Atherosclerosis and proteinase activation

Dollery, C; Libby, Peter

doi:10.1016/j.cardiores.2005.11.003

Cited by 225 publications

(196 citation statements)

References 122 publications

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“…Altered expression and activity of MMP-9 and its major endogenous inhibitor, the tissue inhibitor of MMPs (TIMP)-1, have been implicated in atherosclerotic vascular remodeling. 3 In fact, experimental and clinical studies have clearly shown that MMP-9 is highly expressed in the atherosclerotic plaques, 4,5 and elevated MMP-9 levels have been shown in patients with atherosclerotic diseases. 6,7 Importantly, functional genetic polymorphisms in the MMP-9 gene modify MMP-9 levels and prognosis of patients with cardiovascular diseases.…”

Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese children

et al. 2011

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Objective: Matrix metalloproteinase-9 (MMP-9) is involved in the atherosclerotic process and functional polymorphisms in the MMP-9 gene affect MMP-9 expression/activity, and are associated with cardiovascular diseases. However, no study has tested the hypothesis that functional MMP-9 polymorphisms could affect MMP-9 levels in obese children. We investigated whether three MMP-9 gene polymorphisms (C-1562T (rs3918242), 90(CA) (14À24) (rs2234681) and Q279R (rs17576)), or haplotypes, affect MMP-9 levels in obese children. Methods: We studied 175 healthy control children and 127 obese children. Plasma MMP-9, tissue inhibitor of MMPs (TIMP)-1 and adiponectin concentrations were measured using enzyme-linked immunosorbent assay. Results: We found similar MMP-9 genotypes, allelic and haplotypes distributions in the two study groups (P40.05). However, we found lower plasma MMP-9 concentrations in obese subjects carrying the CC or the QQ genotypes for the C-1562T and the Q279R polymorphisms, respectively, in obese children compared with children with the other genotypes, or with non-obese children with the same genotypes (all Po0.05). Moreover, we found lower MMP-9 levels and lower MMP-9/TIMP-1 ratios (which reflect net MMP-9 activity) in obese children carrying the H2 haplotype (which combines the C, H and Q alleles for the three polymorphisms, respectively) when compared with obese children carrying the other haplotypes, or with non-obese children carrying the same haplotype (Po0.05). Conclusions: Our findings show that MMP-9 genotypes and haplotypes affect MMP-9 levels in obese children and adolescents, and suggest that genetic factors may modify relevant pathogenetic mechanisms involved in the development of cardiovascular complications associated with obesity in childhood.

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Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese children

et al. 2011

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“…Important among its many activities, TNF-α promotes the proliferation of smooth muscle cells (SMCs) [15] and it stimulates matrix metalloproteinase (MMP) production [6]. Thinning of the fibrous cap by MMPs is undesirable due to the release of sequestered factors that leads to thrombosis [15].…”

Section: Introductionmentioning

confidence: 99%

Lysyl oxidase propeptide inhibits smooth muscle cell signaling and proliferation

Hurtado

Vora

Sume

et al. 2008

Biochemical and Biophysical Research Communications

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Lysyl oxidase is required for the normal biosynthesis and maturation of collagen and elastin. It is expressed by vascular smooth muscle cells, and its increased expression has been previously found in atherosclerosis and in models of balloon angioplasty. The lysyl oxidase propeptide (LOX-PP) has more recently been found to have biological activity as a tumor suppressor, and it inhibits Erk1/2 Map kinase activation. We reasoned that LOX-PP may have functions in normal non-transformed cells. We, therefore, investigated its effects on smooth muscle cells, focusing on important biological processes mediated by Erk1/2-dependent signaling pathways including proliferation and matrix metalloproteinase-9 (MMP-9) expression. In addition, we investigated whether evidence for accumulation of LOX-PP could be found in vivo in a femoral artery injury model. Recombinant LOX-PP was expressed and purified, and was found to inhibit primary rat aorta smooth muscle cell proliferation and DNA synthesis by more than 50%. TNF-α-stimulated MMP-9 expression and Erk1/2 activation were both significantly inhibited by LOX-PP. Immunohistochemistry studies carried out with affinity purified anti-LOX-PP antibody showed that LOX-PP epitopes were expressed at elevated levels in vascular lesions of injured arteries. These novel data suggest that LOX-PP may provide a feedback control mechanism that serves to inhibit properties associated with the development of vascular pathology.Tumor necrosis factor-α (TNF-α) contributes to the development of atherosclerotic lesions [15]. Important among its many activities, TNF-α promotes the proliferation of smooth muscle cells (SMCs) [15] and it stimulates matrix metalloproteinase (MMP) production [6]. Thinning of the fibrous cap by MMPs is undesirable due to the release of sequestered factors that leads to thrombosis [15]. TNF-α regulation of MMP-9 is of particular importance in atherosclerotic lesion development and in fibrous cap thinning [3,20]. Thus, up-regulation of MMP-9 expression by TNF-α can promote development of atherosclerotic lesions by multiple mechanisms that include stimulation of SMC proliferation and MMP-9 production.

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“…При цьому порушується цілісність ендотелію, вміст некротичного центру виходить у кров, а на місці утвореного дефекту починаються адгезія та агрегація тромбоцитів, що призводить до утворення тромбу, оклюзії коронарної судини і розвитку ГКС. У зоні інфаркту гинуть як кардіоміоци-ти, так і компоненти екстрацелюлярного матриксу (ЕЦМ), утвореного колагенами І, ІІІ, ІV типів, фібронектином, мірозином, глікозаміногліканами, еластинами [7]. Синтез колагену здійснюється фібробластами, що активуються за допомогою ангіотензину І і ІІ та тканинного фактора росту β (TФР-β), який, у свою чергу, секретується активованими макрофагами.…”

Section: вступunclassified

The role of matrix metalloproteinases and polymorphisms of their genes in the development of coronary heart disease

Погорєлова¹,

Гарбузова²,

Prystupa³

2018

Fiziol Zh

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У роботі систематизовано інформацію про роль матриксних метелопротеїназ (ММР), а саме ММР-3, -8, -9 ГКС -це ускладнення ІХС, основою яко-го є тромбоз коронарних артерій різного сту пеня, що формується над ділянкою роз-риву атеросклеротичної бляшки (АСБ) або пошкодження (ерозії) ендотелію [2]. В осно ві патогенезу цього мультифакторного захво-рювання лежить атеросклероз. Ініціюючу роль у розвитку останнього відіграє ушкодження ендотелію судин та його дисфункція. Внас-лідок виникнення ендотеліальної дис функ ції (ЕД) підвищується проникність ендотелію до ліпопротеїнів, збільшується його адгезивна здатність (посилюється синтез молекул адгезії: ІСАМ-1, ІСАМ-2, VСАМ-1), збільшується синтез прокоагулянтних факторів, цитокінів, факторів росту, вазоактивних речовин, а знижується ˗ антикоагулянтних факторів тощо. Надалі в інтимі артерій з'являються ліпідні плями і смужки в результаті накопичення в ОГЛЯДИ

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Atherosclerosis and proteinase activation

Cited by 225 publications

References 122 publications

Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese children

Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese children

Lysyl oxidase propeptide inhibits smooth muscle cell signaling and proliferation

The role of matrix metalloproteinases and polymorphisms of their genes in the development of coronary heart disease

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