Angiotensin II Stimulates Matrix Metalloproteinase Secretion in Human Vascular Smooth Muscle Cells via Nuclear Factor-κB and Activator Protein 1 in a Redox-Sensitive Manner

Browatzki, Michael; Larsen, Dina; Pfeiffer, C; Gehrke, Sven G.; Schmidt, Joachim; Kranzhöfer, Alexander; Katus, Hugo A.; Kranzhöfer, Roger

doi:10.1159/000087451

Cited by 125 publications

(100 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Expression of MMP-1, -3, and -9 is increased in human vascular smooth muscle cells exposed to Ang II, 21 and MMP-2 expression and activity are induced by Ang II in human endothelial cells 22 and in mouse vascular smooth muscle cells. 23 Furthermore, nonhypertensive doses of Ang II were found to induce MMP-2 in young rat arteries in vivo.…”

Section: Discussionmentioning

confidence: 91%

Role of Matrix Metalloproteinases in Early Hypertensive Vascular Remodeling

Flamant

Placier²,

Dubroca³

et al. 2007

Hypertension

158

View full text Add to dashboard Cite

Abstract-Hypertension is associated with vascular remodeling characterized by rearrangement of extracellular matrix proteins. To evaluate how matrix metalloproteinase (MMP)-9 contributes to the progression of hypertensive vascular disease in vivo, wild-type (wt) or MMP-9 Ϫ/Ϫ mice were treated with angiotensin II (Ang II; 1 g/kg per minute, by minipump) plus a 5% NaCl diet during 10 days. Baseline blood pressure was equivalent in wt and knockout mice, but Ang II treatment increased systolic blood pressure to a greater extent (PϽ0.05) in MMP-9 Ϫ/Ϫ mice (94Ϯ6 to 134Ϯ6 mm Hg; PϽ0.001) than in wt animals (93Ϯ4 to 114Ϯ6 mm Hg; PϽ0.01). In wt mice, Ang II treatment increased the carotid artery pressure-diameter relationship significantly, and maximal diameter reached 981Ϯ19 m (PϽ0.01 versus sham; 891Ϯ10 m). In contrast, in MMP-9 Ϫ/Ϫ mice, carotid artery compliance was actually reduced after Ang II (PϽ0.05), and maximal diameter only reached 878Ϯ13 m. Ang II treatment induced MMP-2 and increased carotid media thickness equally in both phenotypes. However, MMP-9 induction and in situ gelatinase activity were only enhanced in Ang II-treated wt mice, and vessels from these mice also produced more collagen I breakdown products than their MMP-9 Ϫ/Ϫ counterparts (PϽ0.05). Inversely, staining for collagen IV was particularly enhanced in vessels from MMP-9 Ϫ/Ϫ mice treated with Ang II. These results demonstrate the following: (1) the onset of Ang II-induced hypertension is accompanied by increased MMP-9 activity in conductance vessels; (2) absence of MMP-9 activity results in vessel stiffness and increased pulse pressure; and (3) MMP-9 activation is associated with a beneficial role early on in hypertension by preserving vessel compliance and alleviating blood pressure increase. Key Words: angiotensin Ⅲ metalloproteinases Ⅲ remodeling Ⅲ hypertension Ⅲ collagen B lood pressure is a major determinant of vessel wall structure and composition. Any change in strain will generate counteracting radial and tangential forces that drive transformations in the vessel wall to accommodate the new pressure setting and restore basal levels of tensile stress. 1 It therefore follows that a key characteristic of hypertensive conductance arteries is increased wall thickness accompanied by enhanced rigidity. In hypertensive patients, this is manifest by elevated pulse wave velocity, an independent predictor of mortality in patients with end-stage renal failure, hypertension, and diabetes, as well as in older individuals. 2 Nevertheless, using an ex vivo model of carotid artery, we have shown recently that early vascular remodeling in the hypertensive context is actually associated with increased conductance vessel distensibility rather than rigidity. 3 In fact, results from our own laboratory 3 and others 4 -8 have shown that exposing arteries or vascular cells to stretch induces the release of matrix metalloproteinases (MMPs). This perplexing observation led us to hypothesize that increased compliance may be an early compensatory mechanism allowi...

show abstract

Section: Discussionmentioning

confidence: 91%

Role of Matrix Metalloproteinases in Early Hypertensive Vascular Remodeling

Flamant

Placier²,

Dubroca³

et al. 2007

Hypertension

158

View full text Add to dashboard Cite

show abstract

“…Both MMP-2 and MMP-9 are induced by ROS (Luchtefeld et al 2005). Expression of another MMP, MMP-1, which is important in collagen degradation, is increased by Ang II stimulation through NF-κB and activating protein-1 (AP-1) (Browatzki et al 2005). TNFα stimulation has similar effects (Browatzki et al 2005).…”

Section: Vascular Smooth Muscle Cell Migrationmentioning

confidence: 99%

“…Expression of another MMP, MMP-1, which is important in collagen degradation, is increased by Ang II stimulation through NF-κB and activating protein-1 (AP-1) (Browatzki et al 2005). TNFα stimulation has similar effects (Browatzki et al 2005). Moreover, MMP-7, a MMP with high degradative ability, is also activated by ROS,specifically hypochloric acid (HOCl − ) (Fu et al 2001).…”

Section: Vascular Smooth Muscle Cell Migrationmentioning

confidence: 99%

Basic Mechanisms of Oxidative Stress and Reactive Oxygen Species in Cardiovascular Injury

Papaharalambus

Griendling

2007

Trends in Cardiovascular Medicine

292

224

View full text Add to dashboard Cite

The development of vascular disease has its origins in an initial insult to the vessel wall by biological or mechanical factors. The disruption of homeostatic mechanisms leads to alteration of the original architecture of the vessel and its biological responsiveness, contributing to acute or chronic diseases such as stroke, hypertension and atherosclerosis. Endothelial dysfunction, macrophage infiltration of the vessel wall, and proliferation and migration of smooth muscle cells all involve different types of reactive oxygen species, produced by various vessel wall components. Although basic science and animal research have clearly established the role of reactive oxygen species in the progression of vascular disease, the failure of clinical trials with antioxidant compounds has underscored the need for better antioxidant therapies and a more thorough understanding of the role of reactive oxygen species in cardiovascular physiology and pathology.The fundamental processes underlying the development of vascular diseases such as atherosclerosis, restenosis and hypertensive vascular remodeling have their origins in an initial insult to the vessel wall. Such an insult may arise from mechanical disruption that occurs during percutaneous coronary angioplasty or at regions of oscillatory shear stress, or it can result from biological causes, such as hypercholesterolemia, excess free radicals, diabetes, increased concentrations of plasma homocysteine, or infectious agents. Injury promotes disruption of the homeostatic mechanisms of the endothelial protective barrier, changing its natural properties, increasing its adhesiveness to leukocytes and altering its permeability. This endothelial dysfunction also leads to the formation of vasoactive molecules, which in turn induce inflammatory genes, inactivate nitric oxide (NO • ) and its protective functions, and activate matrix metalloproteinases, leading to extracellular matrix remodeling, and increased smooth muscle cell (VSMC) growth, migration and proliferation. Each of these processes contributes to thickening of the vessel wall or the formation of lesions that can lead to hypertension, acute myocardial infarction and stroke. Reactive Oxygen Species and Vascular InjuryIn the past decade a staggering amount of evidence implicates a common denominator, reactive oxygen species (ROS), in the development of most cardiovascular diseases (Figure 1). Superoxide (O 2 •− ) and hydrogen peroxide (H 2 O 2 ) are two of the most biologically important ROS in the cardiovascular system, and are produced in vascular cells by a number of oxidases, including the NADPH oxidases (Nox) and xanthine oxidase, lipoxygenases, cytochrome p450,

show abstract

“…Studies (5,9,13,29,46) have shown that ANG II induces cardiac remodeling through an upregulation of MMP activity. We examined the expression of MMPs in cardiac tissue by real-time PCR and evaluated MMP activity by zymography.…”

Section: Cardiac Expression and Activity Of Mmpsmentioning

confidence: 99%

Air pollution and cardiac remodeling: a role for RhoA/Rho-kinase

Zhao¹,

Yue²,

Xu³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

110

View full text Add to dashboard Cite

Exposure to ambient air pollution has been associated with increases in blood pressure. We have previously demonstrated activation of the Rho/Rho kinase pathway in experimental hypertension in rats. In this investigation, we evaluated the effects of particulate matter of Ͻ2.5 m (PM2.5) exposure on cardiovascular responses and remodeling and tested the effect of Rho kinase inhibition on these effects. C57BL/6 mice were exposed to concentrated ambient PM2.5 or filtered air for 12 wk followed by a 14-day ANG II infusion in conjunction with fasudil, a Rho kinase antagonist, or placebo treatment. Blood pressure was monitored, followed by analysis of vascular function and ventricular remodeling indexes. PM 2.5 exposure potentiated ANG II-induced hypertension, and this effect was abolished by fasudil treatment. Cardiac and vascular RhoA activation was enhanced by PM 2.5 exposure along with increased expression of the guanine exchange factors (GEFs) PDZRhoGEF and p115 RhoGEF in PM 2.5-exposed mice. Parallel with increased RhoA activation, PM 2.5 exposure increased ANG II-induced cardiac hypertrophy and collagen deposition, with these increases being normalized by fasudil treatment. In conclusion, PM2.5 potentiates cardiac remodeling in response to ANG II through RhoA/ Rho kinase-dependent mechanisms. These findings have implications for the chronic cardiovascular health effects of air pollution. hypertension; vasoconstrictors; angiotensin II AMBIENT AIR POLLUTION mediated by fine particulate matter (PM) of Ͻ2.5 m in aerodynamic diameter (PM 2.5 ) has been associated with adverse cardiovascular outcomes (8,31,39,49). One important mechanism is the elevation in blood pressure (BP) that may occur within hours to days after exposure to high concentrations of PM 2.5 (6,16,21,52). Recent studies (21, 58) have shown that commonly encountered levels of airborne pollutants can result in a prohypertensive response in humans that may be exaggerated in predisposed individuals. This potentiating effect of inhaled particulates has been noted with other chronic conditions or risk factors such as atherosclerosis, diabetes, and postmenopausal status (31,40,49). Although the precise mechanisms remain elusive, there is increasing evidence that PM 2.5 exposure results in rapid changes in the vasculature (7, 32). We (51) have previously shown that PM 2.5 exposure results in the activation of RhoA/Rho-kinase (ROCK) through ROS pathways and hypothesized that this important signaling cascade may mediate at least some of the prohypertensive effects of PM 2.5 . Given the important role of RhoA/ ROCK in a multitude of processes, including the regulation of smooth muscle tone, cellular migration, and hypertrophy (36,47), in the present study we examined the effect of PM 2.5 exposure on vascular function and cardiac remodeling and tested the effects of ROCK antagonism.

show abstract

Angiotensin II Stimulates Matrix Metalloproteinase Secretion in Human Vascular Smooth Muscle Cells via Nuclear Factor-κB and Activator Protein 1 in a Redox-Sensitive Manner

Cited by 125 publications

References 68 publications

Role of Matrix Metalloproteinases in Early Hypertensive Vascular Remodeling

Role of Matrix Metalloproteinases in Early Hypertensive Vascular Remodeling

Basic Mechanisms of Oxidative Stress and Reactive Oxygen Species in Cardiovascular Injury

Air pollution and cardiac remodeling: a role for RhoA/Rho-kinase

Contact Info

Product

Resources

About