Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival
            <i>in vivo</i>

Lobov, Ivan B.; Brooks, Peter C.; Lang, Richard A.

doi:10.1073/pnas.172161899

Cited by 602 publications

(510 citation statements)

References 26 publications

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“…29 In agreement is a recent in vivo study using the pupillary membrane, a transient ocular microvessel network, which shows that following VEGF inhibition, Ang2 promotes endothelial cell death and blood vessel regression. 53 This concept can be extended to the retina, as Ang2-deficient mice have abnormal vascular development, and following ROP exhibit no retinal neovascularization. 54 Furthermore, inhibition of the Tie2 receptor with adenovirus-mediated gene delivery also attenuates angiogenesis in mouse models of ROP and choroidal neovascularization.…”

Section: Discussionmentioning

confidence: 99%

Retinal Angiogenesis Is Mediated by an Interaction between the Angiotensin Type 2 Receptor, VEGF, and Angiopoietin

Sarlos

Rizkalla

Moravski

et al. 2003

The American Journal of Pathology

131

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There is evidence that angiotensin II, vascular endothelial growth factor (VEGF), angiopoietins, and their cognate receptors participate in retinal angiogenesis. We investigated whether angiotensin type 2-receptor blockade (AT2-RB) reduces retinal angiogenesis and alters the expression of VEGF/VEGF-R2 and angiopoietin-Tie2. Retinopathy of prematurity (ROP) was induced in Sprague Dawley (SD) rats by exposure to 80% oxygen from postnatal (P) days 0 to 11, followed by 7 days in room air. ROP shams were in room air from P0 -18. A group of ROP rats received the AT2-RB, PD123319, by mini-osmotic pump (5 mg/kg/day) from P11-18 (angiogenesis period). Evaluation of the retinal status of the AT2 receptor indicated that this receptor, as assessed by real-time PCR, immunohistochemistry, and in vitro autoradiography, was present in the retina, was more abundant than the AT1 receptor in the neonatal retina, and was increased in the ROP model. AT2-RB reduced retinal angiogenesis. VEGF and VEGF-R2 mRNA were increased in ROP and localized to blood vessels, ganglion cells, and the inner nuclear layer, and were decreased by PD123319. Angiopoietin2 and Tie2, but not angiopoietin1 mRNA were increased with ROP, and angiopoietin2 was reduced with PD123319. This study has identified a potential retinoprotective role for AT2-RB possibly mediated via interactions with VEGF-and angiopoietin-dependent pathways.

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Section: Discussionmentioning

confidence: 99%

Retinal Angiogenesis Is Mediated by an Interaction between the Angiotensin Type 2 Receptor, VEGF, and Angiopoietin

Sarlos

Rizkalla

Moravski

et al. 2003

The American Journal of Pathology

131

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“…In these regions, Ang-2 can block the action of Ang-1 through competitive inhibition, thereby destabilizing the vessel structure (84). However, delineating an unequivocal definition of the precise function of Ang-2 is proving somewhat challenging, since it very much depends on the context; for instance, in the presence of VEGF, Ang-2 can prime vessels to mount a robust pro-angiogenic response (89).…”

Section: Angiogenesis a Rate-limiting Step For At Expansion And Remomentioning

confidence: 99%

Adipose tissue remodeling and obesity

Sun¹,

Kusminski²,

Scherer³

2011

J. Clin. Invest.

1,545

1,381

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To fulfill its role as the major energy-storing tissue, adipose has several unique properties that cannot be seen in any other organ, including an almost unlimited capacity to expand in a non-transformed state. As such, the tissue requires potent mechanisms to remodel, acutely and chronically. Adipocytes can rapidly reach the diffusional limit of oxygen during growth; hypoxia is therefore an early determinant that limits healthy expansion. Proper expansion requires a highly coordinated response among many different cell types, including endothelial precursor cells, immune cells, and preadipocytes. There are therefore remarkable similarities between adipose expansion and growth of solid tumors, a phenomenon that presents both an opportunity and a challenge, since pharmacological interventions supporting healthy adipose tissue adaptation can also facilitate tumor growth. IntroductionAdipose tissue (AT) can respond rapidly and dynamically to alterations in nutrient deprivation and excess through adipocyte hypertrophy and hyperplasia, thereby fulfilling its major role in wholebody energy homeostasis. AT remodeling is an ongoing process that is pathologically accelerated in the obese state, and thus, features such as reduced angiogenic remodeling, ECM overproduction, a heightened state of immune cell infiltration and subsequent proinflammatory responses prevail in many obese fat-pads (1). However, not all AT expansion is necessarily associated with pathological changes. The concept of the "metabolically healthy obese" state (2) suggests that some individuals can preserve systemic insulin sensitivity on the basis of "healthy" AT expansion, bypassing all of the aforementioned pathological consequences associated with obesity (3), thereby also avoiding the obesity-associated lipotoxic side effects. Many physiologically relevant processes important for human AT remodeling can be studied in rodent models, with the added advantage that processes related to AT expansion and reduction can occur at an extremely rapid rate. A 24-hour fast in a mouse is associated with a dramatic loss of AT mass and an acute remodeling process that involves rapid infiltration of macrophages; moreover, merely 24 to 48 hours of exposure to a high-fat diet (HFD) can cause a prompt increase in adipocyte size (4). AT is therefore an ideal model system to study rapid alterations in tissue expansion and reduction, as it adapts to a differential nutrient supply. Here, we will focus on key aspects of the intricate dynamics of AT remodeling and subsequent inflammatory consequences that arise from obesity.

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“…5. The up-regulation of Angpt2 (an antagonist of the pro-angiogenic angiopoetin-1) in hypertensive IGF-1 deficient mice is significant, as angiopoetin 2 expression has been causally linked to capillary rarefaction (Lobov et al 2002;Cao et al 2007). Figure 6 shows the effects of IGF-1 deficiency and hypertension on the hippocampal expression of the angiogenesis inhibitors Serpinf1 (PEDF), f i b u l i n -5 ( F b l n 5 ) ( S u l l i v a n e t a l .…”

Section: Igf-1 Deficiency Exacerbates Hypertension-induced Cerebromicmentioning

confidence: 99%

Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging

Tarantini

Tucsek

Valcarcel‐Ares

et al. 2016

AGE

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Strong epidemiological and experimental evidence indicate that both age and hypertension lead to significant functional and structural impairment of the cerebral microcirculation, predisposing to the development of vascular cognitive impairment (VCI) and Alzheimer's disease. Preclinical studies establish a causal link between cognitive decline and microvascular rarefaction in the hippocampus, an area of brain important for learning and memory. Age-related decline in circulating IGF-1 levels results in functional impairment of the cerebral microvessels; however, the mechanistic role of IGF-1 deficiency in impaired hippocampal microvascularization remains elusive. The present study was designed to characterize the additive/synergistic effects of IGF-1 deficiency and hypertension on microvascular density and expression of genes involved in angiogenesis and microvascular AGE (2016) 38:273-289

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Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo

Cited by 602 publications

References 26 publications

Retinal Angiogenesis Is Mediated by an Interaction between the Angiotensin Type 2 Receptor, VEGF, and Angiopoietin

Retinal Angiogenesis Is Mediated by an Interaction between the Angiotensin Type 2 Receptor, VEGF, and Angiopoietin

Adipose tissue remodeling and obesity

Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging

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