K4 Elite
K4 Elite
An endogenous heptapeptide of the renin-angiotensin system generated largely by ACE2, studied as the Mas receptor ligand forming the counter-regulatory arm to the ACE/angiotensin II/AT1 pathway.
Angiotensin-(1-7) is a naturally occurring heptapeptide, Asp-Arg-Val-Tyr-Ile-His-Pro, formed principally by angiotensin-converting enzyme 2 (ACE2) cleaving a single residue from angiotensin II, and by other routes from angiotensin I [1].
Its place in the literature is defined by contrast: the classical renin-angiotensin arm runs ACE to angiotensin II to the AT1 receptor and is associated with vasoconstriction and proliferative signaling, while the ACE2/Ang-(1-7)/Mas axis is described as the counter-regulatory arm with largely opposing actions [1][4].
It is among the most heavily studied peptides in cardiovascular physiology, with a dedicated Physiological Reviews monograph and a knockout-mouse literature that establishes receptor identity and physiological role [1][2].
The proto-oncogene product Mas is a class A G protein-coupled receptor identified as a receptor for Ang-(1-7) in 2003, when specific binding of the heptapeptide to Mas-transfected cells was demonstrated and shown to be abolished in kidney sections from Mas-deficient mice [1].
Downstream signaling reported in cardiomyocyte and vascular preparations includes nitric oxide release, activation of the PI3K/Akt/eNOS pathway, and inhibition of pathways associated with inflammation and cellular and vascular growth. Reports also describe interaction with AT2 and MrgD receptors, which is one reason receptor attribution in this literature is handled carefully [3][4].
Santos and colleagues examined heart function in Mas knockout mice. Localization of Mas in mouse heart was assessed by binding of rhodamine-labelled Ang-(1-7); cardiac function was measured in isolated heart preparations and confirmed by echocardiography. Mas-deficient animals were reported to show lower systolic tension (approximately 1.4 +/- 0.09 g versus 2.1 +/- 0.03 g in Mas+/+ littermates), together with lower dT/dt and heart rate [2].
Receptor-identification work in 2003 demonstrated specific binding of Ang-(1-7) to Mas-transfected cells and showed that this binding was absent in kidney sections from Mas-deficient mice, establishing Mas as a receptor for the heptapeptide [1].
Cardiomyocyte studies published in Hypertension dissected the intracellular pathways engaged by Ang-(1-7) via Mas, using isolated cardiomyocyte preparations and pathway inhibitors to map the signaling cascade [3].
Work in rats reported expression of the Ang-(1-7)/Mas receptor axis in sinoatrial node cells, using immunolocalization together with electrophysiological measures of pacemaker activity [6].
A Physiological Reviews monograph aggregates the enzymology, receptor pharmacology, knockout phenotypes and organ-system findings across the ACE2/Ang-(1-7)/MAS literature [1].
Combinations examined in the research literature. Descriptive only — not a recommendation to combine compounds.