Angiotensin-(1–7) Protects From Experimental Acute Lung Injury

Klein, Nadine; Gembardt, Florian; Supé, Stephanie; Kaestle, Stephanie M.; Nickles, Hannah T.; Erfinanda, Lasti; Lei, Xiaoguang; Yin, Jun; Wang, Liming; Mertens, Michael; Szászi, Katalin; Walther, Thomas; Kuebler, Wolfgang M.

doi:10.1097/ccm.0b013e31828a6688

Cited by 111 publications

(105 citation statements)

References 43 publications

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“…9 Therefore, we aimed to identify and quantify a second messenger stimulated by Ang-(1-7) allowing pharmacological confirmation of Mas as a functional heptapeptide receptor, to understand the postulated interaction between AT2 and Ang-(1-7), and to discover the hypothetical second receptor, by working with primary and receptor-transfected cells and in vivo approaches.…”

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confidence: 99%

G-Protein–Coupled Receptor MrgD Is a Receptor for Angiotensin-(1–7) Involving Adenylyl Cyclase, cAMP, and Phosphokinase A

et al. 2016

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Angiotensin (Ang)-(1–7) has cardiovascular protective effects and is the opponent of the often detrimental Ang II within the renin–angiotensin system. Although it is well accepted that the G-protein–coupled receptor Mas is a receptor for the heptapeptide, the lack in knowing initial signaling molecules stimulated by Ang-(1–7) prevented definitive characterization of ligand/receptor pharmacology as well as identification of further hypothesized receptors for the heptapeptide. The study aimed to identify a second messenger stimulated by Ang-(1–7) allowing confirmation as well as discovery of the heptapeptide’s receptors. Ang-(1–7) elevates cAMP concentration in primary cells, such as endothelial or mesangial cells. Using cAMP as readout in receptor-transfected human embryonic kidney (HEK293) cells, we provided pharmacological proof that Mas is a functional receptor for Ang-(1–7). Moreover, we identified the G-protein–coupled receptor MrgD as a second receptor for Ang-(1–7). Consequently, the heptapeptide failed to increase cAMP concentration in primary mesangial cells with genetic deficiency in both Mas and MrgD . Mice deficient in MrgD showed an impaired hemodynamic response after Ang-(1–7) administration. Furthermore, we excluded the Ang II type 2 receptor as a receptor for the heptapeptide but discovered that the Ang II type 2 blocker PD123319 can also block Mas and MrgD receptors. Our results lead to an expansion and partial revision of the renin–angiotensin system, by identifying a second receptor for Ang-(1–7), by excluding Ang II type 2 as a receptor for the heptapeptide, and by enforcing the revisit of such publications which concluded Ang II type 2 function by only using PD123319.

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G-Protein–Coupled Receptor MrgD Is a Receptor for Angiotensin-(1–7) Involving Adenylyl Cyclase, cAMP, and Phosphokinase A

et al. 2016

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“…Ang-(1-7)-treated animals also displayed less histological evidence of lung injury, less myeloperoxidase activity in lung samples, and lower pulmonary artery resistance as compared to nontreated animals with experimental lung injury (110). These data suggest that Ang-(1-7)-based therapies could be promising tools for the prevention and treatment of acute lung injury from a variety of stimuli.…”

Section: Ace2 and Angiotensin-(1-7)mentioning

confidence: 79%

“…edema (110). Ang-(1-7)-treated animals also displayed less histological evidence of lung injury, less myeloperoxidase activity in lung samples, and lower pulmonary artery resistance as compared to nontreated animals with experimental lung injury (110).…”

Section: Ace2 and Angiotensin-(1-7)mentioning

confidence: 94%

“…Indeed, a search for Ang-(1-7)-based therapeutics is underway. The basis for such a search is strengthened by our own work performed in three animal models of acute lung injury, namely acid inhalation, ventilated-induced lung injury, and oleic acid instillation (110). These experiments indicated that delivery of exogenous Ang-(1-7) protected rodents from pulmonary , which subsequently binds the Mas receptor.…”

Section: Ace2 and Angiotensin-(1-7)mentioning

confidence: 99%

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Endothelial Cell Regulation of Pulmonary Vascular Tone, Inflammation, and Coagulation

Goldenberg

Kuebler

2015

Comprehensive Physiology

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The pulmonary endothelium represents a heterogeneous cell monolayer covering the luminal surface of the entire lung vasculature. As such, this cell layer lies at a critical interface between the blood, airways, and lung parenchyma, and must act as a selective barrier between these diverse compartments. Lung endothelial cells are able to produce and secrete mediators, display surface receptor, and cellular adhesion molecules, and metabolize circulating hormones to influence vasomotor tone, both local and systemic inflammation, and coagulation functions. In this review, we will explore the role of the pulmonary endothelium in each of these systems, highlighting key regulatory functions of the pulmonary endothelial cell, as well as novel aspects of the pulmonary endothelium in contrast to the systemic cell type. The interactions between pulmonary endothelial cells and both leukocytes and platelets will be discussed in detail, and wherever possible, elements of endothelial control over physiological and pathophysiological processes will be examined. C 2015 American Physiological Society.

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“…However, so far, most of our knowledge about the RAS system during septic shock has come from a few experimental studies performed with healthy rodents [17,[21][22][23][24][25][26], sheep [27,28] or pigs [7]. The role of exogenous angiotensin II administration or its inhibition in sepsis is poorly understood [29].…”

Section: Angiotensin II Receptorsmentioning

confidence: 99%

Angiotensin II in Septic Shock

Corrêa¹,

Takala²,

Jakob³

2015

Annual Update in Intensive Care and Emergency Medicine

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Angiotensin-(1–7) Protects From Experimental Acute Lung Injury

Abstract: Angiotensin-(1-7) or its analogs attenuate the key features of acute lung injury and may present a promising therapeutic strategy for the treatment of this disease.

Cited by 111 publications

References 43 publications

G-Protein–Coupled Receptor MrgD Is a Receptor for Angiotensin-(1–7) Involving Adenylyl Cyclase, cAMP, and Phosphokinase A

G-Protein–Coupled Receptor MrgD Is a Receptor for Angiotensin-(1–7) Involving Adenylyl Cyclase, cAMP, and Phosphokinase A

Endothelial Cell Regulation of Pulmonary Vascular Tone, Inflammation, and Coagulation

Angiotensin II in Septic Shock

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