The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
[Pyr 1 ]Apelin-13 Identified as the Predominant Apelin Isoform in the Human Heart: Vasoactive Mechanisms and Inotropic Action in Disease
Abstract
Apelin receptors, present on vascular smooth muscle cells, endothelium, and cardiomyocytes, are activated by the family of apelin peptides to elicit cardiovascular effects in experimental animals, but functional activity in humans has not been studied in detail. We detected low levels of apelin immunoreactivity in plasma of volunteers consistent with an autocrine/paracrine action and detected apelin immunoreactivity in the supernatant from human cultured endothelial cells. We found that [Pyr 1 ]apelin-13 was the predominant isoform in cardiac tissue from patients with coronary artery disease. We tested the hypothesis that apelins have vascular and cardiac actions in human tissues in vitro and compared responses to [Pyr 1 ]apelin-13, apelin-13, and apelin-36. In endothelium-intact mammary artery, all 3 of the apelins induced concentration-dependent vasodilatation with comparable potency (EC 50 : 0.6 to 1.6 nM; maximum response: 40% to 50%). Vasodilatation was abolished after endothelial removal or preincubation with indomethacin but was unaffected by preincubation with N G -nitro- l -arginine methyl ester, indicating involvement of prostanoids but not NO in dilatation by apelins in this patient group. Apelins were potent constrictors of endothelium-denuded saphenous vein (EC 50 : 0.6 to 1.6 nM; maximum response: 17% to 26%) and mammary artery ([Pyr 1 ]apelin-13; EC 50 : 0.2 nM; maximum response: 29%). In paced atrial strips, all 3 of the peptides increased the force of contraction with subnanomolar potencies (EC 50 : 40 to 125 pM). For the first time, we demonstrate that the 3 principal forms of apelin have comparable potency and efficacy in human cardiovascular tissues. Apelins are potent endothelium-dependent vasodilators acting via a prostanoid-dependent mechanism; however, removal of the endothelium revealed direct vasoconstrictor actions in both the artery and vein. Furthermore, in human cardiac tissue, the apelin peptides are among the most potent endogenous positive inotropic agents yet reported.
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Citations
Cites
Isolation and Characterization of a Novel Endogenous Peptide Ligand for the Human APJ Receptor
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Cited by
Davenport, A. P., Hyndman, K. A., Dhaun, N., Southan, C., Kohan, D. E., Pollock, J. S., Pollock, D. M., Webb, D. J., & Maguire, J. J. (2016) · Pharmacological Reviews · doi:10.1124/pr.115.011833 · Cited by 772
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Targeting the apelin system for the treatment of cardiovascular diseases
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“59,60 In contrast, several studies do report a vasoconstrictor action of both central and peripherally administered apelin in vitro and in vivo however these involve different animal species and different vascular beds.”
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Metadata
- Authors
- Maguire, J. J., Kleinz, M. J., Pitkin, S. L., & Davenport, A. P.
- Venue
- Hypertension
- Published
- 2009-09
- Volume
- 54
- Issue
- 3
- Pages
- 598-604
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2132493114
- Cited by
- 323
- References
- 44
- FWCI
- 7.90
- Type
- journal article
- Language
- en
- Open access
- closed
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- Maguire, J. J., Kleinz, M. J., Pitkin, S. L., & Davenport, A. P. (2009). [Pyr 1 ]Apelin-13 Identified as the Predominant Apelin Isoform in the Human Heart: Vasoactive Mechanisms and Inotropic Action in Disease. Hypertension. https://doi.org/10.1161/hypertensionaha.109.134619
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