title: Long-standing arterial hypertension is associated with Pitx2 down-regulation in a rat model of spontaneous atrial tachyarrhythmias.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Physiology Department, University of Medicine and Pharmacy of Tîrgu Mureş, Tîrgu Mureş 540139, Romania Unité de Neurocardiologie, EA 4612, Université Lyon 1, Lyon F-69008, France.
authors.forename: Alina
authors.initials: A
authors.lastname: Scridon
authors.affiliation: Unité 1060 INSERM CarMen, Université Lyon 1, Lyon F-69008, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Fouilloux-Meugnier
authors.affiliation: Unité 1060 INSERM CarMen, Université Lyon 1, Lyon F-69008, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Loizon
authors.affiliation: Unité 1060 INSERM CarMen, Université Lyon 1, Lyon F-69008, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Rome
authors.affiliation: Unité de Neurocardiologie, EA 4612, Université Lyon 1, Lyon F-69008, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Julien
authors.affiliation: Unité de Neurocardiologie, EA 4612, Université Lyon 1, Lyon F-69008, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Barrès
authors.affiliation: Unité de Neurocardiologie, EA 4612, Université Lyon 1, Lyon F-69008, France Service de Rythmologie, Hospices Civils de Lyon, Hôpital Louis Pradel, 28 Avenue du Doyen Lépine, Bron Cedex 69500, France philippe.chevalier@chu-lyon.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chevalier
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology* / Q000378:metabolism*; D002908:Chronic Disease; D015536:Down-Regulation; D018398:Homeodomain Proteins / Q000378:metabolism*; D006973:Hypertension / Q000150:complications* / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014157:Transcription Factors / Q000378:metabolism*; D000097577:Homeobox Protein PITX2
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2
keywords: Atrial tachyarrhythmia; Experimental model; Hypertension; Pitx2; Transcriptomics