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

作者：Gratze Petra; Dechend Ralf; Stocker Carolin; Park Joon Keun; Feldt Sandra; Shagdarsuren Erdenechimeg; Wellner Maren; Gueler Faikah; Rong Song; Gross Volkmar; Obst Michael; Plehm Ralph; Alenina Natalia; Zenclussen Ana; Titze Jens; Small Kersten; Yokota Yoshifumi; Zenke Martin; Luft Friedrich C; Muller Dominik N^*

来源：Circulation, 2008, 117(20): 2645-2656.

DOI：10.1161/CIRCULATIONAHA.107.760116

• hypertension
• angiotensin
• immune system
• kidney
• vasoconstriction

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.

• 出版日期2008-5-20
• 单位河北医科大学