title: [Early atrial gene regulation of obesity-related arterial hypertension].
abstract: High fat diet (HFD) induces both arterial hypertension and tachycardia in dogs. Changes in heart rate occur early and are in part due to a decrease in the parasympathetic drive to the heart secondary to down-regulation of atrial muscarinic M2 receptors (Pelat et al. Hypertension 1999; 340: 1066-72). These data suggest that HFD is able to modify genic expression at atrial level. Thus, the aim of this work was to perform a systematic study of the genic expression profile in dogs made obese and hypertensive by 9 weeks of HFD. Blood pressure and heart rate were measured by telemetry implanted 15 days before starting regimen in 6 HFD and in 6 control dogs. HFD was the normal canine diet administered to controls but mixed with 300 g of beef fat. At the end of the experience, animals were sacrified and right atria were collected. Gene regulation was assessed in pooled tissue samples from both groups using suppressive substractive hybridization and microarray analysis. Genes with induction or repression rates of at least 20% when compared to controls were sequenced. As previously reported HFD induced a significant increase in body weight, blood pressure and heart rate when compared to controls. The results of SSH experiments led to the identification of 32 genes which are differentially regulated in atria from HFD dogs. Most are genes encoding proteins which have been previously shown to be regulated during various cardiopathies (MMP9, Na/K-ATPase 3...). These changes indicate the existence of early remodeling processes of atrial myocardium secondary to HFD. Other group of genes encodes proteins with no role identified in heart up today (lec-3, ERK-3, TRIP1, nucleophosmin...) or which function remains totally unknown. This work confirms that HFD is associated with early changes in gene expression in atrium. These changes are unlikely to be related to ventricular hypertrophy which is observed only during long-term HFD. Further studies are necessary to demonstrate the role of these modifications in the pathophysiological mechanisms leading to the increase in heart rate in this model of obesity-related arterial hypertension.
mesh_terms: D000818:Animals; D016275:Atrial Function; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D004041:Dietary Fats; D004285:Dogs; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006339:Heart Rate / Q000235:genetics / Q000502:physiology; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology / Q000662:veterinary; D008297:Male; D009765:Obesity / Q000150:complications* / Q000235:genetics / Q000662:veterinary
chemical_list: D004041:Dietary Fats
vernacular_title: Modifications précoces du transcriptome auriculaire dans l'hypertension artérielle associée à l'obésité chez le chien.