Treatment with Evasin-3 reduces atherosclerotic vulnerability for ischemic stroke, but not brain injury in mice.

Neutrophilic inflammation might have a pathophysiological role in both carotid plaque rupture and ischemic stroke injury. Here, we investigated the potential benefits of the CXC chemokine-binding protein Evasin-3, which potently inhibits chemokine bioactivity and related neutrophilic inflammation in two mouse models of carotid atherosclerosis and ischemic stroke, respectively. In the first model, the chronic treatment with Evasin-3 as compared with Vehicle (phosphate-buffered saline (PBS)) was investigated in apolipoprotein E-deficient mice implanted of a 'cast' carotid device.

Angiotensin-(1-7): beyond the cardio-renal actions.

It is well known that the RAS (renin-angiotensin system) plays a key role in the modulation of many functions in the body. AngII (angiotensin II) acting on AT1R (type 1 AngII receptor) has a central role in mediating most of the actions of the RAS. However, over the past 10 years, several studies have presented evidence for the existence of a new arm of the RAS, namely the ACE (angiotensin-converting enzyme) 2/Ang-(1-7) [angiotensin-(1-7)]/Mas axis.

Opportunities for targeting the angiotensin-converting enzyme 2/angiotensin-(1-7)/mas receptor pathway in hypertension.

It is well known that the renin-angiotensin system (RAS) plays a pivotal role in the pathophysiology of cardiovascular diseases. This is well illustrated by the great success of ACE inhibitors and angiotensin (Ang) II AT(1) blockers in the treatment of hypertension and its complications. In the past decade, the classical concept of RAS orchestrated by a series of enzymatic reactions culminating in the linear generation and action of Ang II has expanded and become more complex.

The angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptor axis: a potential target for treating thrombotic diseases.

Despite many therapeutic advances leading to increasingly effective drug treatments, thrombotic events (such as ischaemic stroke, pulmonary embolism, deep venous thrombosis and acute myocardial infarction) still represent a major worldwide cause of morbidity and mortality. Remarkable effort has been made to identify new drug targets. There is growing evidence indicating that the recently described counter-regulator axis of the renin-angiotensin system (RAS), composed of Angiotensin-Converting Enzyme 2 (ACE2), Angiotensin-(1-7) and the Mas receptor, has protective effects against thrombosis.

Angiotensin-converting enzyme 2, angiotensin-(1-7) and Mas: new players of the renin-angiotensin system.

Angiotensin (Ang)-(1-7) is now recognized as a biologically active component of the renin-angiotensin system (RAS). Ang-(1-7) appears to play a central role in the RAS because it exerts a vast array of actions, many of them opposite to those attributed to the main effector peptide of the RAS, Ang II. The discovery of the Ang-converting enzyme (ACE) homolog ACE2 brought to light an important metabolic pathway responsible for Ang-(1-7) synthesis.

Altered regional blood flow distribution in Mas-deficient mice.

Background: We have recently shown that the acute infusion of angiotensin-(1-7) [Ang-(1-7)] or chronic increase in plasma Ang-(1-7) produces important changes in regional blood flow in rats.

Methods: To further assess whether these changes are related to Mas, in this study hemodynamic measurements were performed in Ang-(1-7) receptor Mas knockout C57BL/6 (Mas-KO) mice and age-matched wild type (WT) control mice, using fluorescent microspheres.

Results: Mean arterial pressure in urethane-anesthetized Mas-KO mice (12-16 weeks old) did not differ from that in WT mice (79 ± 2 and 80 ± 2 mmHg respectively).

AVE 0991, a non-peptide Mas-receptor agonist, facilitates penile erection.

The renin-angiotensin system plays a crucial role in erectile function. It has been shown that elevated levels of angiotensin II contribute to the development of erectile dysfunction both in humans and in aminals. On the contrary, the heptapeptide angiotensin-(1-7) appears to mediate penile erection by activation of the Mas receptor.

Exercise induces renin-angiotensin system unbalance and high collagen expression in the heart of Mas-deficient mice.

The renin-angiotensin system (RAS) is involved in the cardiac and vascular remodeling associated with cardiovascular diseases. Angiotensin (Ang) II/AT(1) axis is known to promote cardiac hypertrophy and collagen deposition. In contrast, Ang-(1-7)/Mas axis opposes Ang II effects in the heart producing anti-trophic and anti-fibrotic effects.

Decreased hepatic gluconeogenesis in transgenic rats with increased circulating angiotensin-(1-7).

The renin-angiotensin (Ang) system (RAS) plays an important role in the control of glucose metabolism and glycemia. Several studies demonstrated that the effects of angiotensin-(1-7) are mainly opposite to the actions of biological angiotensin II. Recent studies have demonstrated that rats with increased circulating angiotensin-(1-7), acting through the G protein coupled receptor Mas, have enhanced glucose tolerance and insulin sensitivity, presenting improved metabolic parameters.

Contribution of infralimbic cortex in the cardiovascular response to acute stress.

The infralimbic region of the medial prefrontal cortex (IL) modulates autonomic and neuroendocrine function via projections to subcortical structures involved in the response to stress. We evaluated the contribution of the IL to the cardiovascular response evoked by acute stress. Under anesthesia (80 mg/kg ketamine-11.

Increased circulating angiotensin-(1-7) protects white adipose tissue against development of a proinflammatory state stimulated by a high-fat diet.

Introduction: The aim of the present study was to evaluate the effect of a transgenic-induced chronic increase of Ang-(1-7) on the expression of inflammatory markers in adipose tissue and the metabolic profile in rats treated with high-fat diet.

Research Design And Methods: Transgenic rats expressing an Ang-(1-7)-producing fusion protein (TGR L-3292) and Sprague Dawley (SD) control rats 4 weeks old were treated for 8 weeks with a high-fat diet. Food intake and body weight were measured once a week.

Tissue specific localization of angiotensin-(1-7) and its receptor Mas in the uterus of ovariectomized rats.

The vasoactive peptide angiotensin (Ang)-(1-7) has vasodilator, antifibrotic and antihypertrophic properties, but little is known about its regulation in the uterus. The aim of this study was to evaluate Ang-(1-7) and its receptor Mas expression throughout rat uterine tissues, in ovariectomized animals treated with estrogen alone or combined with progestin. Adult Wistar rats (n = 19) were ovariectomized and randomly assigned into three different groups 1 week later.

Chronic infusion of angiotensin-(1-7) into the lateral ventricle of the brain attenuates hypertension in DOCA-salt rats.

Angiotensin-(ANG)-(1-7) is known by its central and peripheral actions, which mainly oppose the deleterious effects induced by accumulation of ANG II during pathophysiological conditions. In the present study we evaluated whether a chronic increase in ANG-(1-7) levels in the brain would modify the progression of hypertension. After DOCA-salt hypertension was induced for seven days, Sprague-Dawley rats were subjected to 14 days of intracerebroventricular (ICV) infusion of ANG-(1-7) (200 ng/h, DOCA-A7) or 0.

Oral administration of an angiotensin-converting enzyme 2 activator ameliorates diabetes-induced cardiac dysfunction.

We evaluated the hypothesis that activation of endogenous angiotensin-converting enzyme (ACE) 2 would improve cardiac dysfunction induced by diabetes. Ten days after diabetes induction (streptozotocin, 50 mg/kg, i.v.

Update on the role of cannabinoid receptors after ischemic stroke.

Cannabinoids are considered as key mediators in the pathophysiology of inflammatory diseases, including atherosclerosis. In particular, they have been shown to reduce the ischemic injury after acute cardiovascular events, such as acute myocardial infarction and ischemic stroke. These protective and anti-inflammatory properties on peripheral tissues and circulating inflammatory have been demonstrated to involve their binding with both selective cannabinoid type 1 (CB₁ and type 2 (CB₂) transmembrane receptors.

Angiotensin-(1-7)-mediated signaling in cardiomyocytes.

The Renin-Angiotensin System (RAS) acts at multiple targets and has its synthesis machinery present in different tissues, including the heart. Actually, it is well known that besides Ang II, the RAS has other active peptides. Of particular interest is the heptapeptide Ang-(1-7) that has been shown to exert cardioprotective effects.

Therapeutic targeting of the angiotensin-converting enzyme 2/Angiotensin-(1-7)/Mas cascade in the renin-angiotensin system: a patent review.

Introduction: The renin-angiotensin system (RAS) is a main therapeutic target for cardiovascular diseases. Within the last two decades, novel components of the RAS have been discovered, opening new opportunities to interfere with its activity. Angiotensin(Ang)-(1-7) is synthesized by angiotensin-converting enzyme 2 (ACE2), and interacts with the G-protein-coupled receptor Mas.

The cardiac expression of Mas receptor is responsive to different physiological and pathological stimuli.

The Mas protooncogene encodes a G protein-coupled receptor that has been described as a functional receptor for the cardioprotective fragment of the renin-angiotensin system (RAS), Angiotensin (Ang)-(1-7). The aim of this current study was to evaluate the responsiveness of Mas expression in hearts during different physiological and pathological conditions in rats. Physical training was considered a physiological condition, while isoproterenol-induced hypertrophy, myocardial infarction and DOCA-salt model of hypertension were used as pathological models of heart injury.

Time-resolved quantitative phosphoproteomics: new insights into Angiotensin-(1-7) signaling networks in human endothelial cells.

Angiotensin-(1-7) [Ang-(1-7)] is an endogenous ligand of the Mas receptor and induces vasodilation, positive regulation of insulin, and antiproliferative and antitumorigenic activities. However, little is known about the molecular mechanisms behind these biological properties. Aiming to identify proteins involved in the Ang-(1-7) signaling, we performed a mass spectrometry-based time-resolved quantitative phosphoproteome study of human aortic endothelial cells (HAEC) treated with Ang-(1-7).

Beneficial effects of long-term administration of an oral formulation of Angiotensin-(1-7) in infarcted rats.

In this study was evaluated the chronic cardiac effects of a formulation developed by including angiotensin(Ang)-(1-7) in hydroxypropyl β-cyclodextrin (HPβCD), in infarcted rats. Myocardial infarction (MI) was induced by left coronary artery occlusion. HPβCD/Ang-(1-7) was administered for 60 days (76 μg/Kg/once a day/gavage) starting immediately before infarction.

Angiotensin-(1-7) induces peripheral antinociception through mas receptor activation in an opioid-independent pathway.

The G protein-coupled receptor Mas was recently described as an angiotensin-(1-7) [Ang-(1-7)] receptor. In the present study, we demonstrate an antinociceptive effect of Ang-(1-7) for the first time. Additionally, we evaluated the anatomical localization of Mas in the dorsal root ganglia using immunofluorescence.

Cardiovascular responses evoked by activation or blockade of GABA(A) receptors in the hypothalamic PVN are attenuated in transgenic rats with low brain angiotensinogen.

Previous evidence indicates that a balance between inhibitory gabaergic and excitatory angiotensinergic factors in the PVN is important for cardiovascular control. We investigated the cardiovascular response evoked from activation or blockade of GABA(A) receptors in the paraventricular nucleus (PVN), in transgenic rats with low brain angiotensinogen [TGR(ASrAOGEN)]. Brain Ang II and Ang-(1-7) levels were also determined.

Renoprotective Effects of AVE0991, a Nonpeptide Mas Receptor Agonist, in Experimental Acute Renal Injury.

Renal ischemia and reperfusion (I/R) is the major cause of acute kidney injury in hospitalized patients. Mechanisms underlying reperfusion-associated injury include recruitment and activation of leukocytes and release of inflammatory mediators. In this study, we investigated the renal effects of acute administration of AVE0991, an agonist of Mas, the angiotensin-(1-7) receptor, the angiotensin-(1-7) receptor, in a murine model of renal I/R.