Predisposition to atherosclerosis and aortic aneurysms in mice deficient in kinin B1 receptor and apolipoprotein E.

Vanessa F. Merino, Mihail Todiras, Marcelo A. Mori, Vicência M.T. Sales, Raphael G. Fonseca, Vera Saul, Katja Tenner, Michael Bader, João B. Pesquero

Research output: Contribution to journalArticle

Abstract

Kinin B1 receptor is involved in chronic inflammation and expressed in human atherosclerotic lesions. However, its significance for lesion development is unknown. Therefore, we investigated the effect of kinin B1 receptor deletion on the development of atherosclerosis and aortic aneurysms in apolipoprotein E-deficient (ApoE(-/-)) mice. Mice deficient both in ApoE and in kinin B1 receptor (ApoE(-/-)-B(1)(-/-)) were generated and analyzed for their susceptibility to atherosclerosis and aneurysm development under cholesterol rich-diet (western diet) and angiotensin II infusion. Kinin B1 receptor messenger RNA (mRNA) expression was significantly increased in ApoE(-/-) mice after Western-type diet. Although no difference in serum cholesterol was found between ApoE(-/-)-B(1)(-/-) and ApoE(-/-) mice under Western-type diet, aortic lesion incidence was significantly higher in ApoE(-/-)-B(1)(-/-) after this treatment. In accordance, we observed increased endothelial dysfunction in these mice. The mRNA expression of cyclic guanosine monophosphate-dependent protein kinase I, CD-11, F4/80, macrophage colony-stimulating factor, and tumor necrosis factor-alpha were increased in the aorta of double-deficient mice following Western-type diet, whereas the levels of peroxisome proliferator-activated receptor gamma protein and the activity of matrix metalloproteinase-9 activity were decreased. In addition to the increased atherosclerotic lesions, the lack of kinin B(1) receptor also increased the incidence of abdominal aortic aneurysms after angiotensin II infusion. In conclusion, our results show that kinin B(1) receptor deficiency aggravates atherosclerosis and aortic aneurysms under cholesterolemic conditions, supporting an antiatherogenic role for the kinin B(1) receptor.

Original languageEnglish (US)
Pages (from-to)953-963
Number of pages11
JournalJournal of molecular medicine (Berlin, Germany)
Volume87
Issue number10
DOIs
StatePublished - Oct 2009
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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