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Novel role for the potent endogenous inotrope apelin in human cardiac dysfunction
- Source :
- Circulation. 108(12)
- Publication Year :
- 2003
-
Abstract
- Background— Apelin is among the most potent stimulators of cardiac contractility known. However, no physiological or pathological role for apelin–angiotensin receptor-like 1 (APJ) signaling has ever been described. Methods and Results— We performed transcriptional profiling using a spotted cDNA microarray with 12 814 unique clones on paired samples of left ventricle obtained before and after placement of a left ventricular assist device in 11 patients. The significance analysis of microarrays and a novel rank consistency score designed to exploit the paired structure of the data confirmed that natriuretic peptides were among the most significantly downregulated genes after offloading. The most significantly upregulated gene was the G-protein–coupled receptor APJ, the specific receptor for apelin. We demonstrate here using immunoassay and immunohistochemical techniques that apelin is localized primarily in the endothelium of the coronary arteries and is found at a higher concentration in cardiac tissue after mechanical offloading. These findings imply an important paracrine signaling pathway in the heart. We additionally extend the clinical significance of this work by reporting for the first time circulating human apelin levels and demonstrating increases in the plasma level of apelin in patients with left ventricular dysfunction. Conclusions— The apelin-APJ signaling pathway emerges as an important novel mediator of cardiovascular control.
- Subjects :
- Inotrope
Adult
Male
medicine.medical_specialty
Microarray
Adolescent
Receptors, G-Protein-Coupled
Contractility
Ventricular Dysfunction, Left
Predictive Value of Tests
Physiology (medical)
Internal medicine
Paracrine Communication
medicine
Cluster Analysis
Humans
Receptor
Apelin receptor
Oligonucleotide Array Sequence Analysis
Heart Failure
Apelin Receptors
business.industry
Receptors, Dopamine D2
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
Myocardium
Middle Aged
Coronary Vessels
Myocardial Contraction
Apelin
Gene expression profiling
Endocrinology
Gene Expression Regulation
Significance analysis of microarrays
Disease Progression
Intercellular Signaling Peptides and Proteins
Heart-Assist Devices
Cardiology and Cardiovascular Medicine
business
Carrier Proteins
Biomarkers
Subjects
Details
- ISSN :
- 15244539
- Volume :
- 108
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Circulation
- Accession number :
- edsair.doi.dedup.....fde8af3491697b480b67af810e90db3a