Angiotensin II Induces Angiogenesis in the Hypoxic Adult Mouse Heart In Vitro Through an AT
            <sub>2</sub>
            –B2 Receptor Pathway

Munk, Veronica C.; Miguel, Lourdes Sánchez de; Petrimpol, Marco; Butz, Nicole; Banfi, Andrea; Eriksson, Urs; Hein, Lutz; Humar, Rok; Battegay, Edouard

doi:10.1161/hypertensionaha.106.080242

Cited by 47 publications

(32 citation statements)

References 49 publications

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“…This study confirms previous observations [15][16][17] that Ang II in small amounts induces capillary tube formation from vascular endothelial cells. In keeping with previous observations, we show that the proangiogenic effects of Ang II are mediated by AT1R activation.…”

Section: Discussionsupporting

confidence: 93%

Angiotensin II Induces Capillary Formation From Endothelial Cells Via the LOX-1–Dependent Redox-Sensitive Pathway

Dandapat

Mehta

2007

Hypertension

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Abstract-Angiotensin(1) Ang II type 1 receptor (AT1R) stimulation promotes endothelial cells proliferation; (2) Ang II induces capillary formation from endothelial cells by inducing the expression of vascular endothelial growth factor (VEGF) via nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase/reactive oxygen species (ROS) pathway; (3) ischemia-induced angiogenesis is mediated through AT1R-mediated upregulation of VEGF and its receptor; (4) AT1R antagonists and angiotensinconverting enzyme inhibitors inhibit tumor-associated angiogenesis in murine models; (5) VEGF-mediated angiogenesis is impaired by AT1R blockade in cardiomyopathic hamster hearts; and (6) coronary capillary angiogenesis is mediated via AT1R-mediated upregulation of VEGF at the insulin-resistant stage in the noninsulin-dependent diabetes mellitus rat model.LOX-1, a lectin-like scavenger receptor for oxidized low-density lipoprotein (LDL), is expressed primarily on endothelial cells. 3 This receptor is upregulated by Ang II. 4 In turn, activation of LOX-1 upregulates AT1R expression. 5 Activation of both AT1R and LOX-1 induces intense oxidative stress. 3 We postulated that interruption of this positive feedback loop between LOX-1 and AT1R activation might attenuate Ang II-induced angiogenesis. This concept was examined in 2 different models of capillary growth, first, an in vitro model of capillary formation in human coronary artery endothelial cells (HCAECs) and, second, an ex vivo model of capillary sprouting from mouse aortic rings.

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Section: Discussionsupporting

confidence: 93%

Angiotensin II Induces Capillary Formation From Endothelial Cells Via the LOX-1–Dependent Redox-Sensitive Pathway

Dandapat

Mehta

2007

Hypertension

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“…It has been shown that angiotensin II, through its effect on angiotensin type 2 receptor, and bradykinin level, via bradykinin type 2 receptor, may affect the microvascular structure and function. 1,30 In our study, there was a significant increase in plasma renin activity in whites only, whereas the increase in capillary density occurred in all 3 of the ethnic groups. It is not known how far the responses of the renin-angiotensin system contributed to the changes in capillary density.…”

Section: He Et Al Effect Of Salt Reduction On Capillary Rarefactioncontrasting

confidence: 39%

Effect of Modest Salt Reduction on Skin Capillary Rarefaction in White, Black, and Asian Individuals With Mild Hypertension

Marciniak

Markandu

et al. 2010

Hypertension

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Abstract-Microvascular rarefaction occurs in hypertension. We carried out a 12-week randomized double-blind crossover trial to determine the effect of a modest reduction in salt intake on capillary rarefaction in 71 whites, 69 blacks, and 29 Asians with untreated mildly raised blood pressure. Both basal and maximal (during venous congestion) skin capillary density were measured by capillaroscopy at the dorsum and the side of the fingers. In addition, we used orthogonal polarization spectral imaging to measure skin capillary density at the dorsum of the fingers and the hand web. With a reduction in salt intake from 9.7 to 6.5 g/day, there was an increase in capillary density (capillaries per millimeter squared) from 101Ϯ21 to 106Ϯ23 (basal) and 108Ϯ22 to 115Ϯ22 (maximal) at the dorsum, and 101Ϯ25 to 107Ϯ26 (basal) and 110Ϯ26 to 116Ϯ26 (maximal) at the side of the fingers (PϽ0.001 for all). Orthogonal polarization spectral imaging also showed a significant increase in capillary density both at the dorsum of the fingers and the web. Subgroup analysis showed that most of the changes were significant in all of the ethnic groups. Furthermore, there was a significant relationship between the change in 24-hour urinary sodium and the change in capillary density at the side of the fingers. These results demonstrate that a modest reduction in salt intake, as currently recommended, improves both functional and structural capillary rarefactions that occur in hypertension, and a larger reduction in salt intake would have a greater effect. The increase in capillary density may possibly carry additional beneficial effects on target organs. (Hypertension. 2010;56:253-259.)Key Words: sodium Ⅲ dietary Ⅲ microcirculation Ⅲ capillary rarefaction Ⅲ hypertension Ⅲ randomized trial M icrovascular rarefaction, that is, a reduction in the number of arterioles and capillaries, is found in many animal models of hypertension and in human hypertension. 1,2 We have shown previously that much of the reduction in capillary density in essential hypertension was because of the structural (anatomic) absence of capillaries, 2 although functional capillary rarefaction (because of nonperfusion) also existed. 1 Our previous studies also suggested that capillary rarefaction was likely to be a primary vascular abnormality. 3,4 Microvascular rarefaction increases peripheral vascular resistance, thereby increasing blood pressure (BP) and aggravating BP-related target organ damage. 1 At the same time, a reduction in the microvascular network may decrease tissue perfusion 5 and cause gradual impairments of tissues and organs. Two studies have implied that long-term effective antihypertensive treatments may reverse microvascular rarefaction in nondiabetic individuals with raised BP. 6 -8 Studies in rats demonstrated that a high-salt intake caused a significant loss of microvessels, 9,10 which occurred within a few days. 10 However, no controlled trial in humans has studied whether a modest reduction in salt intake has an effect on microcirculation.Direct in...

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“…In some studies a partial blockade was obtained with the AT 2 antagonist PD 123319 when a partial inhibition was also seen with A-779 and the B 2 receptor antagonist Hoe 140. Likewise, some BK effects are attenuated by PD 123319 (Bergaya et al 2004) and some AT 2 -mediated effects are attenuated by B 2 receptor blockade (Munk et al 2007). These observations illustrate the intricate relationship between Ang and kinin receptors, suggesting intracellular interactions via common signaling pathways or heterodimerization.…”

Section: Metabolic Actions Of the Ace2/ang-(1-7)/mas Axismentioning

confidence: 99%

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

Santos

Ferreira

Verano‐Braga

et al. 2012

Journal of Endocrinology

430

369

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Angiotensin (Ang)-(1-7) is now recognized as a biologically active component of the reninangiotensin 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. This enzyme can form Ang-(1-7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1-9) with subsequent Ang-(1-7) formation by ACE. In addition, it is now well established that the G protein-coupled receptor Mas is a functional binding site for Ang-(1-7). Thus, the axis formed by ACE2/Ang-(1-7)/Mas appears to represent an endogenous counterregulatory pathway within the RAS, the actions of which are in opposition to the vasoconstrictor/ proliferative arm of the RAS consisting of ACE, Ang II, and AT 1 receptor. In this brief review, we will discuss recent findings related to the biological role of the ACE2/Ang-(1-7)/Mas arm in the cardiovascular and renal systems, as well as in metabolism. In addition, we will highlight the potential interactions of Ang-(1-7) and Mas with AT 1 and AT 2 receptors.

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Angiotensin II Induces Angiogenesis in the Hypoxic Adult Mouse Heart In Vitro Through an AT ₂ –B2 Receptor Pathway

Cited by 47 publications

References 49 publications

Angiotensin II Induces Capillary Formation From Endothelial Cells Via the LOX-1–Dependent Redox-Sensitive Pathway

Angiotensin II Induces Capillary Formation From Endothelial Cells Via the LOX-1–Dependent Redox-Sensitive Pathway

Effect of Modest Salt Reduction on Skin Capillary Rarefaction in White, Black, and Asian Individuals With Mild Hypertension

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

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Angiotensin II Induces Angiogenesis in the Hypoxic Adult Mouse Heart In Vitro Through an AT 2 –B2 Receptor Pathway

Cited by 47 publications

References 49 publications

Angiotensin II Induces Capillary Formation From Endothelial Cells Via the LOX-1–Dependent Redox-Sensitive Pathway

Angiotensin II Induces Capillary Formation From Endothelial Cells Via the LOX-1–Dependent Redox-Sensitive Pathway

Effect of Modest Salt Reduction on Skin Capillary Rarefaction in White, Black, and Asian Individuals With Mild Hypertension

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

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Angiotensin II Induces Angiogenesis in the Hypoxic Adult Mouse Heart In Vitro Through an AT ₂ –B2 Receptor Pathway