This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kuoppala, A. Articles by Lindstedt, K. A. Search for Related Content PubMed PubMed Citation Articles by Kuoppala, A. Articles by Lindstedt, K. A.

CLINICAL STUDY

Down-regulation of cardioprotective bradykinin type-2 receptors in the left ventricle of patients with end-stage heart failure

Antti Kuoppala, MD^*, Naotaka Shiota, MD, PhD^*, Jorma O. Kokkonen, MD, PhD^*, Inka Liesmaa, MD^*, Karam Kostner, MD, PhD, Mikko Mäyränpää, MD^*, Petri T. Kovanen, MD, PhD^* and Ken A. Lindstedt, PhD^*,*

^* Wihuri Research Institute, Helsinki, Finland
Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland
Division of Cardiology, Allegemeines Krankenhaus, Vienna, Austria

Manuscript received September 20, 2001; revised manuscript received March 25, 2002, accepted April 5, 2002.

^* Reprint requests and correspondence: Dr. Ken A. Lindstedt, Wihuri Research Institute, Kalliolinnantie 4, FIN-00140 Helsinki, Finland.
ken.lindstedt{at}wri.fi

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.

Abbreviations and Acronyms   ACE   angiotensin-converting enzyme   AT-1R   angiotensin II type 1 receptor   AT-2R   angiotensin II type 2 receptor   BK   bradykinin   BK-2R   bradykinin type-2 receptor   CHD   coronary heart disease   DNA   deoxyribonucleic acid   eNOS   endothelial nitric oxide synthase   GAPDH   glyceraldehyde-3-phosphate dehydrogenase   HCAEC   human coronary artery endothelial cell   HF   heart failure   IDC   idiopathic dilated cardiomyopathy   LVH   left ventricular hypertrophy   PCR   polymerase chain reaction   RNA   ribonucleic acid   RT-PCR   reverse-transcriptase polymerase chain reaction

This article has been cited by other articles:

				S. Helske, M. Laine, M. Kupari, J. Lommi, H. Turto, L. Nurmi, I. Tikkanen, K. Werkkala, K. A. Lindstedt, and P. T. Kovanen Increased expression of profibrotic neutral endopeptidase and bradykinin type 1 receptors in stenotic aortic valves Eur. Heart J., August 1, 2007; 28(15): 1894 - 1903. [Abstract] [Full Text] [PDF]

				K. B. Keller and L. Lemberg Statin Therapy in Congestive Heart Failure Am. J. Crit. Care., July 1, 2005; 14(4): 338 - 340. [Full Text] [PDF]

				I. Liesmaa, A. Kuoppala, N. Shiota, J. O. Kokkonen, K. Kostner, M. Mayranpaa, P. T. Kovanen, and K. A. Lindstedt Increased expression of bradykinin type-1 receptors in endothelium of intramyocardial coronary vessels in human failing hearts Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2317 - H2322. [Abstract] [Full Text] [PDF]

				L. M. F. Leeb-Lundberg, F. Marceau, W. Muller-Esterl, D. J. Pettibone, and B. L. Zuraw International Union of Pharmacology. XLV. Classification of the Kinin Receptor Family: from Molecular Mechanisms to Pathophysiological Consequences Pharmacol. Rev., March 1, 2005; 57(1): 27 - 77. [Abstract] [Full Text] [PDF]