mRNA expression of Pitx2 was studied using real-time polymerase chain reaction. Ageing SHRs presented significantly lower left atrial Pitx2 expressions compared with age-matched WKY rats (P = 0.02), while no significant difference was observed between young or adult SHRs and age-matched WKY rats (both P > 0.05). Among SHRs, Pitx2 expressions showed a progressive, age-dependent decrease (34.9 ± 6.7 in young SHRs, 17.1 ± 3.6 in adult SHRs, and 10.7 ± 1.7 in ageing SHRs, P = 0.04) and were significantly negatively correlated with both age (Spearman r = -0.86, P < 0.01) and heart weight (Spearman r = -0.76, P < 0.01). The present study suggests the presence of age-dependent left atrial Pitx2 down-regulation in SHRs. The strong negative correlation between left atrial Pitx2 expression and heart weight among SHRs may indicate a link between long-standing arterial hypertension and Pitx2-related atrial arrhythmogenicity.