title: Cardiac electrical activity in a genomically "humanized" chromogranin a monogenic mouse model with hyperadrenergic hypertension.
abstract: The prohormone chromogranin A (CHGA) is ubiquitously found in vesicles of adrenal chromaffin cells and adrenergic neurons, and it is processed to the hypotensive hormone peptide catestatin (CST). Both CHGA and CST regulate blood pressure and cardiac function. This study addresses their role in cardiac electrical activity. We have generated two genomically "humanized" transgenic mouse strains (Tg31CHGA+/+; Chga-/- (HumCHGA31) and Tg19CHGA+/+; Chga-/- (HumCHGA19)) with varied CHGA expression and the ability to rescue the Chga-/- phenotype (hypertensive, hyperadrenergic with dilated cardiomyopathy). The normotensive HumCHGA31 mice express CHGA at levels comparable to wild-type. In contrast, the hypertensive HumCHGA19 mice have low levels of CHGA. EKG recordings revealed that the QT interval, R-amplitude, and QRS time-voltage integral are markedly longer in HumCHGA19 compared to wild-type and HumCHGA31 mice. These differences are accompanied by increased heart rate and QT variability, indicating that ventricular assault happens in a status of low levels of circulating CST.
authors.affiliation: Department of Medicine, University of California at San Diego, USA.
authors.forename: Nagendu B
authors.initials: NB
authors.lastname: Dev
authors.affiliation: Department of Medicine, University of California at San Diego, USA.
authors.forename: Saiful A
authors.initials: SA
authors.lastname: Mir
authors.affiliation: CSIR- Central Drug Research Institute, India.
authors.forename: Jiaur R
authors.initials: JR
authors.lastname: Gayen
authors.affiliation: Department of Medicine, University of California at San Diego, USA.
authors.forename: Jawed A
authors.initials: JA
authors.lastname: Siddiqui
authors.affiliation: Department of Medicine, University of California at San Diego, USA.
authors.forename: Maja
authors.initials: M
authors.lastname: Mustapic
authors.affiliation: Department of Medicine, University of California at San Diego, USA.
authors.forename: Sucheta M
authors.initials: SM
authors.lastname: Vaingankar
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D001794:Blood Pressure; D053379:Chromogranin A / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005838:Genotype; D006329:Heart Conduction System / Q000503:physiopathology*; D006339:Heart Rate; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000097:blood; D010641:Phenotype; D013997:Time Factors
chemical_list: C506150:CHGA protein, human; D053379:Chromogranin A; D010446:Peptide Fragments; C109084:chromogranin A (344-364); C506155:chromogranin A, mouse