Cardiac electrical activity in a genomically "humanized" chromogranin a monogenic mouse model with hyperadrenergic hypertension.
J Cardiovasc Transl Res
; 7(5): 483-493, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24821335
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Arritmias Cardíacas
/
Cromogranina A
/
Sistema de Conducción Cardíaco
/
Hipertensión
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Cardiovasc Transl Res
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos