Increased expression of bradykinin type-1 receptors in endothelium of intramyocardial coronary vessels in human failing hearts.
In experimental animals, bradykinin type-1 receptors (BK-1Rs) are induced during inflammation and ischemia, and, by exerting either cardioprotective or cardiotoxic effects, they may contribute to the pathogenesis of heart failure. Nothing is known about the expression of BK-1Rs in human heart failure. Human heart tissue was obtained from excised hearts of patients undergoing cardiac transplantation (n = 13), due to idiopathic dilated cardiomyopathy (IDC; n = 7) or to coronary heart disease (CHD; n = 6), and from normal hearts (n = 6). The expression of BK-1Rs was analyzed by means of competitive RT-PCR, Western blot analysis, and immunohistochemistry. Expression of BK-1R mRNA was increased in both IDC (2.8-fold) and CHD (2.1-fold) hearts compared with normal hearts. The observed changes were verified at the protein level. Expression of BK-1Rs in failing hearts localized to the endothelium of intramyocardial coronary vessels and correlated with an increased expression of TNF-alpha in the vessel wall. Treatment of human coronary artery endothelial cells with TNF-alpha increases their BK-1R expression. These novel results show that BK-1Rs are induced in the endothelium of intramyocardial coronary vessels in failing human hearts and so may participate in the pathogenesis of heart failure.
Liesmaa
Inka
I
Wihuri Research Institute, Helsinki, Finland.
Kuoppala
Antti
A
Shiota
Naotaka
N
Kokkonen
Jorma O
JO
Kostner
Karam
K
Mäyränpää
Mikko
M
Kovanen
Petri T
PT
Lindstedt
Ken A
KA
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology; D003327:Coronary Disease / Q000503:physiopathology; D003331:Coronary Vessels / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D043783:Receptor, Bradykinin B1 / Q000235:genetics*; D043782:Receptor, Bradykinin B2 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D014409:Tumor Necrosis Factor-alpha