title: Novel role for inhibitor of differentiation 2 in the genesis of angiotensin II-induced hypertension.
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.
  
  
  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.
authors.affiliation: Medical Faculty of the Charité, Experimental and Clinical Research Center, Franz Volhard Clinic, Berlin, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Gratze
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.forename: Carolin
authors.initials: C
authors.lastname: Stocker
authors.forename: Joon-Keun
authors.initials: JK
authors.lastname: Park
authors.forename: Sandra
authors.initials: S
authors.lastname: Feldt
authors.forename: Erdenechimeg
authors.initials: E
authors.lastname: Shagdarsuren
authors.forename: Maren
authors.initials: M
authors.lastname: Wellner
authors.forename: Faikah
authors.initials: F
authors.lastname: Gueler
authors.forename: Song
authors.initials: S
authors.lastname: Rong
authors.forename: Volkmar
authors.initials: V
authors.lastname: Gross
authors.forename: Michael
authors.initials: M
authors.lastname: Obst
authors.forename: Ralph
authors.initials: R
authors.lastname: Plehm
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
authors.forename: Ana
authors.initials: A
authors.lastname: Zenclussen
authors.forename: Jens
authors.initials: J
authors.lastname: Titze
authors.forename: Kersten
authors.initials: K
authors.lastname: Small
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Yokota
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Dominik N
authors.initials: DN
authors.lastname: Muller
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001773:Blood Cells / Q000276:immunology; D016026:Bone Marrow Transplantation; D006973:Hypertension / Q000139:chemically induced / Q000209:etiology*; D007107:Immune System / Q000166:cytology; D051797:Inhibitor of Differentiation Protein 2 / Q000172:deficiency / Q000502:physiology*; D016030:Kidney Transplantation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
chemical_list: D051797:Inhibitor of Differentiation Protein 2; D000804:Angiotensin II