The role of protein-tyrosine phosphorylation and gelatinase production in the migration and proliferation of smooth muscle cells

Uzui, Hiroyasu; Lee, Jong–Dae; Shimizu, Hiromasa; Tsutani, Hiroshi; Ueda, Takanori

doi:10.1016/s0021-9150(99)00295-6

Cited by 76 publications

(77 citation statements)

References 32 publications

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“…It has been reported that the migration and proliferation of VSMCs, which contribute to the morphogenesis of atherosclerotic plaques, require the ECM remodelling caused by MMPs (2). The production of MMPs in VSMCs is known to be regulated by a number of cytokines and growth factors, such as platelet-derived growth factor secreted by platelets and vascular cells (1,11,18). Among the MMPs, MMP-2 has the widest distribution and plays an important role in the turnover of basement membrane type IV collagen and in controlling cell proliferation (19).…”

Section: Discussionmentioning

confidence: 99%

“…Rat aortic SMCs were isolated by enzymatic digestion from the thoracic aorta of six-week-old male Sprague-Dawley rats (Charles River, Japan) as described previously (11). All surgical interventions and anesthesia were conducted in conformity with institutional guidelines and in compliance with international laws and policies (12,13).…”

Section: Preparation Of Smcsmentioning

confidence: 99%

“…After treatments for 24 h, 48 h and 72 h, medium samples were harvested, centrifuged at 2000 g for 10 min and normalized for cell protein content using the Bio-Rad assay (Bio-Rad Laboratories, USA) (11). The samples were applied without reduction to a 7.5% polyacrylamide slab gel impregnated with 1 mg/mL gelatin (15).…”

Section: Analysis Of Gelatinase Productionmentioning

confidence: 99%

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Effects of heparin on the production of homocysteine-induced extracellular matrix metalloproteinase-2 in cultured rat vascular smooth muscle cells

Guo

Lee

Uzui

et al. 2007

Canadian Journal of Cardiology

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Section: Discussionmentioning

confidence: 99%

Section: Preparation Of Smcsmentioning

confidence: 99%

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Effects of heparin on the production of homocysteine-induced extracellular matrix metalloproteinase-2 in cultured rat vascular smooth muscle cells

Guo

Lee

Uzui

et al. 2007

Canadian Journal of Cardiology

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“…12 All surgical interventions and anesthesia were conducted in conformity with institutional guidelines and in compliance with international laws and policies (EEC Council Directive 86/609, OJL 358, December 1987; Guide for the care and use of laboratory animals, NIH publication No. 1985).…”

Section: Preparation Of Vsmcsmentioning

confidence: 99%

Effects of Folic Acid and Magnesium on the Production of Homocysteine-Induced Extracellular Matrix Metalloproteinase-2 in Cultured Rat Vascular Smooth Muscle Cells

Guo

Lee

Uzui

et al. 2006

Circ J

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igration of vascular smooth muscle cells (VSMCs) into the vascular intima and their subsequent proliferation and remodeling of the extracellular matrix are important events in the pathogenesis of atherosclerosis. These events are regulated by various cytokines and growth factors secreted by platelets and vascular cells. 1 Zempo et al reported that the processes of migration and proliferation of VSMCs that contribute to the morphogenesis of atherosclerotic plaque require extracellular matrix remodeling induced by matrix metalloproteinases (MMPs). 2 Brown et al identified MMPs in human coronary atherosclerotic lesions and suggested that MMPs are closely related to the progression of atherosclerosis. 3 Homocysteine is an intermediate sulfur-containing amino acid formed during the intracellular metabolism of methionine. Circulating homocysteine can be increased by a genetic deficiency of the enzymatic pathways involved in Circulation Journal Vol.70, January 2006 its catabolism, as well as by environmental factors including nutritional deficiencies, life style, physiological conditions, drugs and some diseases, which mainly induce a deficiency of folic acid and vitamins B12 and B6. Therefore, the plasma homocysteine level can be reduced by interventional therapy with folic acid and vitamin B12. 4 Hyperhomocysteinemia is an independent risk factor for coronary artery disease (CAD). 5 Magnesium has been implicated in the negative correlation between cardiovascular disease and hardness of drinking water. 6 Dietary deficiency of magnesium augmented atherogenesis markedly in experimental animals fed a high cholesterol diet, and oral supplementation of magnesium to the same animals lowered serum lipid levels and attenuated the atherosclerotic process. 7 Our previous studies demonstrated that the magnesium status of men and women with variant angina is closely related to disease activity and that the intracellular magnesium level decreased in patients with cardiac syndrome X. 8-10 However, Liao et al indicated that the association of low serum and dietary magnesium with the incidence of coronary heart disease may not be causal, because the results of their prospective study differed between men and women. 11 However, the effects of magnesium, which is a natural calcium antagonist, and folic acid on homocysteine-in- Effects of Folic Acid and Magnesium on the Production of Homocysteine-Induced Extracellular Matrix Metalloproteinase-2 in Cultured Rat Vascular Smooth Muscle CellsHangyuan Guo, MD, PhD* , **; Jong-Dae Lee, MD**; Hiroyasu Uzui, MD**; Hong Yue, MD**; Junbo Wang, MD**; Kiyohiro Toyoda, MD**; Tooru Geshi, MD**; Takanori Ueda, MD** Background Hyperhomocysteinemia is an independent risk factor of coronary artery disease, but some studies have shown that patients with hyperhomocysteinemia are not prone to atherosclerosis. The aim of this study was to test whether homocysteine increases the production of matrix metalloproteinase-2 (MMP-2) and if extracellular additional magnesium and folic acid alters MMP-2 secreti...

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“…MMP inhibitors significantly reduce VSMC migration into intima, suggesting a functional role for these proteases in the vascular pathology. Uzui et al (37) showed that MMP-2 is required for VSMCs to penetrate the basal lamina barrier.…”

Section: Discussionmentioning

confidence: 99%

Conditional expression of type 2 angiotensin II receptor in rat vascular smooth muscle cells reveals the interplay of the angiotensin system in matrix metalloproteinase 2 expression and vascular remodeling

Tao

Wang²,

Srivenugopal³

et al. 2009

Int J Mol Med

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Abstract. Angiotensin II is well implicated in neointimal proliferation and the resulting restenosis, however, the mechanisms involved remain unclear. The type 2 angiotensin II (AT2) receptor, largely unexpressed in the adult vasculature, however, appears at significant levels after vascular injury. To investigate the specific contribution of AT2 receptor and the interplay of the angiotensin system to neointima, we engineered rat vascular smooth muscle cells (VSMCs) to express the AT2 receptor in a tetracycline-regulated system. Several VSMC clones resistant to both hygromycin and G418 were selected, many of which showed high, but regulatable levels of AT2R expression within 48 h of doxycycline (Dox) exposure. In untransfected VSMCs and stable transfectants with no AT2R induction, Ang II significantly increased the expression of matrix metalloproteinase 2 (MMP-2), which is linked to neointimal growth. However, induction of AT2R by Dox addition markedly decreased MMP-2 levels (P<0.01) and this downregulation was further promoted by CV-11974, a specific antagonist of AT1 receptor. In contrast, the PD123319 compound, which selectively curtails the AT2 receptor, reversed the inhibition caused by CV-11974. We conclude that Ang II enhances the MMP-2 expression via AT1R, and that enforces AT2R inhibited the same. These data confirm that AT2R functions to downregulate the effects elicited by Ang II + AT1R signaling and point to the role of MMP and extracellular matrix in vascular injury. The findings provide fresh experimental approaches to prevent or control restenosis through transduction of VSMCs expressing optimal levels of AT2R.

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The role of protein-tyrosine phosphorylation and gelatinase production in the migration and proliferation of smooth muscle cells

Cited by 76 publications

References 32 publications

Effects of heparin on the production of homocysteine-induced extracellular matrix metalloproteinase-2 in cultured rat vascular smooth muscle cells

Effects of heparin on the production of homocysteine-induced extracellular matrix metalloproteinase-2 in cultured rat vascular smooth muscle cells

Effects of Folic Acid and Magnesium on the Production of Homocysteine-Induced Extracellular Matrix Metalloproteinase-2 in Cultured Rat Vascular Smooth Muscle Cells

Conditional expression of type 2 angiotensin II receptor in rat vascular smooth muscle cells reveals the interplay of the angiotensin system in matrix metalloproteinase 2 expression and vascular remodeling

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