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

The renin-angiotensin system contributes to atherogenesis. Matrix metalloproteinases (MMP) are thought to participate in plaque destabilization through degradation of extracellular matrix. This study tested whether angiotensin II (ANG II) induces MMP in human vascular smooth muscle cells (SMC). ANG II induced expression of MMP-1, -3, and -9, but not of MMP-2 in SMC. The expression of MMP-1, a key enzyme for collagen degradation, was studied in detail. SMC stimulated with ANG II concentration-dependently released enzymatically active MMP-1. The ANG II type 1 receptor antagonists losartan and candesartan blocked ANG-II-induced MMP-1 release. Inhibition experiments with actinomycin D suggest ANG-II-induced MMP-1 mRNA regulation at the transcriptional level. Decoy oligodeoxynucleotides against nuclear factor-ĸB and activator protein 1 inhibited MMP-1 secretion, demonstrating participation of these transcription factors in MMP-1 transcription. Stimulation of MMP-1 by ANG II depended on cyclooxygenase 2. The antioxidants pyrrolidine dithiocarbamate and N-acetylcysteine, the flavin protein inhibitor diphenylene iodonium, and the NADP(H) oxidase inhibitor apocynin blocked MMP-1 release, suggesting a redox-sensitive mechanism involving NADP(H) oxidase. The reactive oxygen species (ROS) donor 2,3-dimethoxy-1,4-naphthoquinone induced MMP-1 secretion and enhanced ANG-II-stimulated MMP-1 expression. These findings indicate that ROS may increase their own production by activation of NADP(H) oxidase. The capability of ANG II to induce functionally active MMP in human SMC may contribute to the altered plaque composition seen in complicated stages of atherosclerosis.

[1]  P. López-Jaramillo,et al.  Angiotensin II-induced MMP-2 release from endothelial cells is mediated by TNF-α , 2004 .

[2]  R. Muraro,et al.  Blockade of the Angiotensin II Type 1 Receptor Stabilizes Atherosclerotic Plaques in Humans by Inhibiting Prostaglandin E2–Dependent Matrix Metalloproteinase Activity , 2004, Circulation.

[3]  R. Visse,et al.  This Review Is Part of a Thematic Series on Matrix Metalloproteinases, Which Includes the following Articles: Matrix Metalloproteinase Inhibition after Myocardial Infarction: a New Approach to Prevent Heart Failure? Matrix Metalloproteinases in Vascular Remodeling and Atherogenesis: the Good, the Ba , 2022 .

[4]  Norman Honbo,et al.  A functional activating protein 1 (AP-1) site regulates matrix metalloproteinase 2 (MMP-2) transcription by cardiac cells through interactions with JunB-Fra1 and JunB-FosB heterodimers. , 2003, The Biochemical journal.

[5]  F. Pieruzzi,et al.  ANG II increases TIMP-1 expression in rat aortic smooth muscle cells in vivo. , 2003, American journal of physiology. Heart and circulatory physiology.

[6]  B. Greenberg,et al.  Molecular Medicine Tumor Necrosis Factor-�–Induced AT 1 Receptor Upregulation Enhances Angiotensin II–Mediated Cardiac Fibroblast Responses That Favor Fibrosis , 2022 .

[7]  C. Ferrario,et al.  Mechanisms linking angiotensin II and atherogenesis , 2002, Current opinion in lipidology.

[8]  J. Mehta,et al.  Modulation of Matrix Metalloproteinase-1, Its Tissue Inhibitor, and Nuclear Factor-&kgr;B by Losartan in Hypercholesterolemic Rabbits , 2002, Journal of cardiovascular pharmacology.

[9]  M. Böhm,et al.  Effect of ramipril and furosemide treatment on interstitial remodeling in post-infarction heart failure rat hearts. , 2002, Journal of molecular and cellular cardiology.

[10]  G. Karakiulakis,et al.  Losartan Inhibits the Angiotensin II–Induced Modifications on Fibrinolysis and Matrix Deposition by Primary Human Vascular Smooth Muscle Cells , 2001, Journal of cardiovascular pharmacology.

[11]  J. Rutter,et al.  Synergistic induction of matrix metalloproteinase 1 by interleukin-1alpha and oncostatin M in human chondrocytes involves signal transducer and activator of transcription and activator protein 1 transcription factors via a novel mechanism. , 2001, Arthritis and rheumatism.

[12]  L. Oberley,et al.  H2O2-induced O⨪2Production by a Non-phagocytic NAD(P)H Oxidase Causes Oxidant Injury* , 2001, The Journal of Biological Chemistry.

[13]  F. Spinale,et al.  Matrix metalloproteinase expression and activity in isolated myocytes after neurohormonal stimulation. , 2001, American journal of physiology. Heart and circulatory physiology.

[14]  A. Newby,et al.  Inhibition of transcription factor NF-kappaB reduces matrix metalloproteinase-1, -3 and -9 production by vascular smooth muscle cells. , 2001, Cardiovascular research.

[15]  Kukin Ml.  The Heart Outcomes Prevention Evaluation Study. , 2001, Current cardiology reports.

[16]  M. Nishino,et al.  Increased Angiotensin-Converting Enzyme Activity in Coronary Artery Specimens From Patients With Acute Coronary Syndrome , 2001, Circulation.

[17]  R. Brandes,et al.  The terminal complement complex C5b‐9 stimulates interleukin‐6 production in human smooth‐muscle cells through activation of transcription factors NF‐κB and AP‐1 , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[18]  K. Schmidt-Ott,et al.  The multiple actions of angiotensin II in atherosclerosis , 2000, Regulatory Peptides.

[19]  T. Bocan,et al.  MMP/TIMP expression in spontaneously hypertensive heart failure rats: the effect of ACE- and MMP-inhibition. , 2000, Cardiovascular research.

[20]  W. Kübler,et al.  Endothelin-1 induces interleukin-6 release via acctivation of the transcription factor NF-κB in human vascular smooth muscle cells , 2000, Basic Research in Cardiology.

[21]  W Kübler,et al.  Differential activation of mitogen-activated protein kinases in smooth muscle cells by angiotensin II: involvement of p22phox and reactive oxygen species. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[22]  S. Yusuf,et al.  Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. , 2000 .

[23]  S. Yusuf,et al.  Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000;342:145-53. , 2000 .

[24]  K. Ohnaka,et al.  Induction of cyclooxygenase-2 by angiotensin II in cultured rat vascular smooth muscle cells. , 2000, Hypertension.

[25]  Ashutosh Kumar Singh,et al.  Role of angiotensin II in glucose-induced inhibition of mesangial matrix degradation. , 1999, Diabetes.

[26]  J. Pickering,et al.  Angiotensin II stimulates collagen synthesis in human vascular smooth muscle cells. Involvement of the AT(1) receptor, transforming growth factor-beta, and tyrosine phosphorylation. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[27]  P. Libby,et al.  Angiotensin induces inflammatory activation of human vascular smooth muscle cells. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[28]  P. Libby,et al.  Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human atheromatous plaques. , 1999, Circulation.

[29]  W. Kübler,et al.  Angiotensin II activates the proinflammatory transcription factor nuclear factor-kappaB in human monocytes. , 1999, Biochemical and biophysical research communications.

[30]  M. Runge,et al.  Angiotensin II induces interleukin-6 transcription in vascular smooth muscle cells through pleiotropic activation of nuclear factor-kappa B transcription factors. , 1999, Circulation research.

[31]  L. Arroyo,et al.  Mechanisms of plaque rupture: mechanical and biologic interactions. , 1999, Cardiovascular research.

[32]  R. Alexander,et al.  Angiotensin II induces monocyte chemoattractant protein-1 gene expression in rat vascular smooth muscle cells. , 1998, Circulation research.

[33]  D. Kass,et al.  Synergistic exacerbation of diastolic stiffness from short-term tachycardia-induced cardiodepression and angiotensin II. , 1998, Circulation research.

[34]  D. Harrison,et al.  Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. , 1996, The Journal of clinical investigation.

[35]  K. Weber,et al.  Role of angiotensin II and prostaglandin E2 in regulating cardiac fibroblast collagen turnover. , 1995, The American journal of cardiology.

[36]  P. Libby.  Molecular bases of the acute coronary syndromes. , 1995, Circulation.

[37]  P. Libby,et al.  Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[38]  S. Orrenius,et al.  Different prooxidant levels stimulate growth, trigger apoptosis, or produce necrosis of insulin-secreting RINm5F cells. The role of intracellular polyamines. , 1994, The Journal of biological chemistry.

[39]  P. Libby,et al.  Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. , 1994, The Journal of clinical investigation.

[40]  G. Lamas,et al.  Effects of captopril on ischemic events after myocardial infarction. Results of the Survival and Ventricular Enlargement trial. SAVE Investigators. , 1994, Circulation.

[41]  P. Libby,et al.  Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. , 1994, Circulation research.

[42]  T. Resink,et al.  Activation of human peripheral monocytes by angiotensin II , 1994, FEBS letters.

[43]  R W Alexander,et al.  Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. , 1994, Circulation research.

[44]  Salim Yusuf,et al.  Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. , 1991, The New England journal of medicine.

[45]  A. Gown,et al.  HHF35, a muscle actin-specific monoclonal antibody. II. Reactivity in normal, reactive, and neoplastic human tissues. , 1987, The American journal of pathology.

[46]  P. Libby,et al.  Culture of quiescent arterial smooth muscle cells in a defined serum‐free medium , 1983, Journal of cellular physiology.