Angiotensin A/Alamandine/MrgD Axis: Another Clue to Understanding Cardiovascular Pathophysiology

Abstract

The renin-angiotensin system (RAS) plays a crucial role in cardiovascular regulations and its modulation is a challenging target for the vast majority of cardioprotective strategies. However, many biological effects of these drugs cannot be explained by the known mode of action. Our comprehension of the RAS is thus far from complete. The RAS represents an ingenious system of “checks and balances”. It incorporates vasoconstrictive, pro-proliferative, and pro-inflammatory compounds on one hand and molecules with opposing action on the other hand. The list of these molecules is still not definitive because new biological properties can be achieved by minor alteration of the molecular structure. The angiotensin A/alamandine-MrgD cascade associates the deleterious and protective branches of the RAS. Its identification provided a novel clue to the understanding of the RAS. Angiotensin A (Ang A) is positioned at the “crossroad” in this system since it either elicits direct vasoconstrictive and pro-proliferative actions or it is further metabolized to alamandine, triggering opposing effects. Alamandine, the central molecule of this cascade, can be generated both from the “deleterious” Ang A as well as from the “protective” angiotensin 1–7. This pathway modulates peripheral and central blood pressure regulation and cardiovascular remodeling. Further research will elucidate its interactions in cardiovascular pathophysiology and its possible therapeutic implications.

Nicotine and the renin-angiotensin system

“…In addition to the above components of the RAS, ANG II is further metabolized to ANG III by aminopeptidase A, which is then converted to ANG IV by aminopeptidase N (50). ANG II can also be converted to angiotensin A by mononuclear leukocyte-derived aspartate decarboxylase, leading to the formation of alamandine, which has been shown to bind to the Mas-related G proteincoupled receptor D (68).…”

Perspectives on the Potential Benefits of Antihypertensive Peptides towards Metabolic Syndrome

“…The most recent identified member of the vasodilatory axis of the RAS is alamandine. This heptapeptide is generated directly from Ang 1-7 through the action of descarboxylase ACE2 and acts upon MAS-related G-protein-coupled receptor member D. Peptides within the vasodilatory axis of the RAS are involved in vasodilation, blood pressure reduction, antihypertrophy, and antihyperplasia suggesting a plausible antihypertensive role of this axis [31,32].…”

L’alamandine, une nouvelle molécule d’intérêt thérapeutique contre l’hypertrophie cardiaque

“…Le RAS est un système conservé au cours de l'évolution chez les vertébrés. Il joue un rôle crucial dans certaines pathologies cardiovasculaires, telles que l'hypertension, l'insuffisance cardiaque et l'athérosclérose [2]. Les composants du RAS sont l'angiotensinogène, une α-2-globuline produite principalement par le foie, ainsi par l'équipe de Lautner [7].…”

“…Les composants du RAS sont l'angiotensinogène, une α-2-globuline produite principalement par le foie, ainsi par l'équipe de Lautner [7]. Elle peut être générée par la décarboxylation 1 de l'ANG-(1-7) [2]. Il a été montré qu'elle exerce des actions vasodilatatrices et anti-hypertensives via le récepteur MrgD (Mas-related G-protein-coupled receptor member D), un récepteur couplé aux protéines G apparenté à Mas, un récepteur activé par l'ANG-(1-7) [1,2] (Figure 1).…”

“…Elle peut être générée par la décarboxylation 1 de l'ANG-(1-7) [2]. Il a été montré qu'elle exerce des actions vasodilatatrices et anti-hypertensives via le récepteur MrgD (Mas-related G-protein-coupled receptor member D), un récepteur couplé aux protéines G apparenté à Mas, un récepteur activé par l'ANG-(1-7) [1,2] (Figure 1). Toutefois, la sélectivité de ces deux peptides vis-à-vis des récepteurs MrgD et Mas n'est pas clairement établie.…”