Congestive heart failure and expression of myocardial urotensin II.
BACKGROUND
Human urotensin II has several cardiovascular actions, including potent vasoactive, and cardiac inotropic and hypertropic properties. Our aim was to ascertain degree of expression of urotensin II and its receptor GPR14 (now known as UT receptor) in the myocardium of patients with congestive heart failure (CHF).


METHODS
We obtained specimens of myocardium from the hearts of 19 patients with end-stage CHF (12 ischaemic heart disease, seven dilated cardiomyopathy), five patients with early-stage CHF, and eight healthy controls. We used immunohistochemistry, in-situ hybridisation, reverse transcriptase-PCR (RT-PCR), and fluorescein isothiocyanate (FITC)-conjugated urotensin II to ascertain degree of myocardial expression of urotensin II and binding urotensin receptor.


RESULTS
Our results showed strong expression of urotensin II in the cardiomyocytes, and to a lesser extent in the vascular smooth muscle cells, endothelial cells, and inflammatory cells of patients with end-stage CHF. There was significantly less urotensin II expression in the myocardium of patients with early-stage CHF (p<0.0001). Also, there was little to no urotensin II expression in the myocardium of healthy controls. Myocardial expression of urotensin II correlated significantly with left ventricular end-diastolic dimension (p=0.0092), and inversely with ejection fraction (p=0.0002). RT-PCR showed increased concentrations of urotensin II and presence of urotensin receptor mRNA in the myocardium of patients with CHF. The confocal microscopy results showed a significant increase in the binding sites for urotensin in the myocardium of patients with end-stage CHF (p<0.0001).


CONCLUSIONS
Our findings suggest a possible role for urotensin II in the cardiac dysfunction and remodelling characteristic of CHF.
Douglas
Stephen A
SA
Cardiovascular and Urogenital Center of Excellence for Drug Discovery, GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
Tayara
Lara
L
Ohlstein
Eliot H
EH
Halawa
Nadine
N
Giaid
Adel
A
D000328:Adult; D000704:Analysis of Variance; D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000473:pathology; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D006439:Hemodynamics; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014579:Urotensins / Q000302:isolation & purification* / Q000378:metabolism
D005456:Fluorescent Dyes; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C029677:urotensin II; D016650:Fluorescein-5-isothiocyanate