Novel role for inhibitor of differentiation 2 in the genesis of angiotensin II-induced hypertension

Tools

Item Type:	Article
Title:	Novel role for inhibitor of differentiation 2 in the genesis of angiotensin II-induced hypertension
Creators Name:	Gratze, P., Dechend, R., Stocker, C., Park, J.K., Feldt, S., Shagdarsuren, E., Wellner, M., Gueler, F., Rong, S., Gross, V., Obst, M., Plehm, R., Alenina, N., Zenclussen, A., Titze, J., Small, K., Yokota, Y., Zenke, M., Luft, F.C. and Mueller, D.N.
Abstract:	BACKGROUND: -Angiotensin (Ang) II-induced target-organ damage involves innate and acquired immunity. Mice deficient for the helix-loop-helix transcription factor inhibitor of differentiation (Id2(-/-)) lack Langerhans and splenic CD8a+ dendritic cells, have reduced natural killer cells, and have altered CD8 T-cell memory. We tested the hypothesis that an alteration in the number and quality of circulating blood cells caused by Id2 deletion would ameliorate Ang II-induced target-organ damage. Methods and Results-We used gene-deleted and transgenic mice. We conducted kidney and bone marrow transplants. In contrast to Ang II-infused Id2(+/-), Id2(-/-) mice infused with Ang II remained normotensive and failed to develop albuminuria or renal damage. Bone marrow transplant of Id2(+/-) bone marrow to Id2(-/-) mice did not restore the blunted blood pressure response to Ang II. Transplantation of Id2(-/-) kidneys to Id2(+/-) mice also could not prevent Ang II-induced hypertension and renal damage. We verified the Ang II resistance in Id2(-/-) mice in a model of local tissue Ang II production by crossing hypertensive mice transgenic for rat angiotensinogen with Id2(-/-) or Id2(+/-) mice. Angiotensinogen-transgenic Id2(+/-) mice developed hypertension, albuminuria, and renal injury, whereas angiotensinogen-transgenic Id2(-/-) mice did not. We also found that vascular smooth muscle cells from Id2(-/-) mice showed an antisenescence phenotype. Conclusions-Our bone marrow and kidney transplant experiments suggest that alterations in circulating immune cells or Id2 in the kidney are not responsible for Ang II resistance. The present studies identify a previously undefined role for Id2 in the pathogenesis of Ang II-induced hypertension.
Keywords:	Hypertension, Angiotensin, Immune System, Kidney, Vasoconstriction, Animals, Mice
Source:	Circulation
ISSN:	0009-7322
Publisher:	American Heart Association
Volume:	117
Number:	20
Page Range:	2645-2656
Date:	20 May 2008
Official Publication:	https://doi.org/10.1161/CIRCULATIONAHA.107.760116
PubMed:	View item in PubMed

Repository Staff Only: item control page