Modulation of Kinin B2 Receptor Signaling Controls Aortic Dilatation and Rupture in the Angiotensin II-Infused Apolipoprotein E-Deficient Mouse.
Arterioscler Thromb Vasc Biol
; 36(5): 898-907, 2016 05.
Article
en En
| MEDLINE
| ID: mdl-26966276
ABSTRACT
OBJECTIVE:
Abdominal aortic aneurysm (AAA) is an important cause of mortality in older adults. Activity of the local kallikrein-kinin system may be important in cardiovascular disease. The effect of kinin B2 receptor (B2R) agonist and antagonist peptides on experimental AAA was investigated. APPROACH ANDRESULTS:
AAA was induced in apolipoprotein E-deficient mice via infusion of angiotensin II (1.0 µg/kg per minute SC). B2R agonists or antagonists were given via injection (2 mg/kg IP) every other day. The B2R agonist (B9772) promoted aortic rupture in response to angiotensin II associated with an increase in neutrophil infiltration of the aorta in comparison to controls. Mice receiving a B2R/kinin B1 receptor antagonist (B9430) were relatively protected from aortic rupture. Neutrophil depletion abrogated the ability of the B2R agonist to promote aortic rupture. Progression of angiotensin II-induced aortic dilatation was inhibited in mice receiving a B2R antagonist (B9330). Secretion of metalloproteinase-2 and -9, osteoprotegerin, and osteopontin by human AAA explant was reduced in the presence of the B2R antagonist (B9330). B2R agonist and antagonist peptides enhanced and inhibited, respectively, angiotensin II-induced neutrophil activation and aortic smooth muscle cell inflammatory phenotype. The B2R antagonist (B9330; 5 µg) delivered directly to the aortic wall 1 week post-AAA induction with calcium phosphate in a rat model reduced aneurysm growth associated with downregulation of aortic metalloproteinase-9.CONCLUSIONS:
B2R signaling promotes aortic rupture within a mouse model associated with the ability to stimulate inflammatory phenotypes of neutrophils and vascular smooth muscle cells. B2R antagonism could be a potential therapy for AAA.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
/
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
1_doencas_nao_transmissiveis
/
6_cardiovascular_diseases
Asunto principal:
Aorta Abdominal
/
Rotura de la Aorta
/
Apolipoproteínas E
/
Angiotensina II
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Aneurisma de la Aorta Abdominal
/
Receptor de Bradiquinina B2
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Asunto de la revista:
ANGIOLOGIA
Año:
2016
Tipo del documento:
Article