Down-regulation of cardioprotective bradykinin type-2 receptors in the left ventricle of patients with end-stage heart failure.
J Am Coll Cardiol
; 40(1): 119-25, 2002 Jul 03.
Article
em En
| MEDLINE
| ID: mdl-12103265
ABSTRACT
OBJECTIVES:
We sought to study the expression of bradykinin type-2 receptors (BK-2Rs) in patients with heart failure (HF).BACKGROUND:
Recent work in experimental animals has suggested that bradykinin (BK) exerts cardioprotective effects through specific BK-2Rs. However, nothing is known about the regulation of BK-2R expression in the pathogenesis of human HF.METHODS:
Human heart tissue was obtained from excised hearts of patients undergoing cardiac transplantation (n = 13) and from normal hearts (n = 6) unsuitable for donation. The patients had HF due to idiopathic dilated cardiomyopathy (IDC) (n = 7) or coronary heart disease (CHD) (n = 6). Tissue samples from the left ventricles were analyzed by competitive reverse-transcriptase-polymerase chain reaction and Western blotting for the expression of BK-2R messenger ribonucleic acid (mRNA) and protein.RESULTS:
In both the IDC and CHD hearts, the level of BK-2R mRNA expression was found to be significantly lower (30% and 38% of control values, respectively) than that in normal hearts. Correspondingly, the BK-2R protein level was significantly reduced in both the IDC and CHD hearts (45% and 62% of control values, respectively) and apparently involved all myocardial cell types. The down-regulation of BK-2R expression in failing hearts did not correlate with decreased cellularity or with the expression pattern of other members of the G-protein-coupled receptor superfamily. However, BK-2R down-regulation in the failing hearts was associated with a decrease in endothelial nitric oxide synthase in both IDC (53% of control value) and CHD (43% of control value) hearts.CONCLUSIONS:
These results are the first to suggest that a loss of BK-2Rs is involved in the pathogenesis of human HF.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Função Ventricular Esquerda
/
Receptores da Bradicinina
/
Insuficiência Cardíaca
Tipo de estudo:
Etiology_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article