Impaired angiogenesis in SHR is associated with decreased KDR and MT1-MMP expression

He, Wei‐Ming; Olszewski, Bronia; Rosebury, Wendy S.; Wang, Dongkai; Robertson, Andrew W.; Keiser, Joan A.

doi:10.1016/j.bbrc.2004.01.059

Cited by 34 publications

(28 citation statements)

References 32 publications

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“…These data were in keeping with previous reports showing an increase of aortic elastin content in hypertensive animals (Keeley and Alatawi, 1991); hypertension was also associated with elastin haploinsufficiency in human and mice (Faury et al, 2003). By contrast, angiogenesis was restored by increasing the levels of VEGFR-2 and MT1-MMP using a sponge implantation model associated to a VEGF gene transfer technology in SHR (Wang et al, 2004). However, the aortic elastin content was not appreciated in this study.…”

Section: Discussionsupporting

confidence: 75%

“…In addition, as MT1-MMP is overexpressed by proinflammatory molecules, it might also contribute to the enhanced local matrix degradation in human atherosclerotic plaques as previously reported (Rajavashisth et al, 1999;Hong et al, 2000). On the other hand, decreased arteriolar and capillary density in a spontaneous hypertensive rat (SHR) model correlated with decreased MT1-MMP and VEGF receptor expression (VEGFR-2) (Wang et al, 2004). These data were in keeping with previous reports showing an increase of aortic elastin content in hypertensive animals (Keeley and Alatawi, 1991); hypertension was also associated with elastin haploinsufficiency in human and mice (Faury et al, 2003).…”

Section: Discussionmentioning

confidence: 71%

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Elastin-derived peptides enhance angiogenesis by promoting endothelial cell migration and tubulogenesis through upregulation of MT1-MMP

Robinet

Fahem

Cauchard

et al. 2005

Journal of Cell Science

218

172

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Elastin-derived peptides display a wide range of biological activities in a number of normal and transformed cells but their involvement in angiogenesis has not been reported. In the present study, we show that κ-elastin and VGVAPG hexapeptide elastin motif accelerated angiogenesis in the chick chorio-allantoic membrane in an in vivo model. They also stimulated pseudotube formation from human vascular and microvascular endothelial cells in the matrigel and collagen models as well as cell migration in an in vitro wound healing assay. Confocal and scanning electron microscopy analyses revealed the main reorganization of actin filaments mediated by elastin-derived peptides and changes in cell shape that correlated with a decrease of the cell form factor determined by computerized image analysis. Such elastin-derived peptide effects were attributed to upregulation of proMT1-MMP and proMMP-2 expression and activation at both the mRNA and protein levels. Batimastat, an inhibitor of furin convertase and TIMP-2, but not TIMP-1, totally abolished the influence of elastin-derived peptides (EDPs) on cell migration and tubulogenesis, thus favoring the involvement of MT1-MMP in such processes. To assess its contribution to EDP-mediated angiogenesis further, we used a small interfering RNA (siRNA) approach for specifically silencing MT1-MMP in human microvascular endothelial cells. Four sets of 21 bp siRNA duplexes targeting MT1-MMP mRNA were synthesized by in vitro transcription. Two of them proved to inhibit MT1-MMP expression efficiently but did not affect MT2-, MT3- and MT5-MMP expression. Seventy-two hours after transfection with 25 nM siRNAs EDP-induced MT1-MMP expression at the mRNA and protein levels was decreased fourfold. In parallel, proMMP-2 activation was inhibited. A scrambled siRNA, used as a negative control, had no effect. Finally, the effect of elastin peptides on pseudotube formation in MT1-MMP-siRNA transfected cells was totally abolished. These data emphasise the crucial role of MT1-MMP in the elastin-induced angiogenic phenotype of endothelial cells.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 71%

Elastin-derived peptides enhance angiogenesis by promoting endothelial cell migration and tubulogenesis through upregulation of MT1-MMP

Robinet

Fahem

Cauchard

et al. 2005

Journal of Cell Science

218

172

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“…Although this report is the first causal link between endogenous angiogenesis and neurogenesis after stroke, other studies have noted a link between vascular markers or growth factors and neurogenesis after stroke (Wang et al, 2004b;Greenberg and Jin, 2005;Jin et al, 2006;Tsai et al, 2006;Robin et al, 2006). Animal strains with reduced angiogenesis (Wang et al, 2004a) do not show long-distance neuroblast migration (Komitova et al, 2005). Despite the vascular/neurogenesis associations in these studies and the present data, it has also been reported that stroke induces neuroblasts to associate with astrocytes as they migrate into damaged tissue in some stroke models.…”

Section: Discussioncontrasting

confidence: 55%

A Neurovascular Niche for Neurogenesis after Stroke

Ohab¹,

Fleming²,

Blesch³

et al. 2006

J. Neurosci.

792

783

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Stroke causes cell death but also birth and migration of new neurons within sites of ischemic damage. The cellular environment that induces neuronal regeneration and migration after stroke has not been defined. We have used a model of long-distance migration of newly born neurons from the subventricular zone to cortex after stroke to define the cellular cues that induce neuronal regeneration after CNS injury. Mitotic, genetic, and viral labeling and chemokine/growth factor gain-and loss-of-function studies show that stroke induces neurogenesis from a GFAP-expressing progenitor cell in the subventricular zone and migration of newly born neurons into a unique neurovascular niche in peri-infarct cortex. Within this neurovascular niche, newly born, immature neurons closely associate with the remodeling vasculature. Neurogenesis and angiogenesis are causally linked through vascular production of stromal-derived factor 1 (SDF1) and angiopoietin 1 (Ang1). Furthermore, SDF1 and Ang1 promote post-stroke neuroblast migration and behavioral recovery. These experiments define a novel brain environment for neuronal regeneration after stroke and identify molecular mechanisms that are shared between angiogenesis and neurogenesis during functional recovery from brain injury.

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“…Indeed, decreased MMP activity/ expression has been associated with NO inhibition and increased collagen deposition (25,26,36,59). The literature describing MMP expression in pregnancy-induced hypertension is conflicting; some studies (32,67) suggest that MMPs are increased in preeclampsia while others found that ECM degradation is compromised in preeclampsia due to decreased MMP expression. These disparate results could be due to sampling location, since studies that evaluate serum or plasma levels of MMPs in preeclampsia generally report elevated levels of MMPs while those that evaluate MMP and TIMP expression within the umbilical cord artery or the placenta report decreased expression of MMPs and TIMPs (14,15,37,45,52).…”

Section: Discussionmentioning

confidence: 99%

Reduced NO signaling during pregnancy attenuates outward uterine artery remodeling by altering MMP expression and collagen and elastin deposition

Hale

Weger

Mandalà

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Hale SA, Weger L, Mandala M, Osol G. Reduced NO signaling during pregnancy attenuates outward uterine artery remodeling by altering MMP expression and collagen and elastin deposition. Am J Physiol Heart Circ Physiol 301: H1266 -H1275, 2011. First published August 19, 2011 doi:10.1152/ajpheart.00519.2011.-Recent findings indicate that endothelial nitric oxide (NO) plays a key role in uterine artery outward circumferential remodeling during pregnancy. Although the underlying mechanisms are not known, they likely involve matrix metalloproteinases (MMPs). The goal of this study was to examine the linkage among NO inhibition, expansive remodeling, and MMP expression within the uterine vascular wall. Adult female rats were treated with N G -nitro-L-arginine methyl ester [L-NAME (LPLN)] beginning on day 10 of pregnancy and until death at day 20 and compared with age-matched controls [late pregnant (LP)]. Mean arterial pressure of LPLN rats was significantly higher than controls. LPLN fetal and placental weights were significantly reduced compared with controls. Main uterine arteries (mUA) were collected to determine dimensional properties (lumen area and wall thickness), collagen and elastin content, and levels of endothelial nitric oxide synthase (eNOS) and MMP expression. Circumferential remodeling was attenuated, as evidenced by significantly smaller lumen diameters. eNOS RNA and protein were significantly (Ͼ90%) decreased in the LPLN mUA compared with LP. Collagen and elastin contents were significantly increased in LPLN rats by ϳ10 and 25%, respectively, compared with LP (P Ͻ 0.05). Both MMP-2 and tissue inhibitors of metalloproteinase-2 as assessed by immunofluorescence were lower in the endothelium (reduction of 60%) and adventitia (reduction of 50%) of LPLN compared with LP mUA. Membrane bound MMP-1 (MT1-MMP) as assessed by immunoblot was significantly decreased in LPLN. These data suggest a novel contribution of MMPs to gestational uterine vascular remodeling and substantiate the linkage between NO signaling and gestational remodeling of the uterine circulation via altered MMP, TIMP-2, and MT1-MMP expression and activity. matrix metalloproteinase; extracellular matrix; hypertension; pregnancy; nitric oxide DURING PREGNANCY, THE UTERINE vasculature undergoes significant expansive remodeling to accommodate the dramatic increase in uteroplacental blood flow that is requisite for normal pregnancy outcome. Studies from our and other laboratories (40,41,44,46,50,61) have established that nitric oxide (NO) is a key molecule involved in vascular remodeling during pregnancy and that expression of endothelial nitric oxide synthase (eNOS) is increased during pregnancy, leading to increased synthesis and release of NO from the endothelium.The importance of NO and NO signaling during pregnancy is underscored by the vascular and reproductive implications evident in mouse knockouts for endothelial NO synthase and in rats treated with the NO inhibitor N G -nitro-L-arginine methyl ester (L-NAME) during pregnancy (50, 64). Tre...

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Impaired angiogenesis in SHR is associated with decreased KDR and MT1-MMP expression

Cited by 34 publications

References 32 publications

Elastin-derived peptides enhance angiogenesis by promoting endothelial cell migration and tubulogenesis through upregulation of MT1-MMP

Elastin-derived peptides enhance angiogenesis by promoting endothelial cell migration and tubulogenesis through upregulation of MT1-MMP

A Neurovascular Niche for Neurogenesis after Stroke

Reduced NO signaling during pregnancy attenuates outward uterine artery remodeling by altering MMP expression and collagen and elastin deposition

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