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Alamandine

Peptide Discovered in Human Blood Circulation

Simplified action model of the renin-agiotensin sytem cascade

Difference of  Angiotensin-A (1-7) / Angiotensin-II ratio in the plasma from chronic renal failure (CRF) patients and healthy controls.

Lautner RQ  et al. Circ Res. 2013 Apr 12;112(8):1104-11.

 

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Discovery and characterization of alamandine: a novel component of the renin-angiotensin system.

RATIONALE:
The renin-angiotensin system (RAS) is a key regulator of the cardiovascular system, electrolyte, and water balance. Here, we report identification and characterization of alamandine, a new heptapeptide generated by catalytic action of angiotensin-converting enzyme-2 angiotensin A or directly from angiotensin-(1-7).

OBJECTIVE:
To characterize a novel component of the RAS, alamandine.

METHODS AND RESULTS:
Using mass spectrometry we observed that alamandine circulates in human blood and can be formed from angiotensin-(1-7) in the heart. Alamandine produces several physiological actions that resemble those produced by angiotensin-(1-7), including vasodilation, antifibrosis, antihypertensive, and central effects. Interestingly, our data reveal that its actions are independent of the known vasodilator receptors of the RAS, Mas, and angiotensin II type 2 receptor. Rather, we demonstrate that alamandine acts through the Mas-related G-protein-coupled receptor, member D. Binding of alamandine to Mas-related G-protein-coupled receptor, member D is blocked by D-Pro(7)-angiotensin-(1-7), the Mas-related G-protein-coupled receptor, member D ligand β-alanine and PD123319, but not by the Mas antagonist A-779. In addition, oral administration of an inclusion compound of alamandine/β-hydroxypropyl cyclodextrin produced a long-term antihypertensive effect in spontaneously hypertensive rats and antifibrotic effects in isoproterenol-treated rats. Alamandine had no noticeable proliferative or antiproliferative effect in human tumoral cell lines.

CONCLUSIONS:
The identification of these 2 novel components of the RAS, alamandine and its receptor, provides new insights for the understanding of the physiological and pathophysiological role of the RAS and may help to develop new therapeutic strategies for treating human cardiovascular diseases and other related disorders.

Lautner RQ, Villela DC, Fraga-Silva RA et al., Circ Res. 2013 Apr 12;112(8):1104-11. doi: 10.1161/CIRCRESAHA.113.301077. Epub 2013 Feb 27.

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The never-ending story of angiotensin peptides: beyond angiotensin I and II.

Dell'Italia LJ, Ferrario CM., Circ Res. 2013 Apr 12;112(8):1086-7. doi: 10.1161/CIRCRESAHA.113.301246.

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Cardiovascular effects of angiotensin A: A novel peptide of the renin-angiotensin system.

Coutinho DC, Foureaux G, Rodrigues KD, et al., J Renin Angiotensin Aldosterone Syst. 2013 Feb 5. [Epub ahead of print]

Click to Expand Mass-spectrometric identification of a novel angiotensin peptide in human plasma.

Jankowski V, Vanholder R, van der Giet M et al., Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):297-302. Epub 2006 Nov 30.

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