Novel role for retinol-binding protein 4 in the regulation of blood pressure

Bettina J. Kraus, Juliano L. Sartoretto, Pazit Polak, Tetsuya Hosooka, Takashi Shiroto, Iratxe Eskurza, Seung Ah Lee, Hongfeng Jiang, Thomas Michel, Barbara B. Kahn

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Elevated levels of serum retinol-binding protein 4 (RBP4) contribute to insulin resistance and correlate with increased prevalence of hypertension and myocardial infarction. We sought to determine whether lowering RBP4 would improve blood pressure (BP) and protect against obesity- or angiotensin (Ang)-II-induced hypertension. Systolic and diastolic BP were lower in the RBP4-knockout (RBP4-KO) mice and higher in the RBP4- overexpressing (RBP4-Tg) mice compared with BP in the wild-type (WT) littermates. Carbachol-induced vasodilatation was increased in arteries from the RBP4-KO compared with the WT mice and was impaired in the RBP4-Tg mice. Aortic eNOSSer1177 phosphorylation was enhanced ∼50%in theRBP4-KOmice, with no change in total eNOS protein. Feeding a high-fat diet increased BP in the RBP4- KOmice only to the level in theWTmice fed chow and had no effect on aortic eNOSSer1177 phosphorylation. Ang-II infusion resulted in 22 mmHg lower systolic BP in the RBP4-KO than in the WT mice, although the relative BP increase over saline infusion was ∼30% in both. Ang-II treatment decreased aortic eNOSSer1177 phosphorylation in the WT and RBP4-KO mice, but phosphorylation remained higher in the RBP4-KO mice. Cardiac hypertrophy with Ang-II treatment was diminished by 56% in the RBP4- KO mice. Thus, elevated serum RBP4 raises BP and lack of RBP4 reduces it, with commensurate changes in aortic eNOSSer1177 phosphorylation. Lowering RBP4 may reduce BP through enhanced eNOS-mediated vasodilatation and may be a novel therapeutic approach for hypertension.- Kraus,B. J., Sartoretto, J.L.,Polak,P.,Hosooka,T., Shiroto,T., Eskurza, I., Lee, S.-A., Jiang, H.,Michel, T., Kahn, B. B. Novel role for retinol-binding protein 4 in the regulation of blood pressure.

Original languageEnglish
Pages (from-to)3133-3140
Number of pages8
JournalFASEB Journal
Volume29
Issue number8
DOIs
Publication statusPublished - 2015 Aug 1
Externally publishedYes

Keywords

  • Angiotensin II
  • Endothelial no-synthase
  • Hypertension
  • Obesity

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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