Published online before print November 22, 2004, doi: 10.1161/01.CIR.0000148780.36121.47
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2004;110:3587-3593.)
© 2004 American Heart Association, Inc.
Molecular Cardiology |
Involvement of Metalloproteinases 2/9 in Epidermal Growth Factor Receptor Transactivation in Pressure-Induced Myogenic Tone in Mouse Mesenteric Resistance Arteries
From the Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans (P.A.L., K.M.), and the Department of Physiology and Biophysics, University of Alabama at Birmingham (A.S., S.B.).
Correspondence to Khalid Matrougui, PhD, Department of Pharmacology, 1901 Perdido St, Suite 701, New Orleans, LA 70112. E-mail kmatro{at}lsuhsc.edu
Received May 11, 2004; revision received August 4, 2004; accepted September 8, 2004.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background— Epidermal growth factor receptor (EGFR) transactivation is a mediator of angiotensin II (Ang II) signaling in cultured vascular smooth muscle cells isolated from large arteries. The present study used mouse mesenteric resistance arteries (MRAs) to investigate the role of EGFR transactivation under pressure-induced myogenic tone (MT).
Methods and Results— Isolated MRAs were mounted in an arteriograph and stimulated by 25 to 125 mm Hg or with Ang II and KCl. Stepwise increases in pressure resulted in MT development associated with increased EGFR phosphorylation and release of heparin-binding EGF (HB-EGF), a membrane-bound growth factor that is shed on cleavage by metalloproteinases. EGF (50 ng/mL) potentiated MT (59±1% to 51±0.6% of passive diameter at 75 mm Hg). Pretreatment with the EGFR inhibitors AG1478 (5 µmol/L) or PD153035 (1 µmol/L) significantly decreased MT. However, EGFR inhibitors had no effect on Ang II– and KCl-induced contraction. MT was potentiated by HB-EGF, 50 ng/mL, which is bound to the cell membrane and released on cleavage by metalloproteinases. Neutralizing HB-EGF antibodies or heparin treatment to sequester HB-EGF resulted in significant inhibition of pressure-induced MT. MT increased matrix metalloproteinase (MMP) 2 and MMP-9 gelatinase activity assessed by zymography, and specific MMP 2/9 inhibitors significantly decreased MT.
Conclusions— These novel findings suggest that the mechanism of pressure-induced MT involves metalloproteinases 2/9 activation with subsequent HB-EGF release and EGFR transactivation.
Key Words: microcirculation • metalloproteinases • growth substances • angiotensin • pressure
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Resistance artery diameter is markedly sensitive to changes in intraluminal pressure compared with the large artery. In general, these arteries contract in response to increased pressure and dilate in response to pressure reduction. This behavior, called myogenic tone (MT), is an inherent property of vascular smooth muscle cells (VSMCs) of resistance arteries and is modulated by neural, metabolic, and hormonal influences.1 Under physiological conditions, MT is crucial for the control of peripheral resistance basal tone, maintenance of constant blood flow, and capillary hydrostatic pressure during variations in systemic arterial pressure.1 However, in cardiovascular disease such as hypertension, changes in total peripheral resistance are associated with resistance artery dysfunction, characterized by abnormal responses to pressure, flow, and pharmacological agents such as acetylcholine and bradykinin.1–3
The cellular and molecular mechanisms that translate pressure changes to VSMC contraction have not been fully elucidated. Using mesenteric arteries, we reported a pressure-induced activation of ERK1/2 mitogen-activated protein (MAP) kinases in a tyrosine kinase–dependent manner, although the role of these signaling intermediates in pressure-induced MT was not investigated.4,5 Other studies have shown that both rho kinase and protein kinase C (PKC) are involved in pressure-induced MT in mesenteric resistance vessels.6–8 However, it is unclear how mechanical stretch activates these intracellular signaling mechanisms and therefore MT development. One potential mechanism may involve activation of cell surface receptors, because pressure and mechanical stretch have been shown to activate platelet-derived growth factor receptors in both intact vessels and cultured VSMCs.9
MT is also influenced by neurohormonal mechanisms via activation of signal transduction pathways that regulate VSMC contraction and growth.5,10,11 For example, low concentrations of Ang II potentiate MT, whereas higher Ang II concentrations induce contraction of resistance arteries.12,13 These contractile effects of Ang II are attributed largely to angiotensin II type I receptor (AT1-R) activation.4 Multiple signal transduction cascades are stimulated by AT1-R in resistance vessels and in cultured aortic VSMCs, including extracellular recognition (ERK) MAP kinases, PKC, and tyrosine kinases such as PYK2.14–16 Recent studies have indicated that transactivation of the epidermal growth factor receptor (EGFR) may be an important upstream signaling intermediate that links AT1-R to these downstream signaling cascades.17 In cultured aortic VSMCs, EGFR transactivation by AT1-R appears to involve both intracellular (src activation) and extracellular (membrane shedding of EGFR ligands) pathways.17 Moreover, it has been shown that heparin-binding EGF, which is normally bound to the cell membrane and released on cleavage by metalloproteinases, also activates EGFR.17
The EGFR is an 1186-amino-acid glycoprotein containing a single transmembrane domain, an extracellular portion involved in ligand binding, and an intracellular portion harboring the tyrosine kinase domain. Although there is a wealth of information concerning the growth-promoting effects of EGFR in cultured VSMCs, its role in the regulation of vascular function, and especially in the control resistance artery tone, has not been well defined. However, a very recent report indicates that 
1ß-adrenoreceptor agonist–induced contraction of large mesenteric artery by use of the myograph technique (400 to 500 µm of diameter) is mediated by EGFR transactivation.18 Thus, the purpose of this study was to investigate the role of EGFR transactivation in the development of MT in response to pressure changes and Ang II– and KCl-induced contraction in resistance arteries.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Functional Assessment of Resistance Artery Tone and Contractility
Mice (C57-Bl6) were obtained from Jackson Laboratories, Bar Harbor, Me. Mesenteric resistance arteries (MRAs) (mean diameter, 104±5 µm at 75 mm Hg of intraluminal pressure) were dissected, mounted onto 2 glass micropipettes in a vessel chamber, and slowly pressurized to 100 mm Hg by use of a pressure-servo-control perfusion (Living Systems Instruments, www.livingsys.com) to stretch the artery and set a constant artery length. Vessel diameter was continuously monitored by a video image analyzer as described previously.5 Cannulated arterial segments were submerged in 10 mL of physiological salt solution (pH 7.4) oxygenated with 10% O2, 5% CO2, and 85% N2. The functional integrity of the endothelial cell layer was assessed by testing the endothelium-dependent vasodilating effect of acetylcholine (1 µmol/L) after precontraction with phenylephrine (1 µmol/L). Vessels not responding by full contraction and relaxation to phenylephrine and acetylcholine, respectively, were discarded. After a 45-minute equilibration period, diameter changes were measured when intraluminal pressure was increased from 25 to 125 mm Hg. Under these conditions, MT was observed within 3 to 5 minutes. At the end of each experiment, arteries were perfused and superfused with a calcium-free physiological salt solution containing 2 mmol/L EGTA and 100 µmol/L sodium nitroprusside, and pressure steps were repeated to determine the passive diameter of the resistance arteries.
MT was investigated in MRAs under intraluminal pressure changes (25 to 125 mm Hg) and then repeated in the same artery pretreated for 30 minutes with the EGFR antagonist AG1478 (5 µmol/L) or PD1535035 (1 µmol/L). In a separate series of vessels, MT was evaluated in the absence and in the presence of either 100 ng/mL heparin, the nonspecific matrix metalloproteinase (MMP) inhibitor BB94 (Batimastat, British Biotech UK, 10 µmol/L), a MMP-2 inhibitor (1 µmol/L), an MMP-2/9 inhibitor (1 µmol/L), anti–heparin-binding EGF (HB-EGF) antibodies (1 µg/mL), 50 ng/mL EGF, or 50 ng/mL HB-EGF. On each artery, 1 drug was used and had its own control.
Pharmacology
For Ang II experiments, MRAs were maintained at 50 mm Hg of intraluminal pressure, and then a dose-response curve was investigated. To avoid desensitization to Ang II, we also used 1 dose of 100 nmol/L Ang II with or without AG1478 (5 µmol/L) or PD1535035 (1 µmol/L). For KCl, resistance arteries were maintained at 50 mm Hg, and then contraction to 60 mmol/L KCl was tested with and without AG1478 (5 µmol/L).
Metalloprotease Activity
In separate experiments, MRAs were mounted in an arteriograph and equilibrated at 25 mm Hg of intraluminal pressure for 45 minutes. After the equilibration period, the intraluminal pressure was then increased to 75 mm Hg to induce MT development, which typically was observed 3 to 5 minutes after the intraluminal pressure change. Arteries that did not develop MT were discarded. At the end of the MT development phase, resistance arteries were immediately frozen in liquid nitrogen to determine MMP activity by zymography. Control resistance arteries were isolated and equilibrated under zero pressure. MRAs were sonicated and homogenized in zymography buffer. Gelatin zymography was performed to confirm enzyme activities.19
Immunoprecipitation and Western Blot Analysis to Measure EGFR Phosphorylation
MRAs were isolated from mice, mounted in an arteriograph, and equilibrated at 25 mm Hg for 45 minutes. Resistance arteries were then stimulated at various pressures (0 to 75 mm Hg) with or without MMP-2/9 inhibition. Arteries were immediately snap-frozen in liquid nitrogen. Frozen vessel segments were pulverized and resuspended in ice-cold lysis buffer.4 All samples were immunoprecipitated with a anti–total EGFR antibody and then subjected to immunoblotting with an anti-phosphorylated EGFR antibody (1:1000, Cell Signaling Technology). Blots were stripped and reprobed with an anti–total EGFR antibody to verify gel loading.
HB-EGF Measurement
MRAs were mounted in an arteriograph and equilibrated for 45 minutes at 25 mm Hg. MRAs then were stimulated with 25 or 75 mm Hg with or without MMP-2/9 inhibition to develop MT, and the medium was harvested to determine the release of HB-EGF. Control medium was obtained from MRAs held at 0 mm Hg. Samples were incubated overnight with heparin-agarose type I beads and an HB-EGF antibody. HB-EGF was detected by immunoblotting.
Statistical Analysis
Results are expressed as mean±SEM, where n is the number of arterial segments studied. Significance of the differences between groups was determined by 1- or 2-factor ANOVA, where appropriate, followed by Bonferroni post hoc analysis (InStat). Differences were considered significant at a value of P<0.05.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
In isolated MRAs, stepwise increases in pressure induced MT development (Figure 1). To determine whether the magnitude of MT under intraluminal pressure changes is reproducible, pressure-induced MT was repeated twice with an intervening 30-minute interval. The magnitude of MT to both pressure stimuli was similar, indicating that there is no run-down with time (data not shown). MT (which is a contraction induced in response to pressure changes) was significantly decreased when the artery was treated with the EGFR inhibitor AG1478 (5 µmol/L) (Figure 1, A, C, and D). MT was inhibited in a dose-dependent manner by AG1478 (Figure 1E). These concentrations had no effect on the basal artery tone at 25 mm Hg. Similar results were observed by use of another EGFR inhibitor, PD1535035 (1 µmol/L, data not shown).
|
Using immunoprecipitation and Western blot analysis, we found that pressure-induced MT was associated with EGFR phosphorylation (Figure 1B; B1). MMP-2/9 inhibition completely inhibited EGFR phosphorylation (Figure 1B; B2).
Studies in several cell types, including cultured VSMCs from conduit arteries, indicate that EGFR transactivation by G protein–coupled receptor agonists such as Ang II is mediated by HB-EGF shedding mediated by metalloproteinase activation. To determine whether Ang II–induced contraction of mesenteric arteries involved EGFR transactivation, we first determined the effects of AG1478 on Ang II–induced contraction. A dose response to Ang II (0.1 to 100 nmol/L) was established in resistance arteries held at 50 mm Hg (Figure 2D). To avoid possible AT1-R desensitization in the Ang II dose-response studies, we also used a single dose of Ang II that elicited a biphasic contraction of MRAs (held at 50 mm Hg), consisting of a peak contraction followed by a plateau (Figure 2, A–C). Surprisingly, EGFR inhibitors had no effect on the Ang II–induced contraction. Similarly, the contraction induced by 60 mmol/L KCl was not affected by EGFR inhibition (Figure 2E).
|
The potentiation of MT by exogenous EGF (50 ng/mL) was completely blocked by 5 µmol/L AG1478 (Figure 3). Similarly, the addition of 50 ng/mL HB-EGF significantly potentiated MT (from 59.4±1% to 51.2±0.6% of passive diameter at 75 mm Hg, Figure 4A). Pretreatment of resistance arteries, with or without endothelium, with heparin (to sequester HB-EGF) or a neutralizing anti–HB-EGF (1 µg/mL) significantly decreased MT (Figure 4, B and C, respectively). Finally, HB-EGF shedding from MRAs into the medium was increased in response to MT development and completely blocked by MMP-2/9 inhibition (Figure 4D).
|
|
Recent evidence indicates that metalloproteinases may induce membrane shedding of HB-EGF. We next determined the effects of metalloproteinase inhibition on pressure-induced MT. Pretreatment with a nonspecific MMP inhibitor (BB94, 10 µmol/L) significantly decreased MT from 54±2.5% to 77±1.1% of passive diameter at 75 mm Hg compared with their respective controls (Figure 5A). MT was significantly inhibited in the presence of either MMP-2 or MMP2/9 inhibitors (1 µmol/L) (Figure 5B). Using zymography, we next confirmed that MT induced by 75 mm Hg of intraluminal pressure is associated with increased MMP2/9 activities compared with resistance arteries under 25 mm Hg or 0 pressure (Figure 6).
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The novel finding of this study is that the development of MT, which is important in the regulation of blood pressure, in response to increased intraluminal pressure involves the activation of MMPs, membrane shedding of HB-EGF, and subsequent EGFR transactivation.
A vast body of knowledge has emerged concerning the role of EGF ligands and receptors in embryonic development, physiology, and pathology.17 In cell culture, studies have already touched on the critical role of EGFR activation in Ang II–induced signaling and vascular smooth muscle growth.20 In this study, we shed light on an additional role of EGF/EGFR and show that EGFR may participate in a link between a mechanical force (pressure) and the myogenic response of resistance arteries.
The regulation of HB-EGF shedding by MMPs within the cardiovascular system has received increasing attention. For example, the release of HB-EGF by ADAM12 (metalloproteinase) was shown to play a role in hypertrophic signaling of cardiomyocytes, suggesting that inhibition of HB-EGF shedding could be a potent therapeutic strategy for cardiac hypertrophy.20,21 In our study, both EGF and HB-EGF potentiated pressure-induced MT. To determine whether pressure involves the shedding of endogenous HB-EGF, we examined the ability of heparin, a neutralizing HB-EGF antibody, a nonspecific metalloproteinase inhibitor, and MMP-2/9 inhibitors to block pressure-induced MT. We also examined the HB-EGF release under pressure-induced MT or under no MMP-2/9 inhibition. All treatments resulted in a significant inhibition of pressure-induced MT. Moreover, MT development was associated with HB-EGF release from the resistance artery wall, which is inhibited under MMP-2/9 inhibition. Thus, these results suggest a mechanism by which pressure leads to MMP-2/9 activation, HB-EGF shedding, and EGFR transactivation (Figure 7).
|
The mechanisms by which pressure activates MMPs are unknown but may involve integrins or stretch-activated channels. It is also possible that pressure could directly activate a membrane-bound MMP (eg, MT1-MMP) or the closely related metalloproteinase-disintegrins (ADAMs), a family of membrane-anchored glycoproteins that have been implicated in protein ectodomain shedding.22 Alternatively, pressure-induced MMP activation could be secondary to intracellular signaling events such as PYK2, Src, PKC, or PI-3 kinases. Although sustained increases in intraluminal pressure in ex vivo porcine carotid arteries results in an upregulation of MMP-2 and MMP-9 expression,23 the rapid time course in the present study rules out changes in gene transcription.
The downstream signaling events linking EGFR activation to VSMC contraction by intraluminal pressure changes are currently unknown. One attractive candidate is PKC, because several studies have found that PKC inhibitors block MT in cerebral arteries24 and skeletal muscle arterioles.25 Recently, Koller’s laboratory reported that p38 and ERK1/2 MAP kinase inhibitors are partially involved in pressure-induced MT in rat skeletal muscle arterioles.26 Conversely, Spurrel et al27 have shown that ERK1/2 phosphorylation is apparently dissociated from the mechanisms directly contributing to the acute myogenic contractile response. The divergences need to be clarified. These molecules are all downstream of EGFR activation in cultured VSMCs. It is unclear whether EGFR transactivation is upstream or downstream of activation of ion channels involved in MT development. Future studies will delineate the exact molecular mechanisms by which EGFR transactivation transduces pressure and the signaling pathways involved into a contractile response.
In intact resistant arteries, EGFR transactivation appears to be specific for MT, because EGFR inhibition with AG1478 or PD1535035 had no effect on Ang II– or KCl-induced contraction. These findings with Ang II were surprising in light of data from cultured VSMCs isolated from large arteries, which indicated an important role of EGFR transactivation in Ang II–induced ERK1/2 signaling and growth.28 Several groups have demonstrated that EGFR transactivation is mediated by membrane shedding of HB-EGF,20,29 and in mesangial cells, Ang II–induced HB-EGF shedding and EGFR transactivation was blocked by the MMP inhibitor batimastat.30 Recently, Hao et al18 have shown by use of large mesenteric arteries that 1b-adrenoreceptor–induced contraction involved MMP-7 and EGFR transactivation. Because these arteries do not develop MT that is characteristic of resistance arteries, these findings may reflect differences between conduit and resistance vessels.31 For example, in resistance arteries, increases in intraluminal pressure lead to contraction of smooth muscle cells (ie, MT), whereas large arteries dilate. Alternatively, these findings may reflect differences between intact vessels and cultured VSMCs or in the target functional response (contraction versus growth).
Thus, we propose the following model of MT development, in which intraluminal pressure development leads to the sequential activation of MMPs, HB-EGF, and EGFR (Figure 7). The importance of our findings lies in the fact that, in pathophysiological conditions, alterations in MMPs, HB-EGF, or EGFR may result in specific changes in resistance artery contractility and thus impaired regulation of peripheral resistance. Future studies are needed to understand the link between EGF receptor and other intracellular events that may regulate MT, such as the actin cytoskeleton, myosin light chain phosphorylation, and K+/Ca2+ influx.32,33
In conclusion, the present study provides novel and significant insight into basic mechanisms that control resistance artery response to pressure. The transactivation of EGFR by pressure leading to the MT mechanism involves metalloproteinase activation and endogenous HB-EGF release. This mechanism appears to be specific to MT, because the contractions to angiotensin and KCl are independent of EGFR transactivation. These results may identify new therapeutic targets for the control of vascular function and therefore have important implications in cardiovascular physiology and disease.
|
Acknowledgments |
|---|
This work was supported by the American Heart Association, National 0430278N (Dr Matrougui), South East Affiliate 0365217B (Dr Matrougui), and National Institutes of Health RO1-HL-56046 (Dr Lucchesi).
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
- Davis MJ, Hill MA. Signaling mechanisms underlying the vascular myogenic response. Physiol Rev. 1999; 79: 387–423.
[Abstract/Free Full Text]
- Drexler H, Hayoz D, Munzel T, Hornig B, Just H, Brunner HR, Zelis R. Endothelial function in chronic congestive heart failure. Am J Cardiol. 1992; 69: 1596–1601.[CrossRef][Medline]
[Order article via Infotrieve]
- Matrougui K, Maclouf J, Levy BI, Henrion D. Impaired nitric oxide– and prostaglandin-mediated responses to flow in resistance arteries of hypertensive rats. Hypertension. 1997; 30: 942–947.
[Abstract/Free Full Text]
- Matrougui K, Eskildsen-Helmond YE, Fiebeler A, Henrion D, Levy BI, Tedgui A, Mulvany MJ. Angiotensin II stimulates extracellular signal–regulated kinase activity in intact pressurized rat mesenteric resistance arteries. Hypertension. 2000; 36: 617–621.
[Abstract/Free Full Text]
- Matrougui K, Tanko LB, Loufrani L, Gorny D, Levy BI, Tedgui A, Henrion D. Involvement of Rho-kinase and the actin filament network in angiotensin II–induced contraction and extracellular signal–regulated kinase activity in intact rat mesenteric resistance arteries. Arterioscler Thromb Vasc Biol. 2001; 21: 1288–1293.
[Abstract/Free Full Text]
- VanBavel E, van der Meulen ET, Spaan JA. Role of Rho-associated protein kinase in tone and calcium sensitivity of cannulated rat mesenteric small arteries. Exp Physiol. 2001; 86: 585–592.[Abstract]
- Wesselman JP, Spaan JA, van der Meulen ET, VanBavel E. Role of protein kinase C in myogenic calcium-contraction coupling of rat cannulated mesenteric small arteries. Clin Exp Pharmacol Physiol. 2001; 28: 848–855.[CrossRef][Medline]
[Order article via Infotrieve]
- Bakker EN, Balt JC, Pfaffendorf M, Spaan JA, VanBavel E. Vasomotor effects of arg-gly-asp (RGD) peptides are limited and not related to endothelium-derived hyperpolarizing factor–mediated relaxation in rat mesenteric arteries. Clin Exp Pharmacol Physiol. 2001; 28: 873–876.[CrossRef][Medline]
[Order article via Infotrieve]
- Hu Y, Bock G, Wick G, Xu Q. Activation of PDGF receptor alpha in vascular smooth muscle cells by mechanical stress. FASEB J. 1998; 12: 1135–1142.
[Abstract/Free Full Text]
- Matrougui K, Loufrani L, Heymes C, Levy BI, Henrion D. Activation of AT2 receptors by endogenous angiotensin II is involved in flow-induced dilation in rat resistance arteries. Hypertension. 1999; 34: 659–665.
[Abstract/Free Full Text]
- Weber DS, Frisbee JC, Lombard JH. Selective potentiation of angiotensin-induced constriction of skeletal muscle resistance arteries by chronic elevations in dietary salt intake. Microvasc Res. 1999; 57: 310–319.[CrossRef][Medline]
[Order article via Infotrieve]
- Henrion D, Amant C, Benessiano J, Philip I, Plantefeve G, Chatel D, Hwas U, Desmont JM, Durand G, Amouyel P, Levy BI. Angiotensin II type 1 receptor gene polymorphism is associated with an increased vascular reactivity in the human mammary artery in vitro. J Vasc Res. 1998; 35: 356–362.[CrossRef][Medline]
[Order article via Infotrieve]
- Dowell FJ, Henrion D, Benessiano J, Poitevin P, Levy B. Chronic infusion of low-dose angiotensin II potentiates the adrenergic response in vivo. J Hypertens. 1996; 14: 177–182.[CrossRef][Medline]
[Order article via Infotrieve]
- Rocic P, Govindarajan G, Sabri A, Lucchesi PA. A role for PYK2 in regulation of ERK1/2 MAP kinases and PI 3-kinase by Ang II in vascular smooth muscle. Am J Physiol. 2001; 280: C90–C99.
- Rocic P, Griffin TM, McRae CN, Lucchesi PA. Altered PYK2 phosphorylation by Ang II in hypertensive vascular smooth muscle. Am J Physiol. 2002; 282: H457–H465.
- Rocic P, Lucchesi PA. Down-regulation by antisense oligonucleotides establishes a role for the proline-rich tyrosine kinase PYK2 in angiotensin II–induced signaling in vascular smooth muscle. J Biol Chem. 2001; 276: 21902–21906.
[Abstract/Free Full Text]
- Kalmes A, Daum G, Clowes AW. EGFR transactivation in the regulation of SMC function. Ann N Y Acad Sci. 2001; 947: 42–54; discussion 54–55.
- Hao L, Du M, Lopez-Campistrous A, Fernandez-Patron C. Agonist-induced activation of matrix metalloproteinase-7 promotes vasoconstriction through the epidermal growth factor-receptor pathway. Circ Res. 2004; 94: 68–76.
[Abstract/Free Full Text]
- Heo JH, Lucero J, Abumiya T, Koziol JA, Copeland BR, del Zoppo GJ. Matrix metalloproteinases increase very early during experimental focal cerebral ischemia. J Cereb Blood Flow Metab. 1999; 19: 624–633.[CrossRef][Medline]
[Order article via Infotrieve]
- Asakura M, Kitakaze M. The role of HB-EGF in angiotensin II–signaling [in Japanese]. Nippon Rinsho. 2002; 60: 1916–1921.[Medline]
[Order article via Infotrieve]
- Asakura M, Kitakaze M, Takashima S, Liao Y, Ishikura F, Yoshinaka T, Ohmoto H, Node K, Yoshino K, Ishiguro H, Asanuma H, Sanada S, Matsumura Y, Takeda H, Beppu S, Tada M, Hori M, Higashiyama S. Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: metalloproteinase inhibitors as a new therapy. Nat Med. 2002; 8: 35–40.[CrossRef][Medline]
[Order article via Infotrieve]
- Black RA, White JM. ADAMs: focus on the protease domain. Curr Opin Cell Biol. 1998; 10: 654–659.[CrossRef][Medline]
[Order article via Infotrieve]
- Chesler NC, Ku DN, Galis ZS. Transmural pressure induces matrix-degrading activity in porcine arteries ex vivo. Am J Physiol. 1999; 277: H2002–H2009.[Medline]
[Order article via Infotrieve]
- Osol G, Laher I, Cipolla M. Protein kinase C modulates basal myogenic tone in resistance arteries from the cerebral circulation. Circ Res. 1991; 68: 359–367.
[Abstract/Free Full Text]
- Hill MA, Falcone JC, Meininger GA. Evidence for protein kinase C involvement in arteriolar myogenic reactivity. Am J Physiol. 1990; 259: H1586–H1594.[Medline]
[Order article via Infotrieve]
- Massett MP, Ungvari Z, Csiszar A, Kaley G, Koller A. Different roles of PKC and MAP kinases in arteriolar constrictions to pressure and agonists. Am J Physiol. 2002; 283: H2282–H2287.
- Spurrell BE, Murphy TV, Hill MA. Intraluminal pressure stimulates MAPK phosphorylation in arterioles: temporal dissociation from myogenic contractile response. Am J Physiol. 2003; 285: H1764–H1773.
- Eguchi S, Dempsey PJ, Frank GD, Motley ED, Inagami T. Activation of MAPKs by angiotensin II in vascular smooth muscle cells: metalloprotease-dependent EGF receptor activation is required for activation of ERK and p38 MAPK but not for JNK. J Biol Chem. 2001; 276: 7957–7962.
[Abstract/Free Full Text]
- Bokemeyer D, Schmitz U, Kramer HJ. Angiotensin II–induced growth of vascular smooth muscle cells requires an Src-dependent activation of the epidermal growth factor receptor. Kidney Int. 2000; 58: 549–558.[Medline]
[Order article via Infotrieve]
- Nose A, Mori Y, Uchiyama-Tanaka Y, Kishimoto N, Maruyama K, Matsubara H, Iwasaka T. Regulation of glucose transporter (GLUT1) gene expression by angiotensin II in mesangial cells: involvement of HB-EGF and EGF receptor transactivation. Hypertens Res. 2003; 26: 67–73.[CrossRef][Medline]
[Order article via Infotrieve]
- Tanko LB, Matrougui K. Can we apply results from large to small arteries? Circ Res. 2002; 90: e68.
[Free Full Text]
- Gokina NI, Osol G. Actin cytoskeletal modulation of pressure-induced depolarization and Ca2+ influx in cerebral arteries. Am J Physiol. 2002; 282: H1410–H1420.
- Hill MA, Meininger GA. Calcium entry and myogenic phenomena in skeletal muscle arterioles. Am J Physiol. 1994; 267: H1085–H1092.[Medline]
[Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  J. Su, P. A. Lucchesi, R. A. Gonzalez-Villalobos, D. I. Palen, B. M. Rezk, Y. Suzuki, H. A. Boulares, and K. Matrougui Role of Advanced Glycation End Products With Oxidative Stress in Resistance Artery Dysfunction in Type 2 Diabetic Mice Arterioscler. Thromb. Vasc. Biol., August 1, 2008; 28(8): 1432 - 1438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Belmadani, M. Zerfaoui, H. A. Boulares, D. I. Palen, and K. Matrougui Microvessel vascular smooth muscle cells contribute to collagen type I deposition through ERK1/2 MAP kinase, {alpha}v{beta}3-integrin, and TGF-{beta}1 in response to ANG II and high glucose Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H69 - H76. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Belmadani, D. I. Palen, R. A. Gonzalez-Villalobos, H. A. Boulares, and K. Matrougui Elevated Epidermal Growth Factor Receptor Phosphorylation Induces Resistance Artery Dysfunction in Diabetic db/db Mice Diabetes, June 1, 2008; 57(6): 1629 - 1637. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Schubert, D. Lidington, and S.-S. Bolz The emerging role of Ca2+ sensitivity regulation in promoting myogenic vasoconstriction Cardiovasc Res, January 1, 2008; 77(1): 8 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sachidanandam, V. Portik-Dobos, A. K. Harris, J. R. Hutchinson, E. Muller, M. H. Johnson, and A. Ergul Evidence for Vasculoprotective Effects of ETB Receptors in Resistance Artery Remodeling in Diabetes Diabetes, November 1, 2007; 56(11): 2753 - 2758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Koide, P. L. Penar, B. I. Tranmer, and G. C. Wellman Heparin-binding EGF-like growth factor mediates oxyhemoglobin-induced suppression of voltage-dependent potassium channels in rabbit cerebral artery myocytes Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1750 - H1759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhou, B. O. Ibe, and J. U. Raj Platelet-activating factor induces ovine fetal pulmonary venous smooth muscle cell proliferation: role of epidermal growth factor receptor transactivation Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2773 - H2781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Paravicini and R. M. Touyz Redox signaling in hypertension Cardiovasc Res, July 15, 2006; 71(2): 247 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Grantcharova, H. P. Reusch, S. Grossmann, J. Eichhorst, H.-W. Krell, M. Beyermann, W. Rosenthal, and A. Oksche N-Terminal Proteolysis of the Endothelin B Receptor Abolishes Its Ability to Induce EGF Receptor Transactivation and Contractile Protein Expression in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1288 - 1296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Shukla, T. F. Barrett, K. I. Nakayama, K. Nakayama, B. T. Mossman, and K. M. Lounsbury Transcriptional up-regulation of MMP12 and MMP13 by asbestos occurs via a PKC{delta}-dependent pathway in murine lung FASEB J, May 1, 2006; 20(7): 997 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Newby Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates Cardiovasc Res, February 15, 2006; 69(3): 614 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ivanov, V. Gerzanich, S. Ivanova, R. DenHaese, O. Tsymbalyuk, and J. M. Simard Adenylate cyclase 5 and KCa1.1 channel are required for EGFR up-regulation of PCNA in native contractile rat basilar artery smooth muscle J. Physiol., January 1, 2006; 570(1): 73 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. I. Palen, S. Belmadani, P. A. Lucchesi, and K. Matrougui Role of SHP-1, Kv.1.2, and cGMP in nitric oxide-induced ERK1/2 MAP kinase dephosphorylation in rat vascular smooth muscle cells Cardiovasc Res, November 1, 2005; 68(2): 268 - 277. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||