A novel gene (Cmya3) induced in the heart by angiotensin II-dependent but not salt-dependent hypertension in mice.
OBJECTIVE
In previous studies using serial analysis of gene expression for elucidation of the molecular pathways of angiotensin II (Ang II)-induced hypertensive/ischemic cardiomyopathy in mice, we found that a hitherto unknown transcript, designated initially as 2310008C07Rik, an unknown expressed sequence tag (EST), was highly significantly upregulated in myocardial tissue. The current experiments were designed to further characterize this gene and to evaluate its expression in various types of hypertension.


METHODS
Mice rendered hypertensive by Ang II infused intravenously at 30 ng/min for 6 h or by osmotic minipump at 0.9 mug/h for 7 or 14 days, were compared to saline-infused normotensive controls and to mice with hypertension induced by subtotal nephrectomy and 1% saline as drinking water. At end point, mice were euthanized, their tissues processed for gene expression analysis, and results were confirmed by ribonuclease protection assay.


RESULTS
The Ang II-infused mice developed systolic blood pressure (BP) of 134 +/- 7, 158 +/- 13, and 149 +/- 15 mm Hg at 6 h, 7 days, and 14 days, respectively, compared to 102 +/- 9, 110 +/- 8, and 114 +/- 7 mm Hg in their respective controls and subtotally nephrectomized salt-fed mice had end point blood pressure of 153 +/- 5 v 112 +/- 7 mm Hg in controls. Through sequencing and expression analysis we found that the unknown transcript is part of the cardiomyopathy associated 3 (Cmya3) gene, being overexpressed in Ang II-induced but not salt-induced hypertension.


CONCLUSIONS
The highly expressed 2310008C07Rik EST was found to be part of Cmya3 and its upregulation is due to Ang II-induced myocardial damage and not to BP elevation per se.
Duka
Arvi
A
Department of Medicine, Hypertension and Atherosclerosis Section, Boston University School of Medicine, Boston, Massachusetts, USA.
Schwartz
Faina
F
Duka
Irena
I
Johns
Conrado
C
Melista
Efthymia
E
Gavras
Irene
I
Gavras
Haralambos
H
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001483:Base Sequence; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism; D015870:Gene Expression; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012965:Sodium Chloride
D000804:Angiotensin II; D012965:Sodium Chloride