A Role of Matrix Metalloproteinase-8 in Atherosclerosis

Laxton, Ross C.; Hu, Yanhua; Duchêne, Johan; Zhang, Feng; Zhang, Zhongyi; Leung, Kit‐Yi; Xiao, Qingzhong; Scotland, Ramona S.; Hodgkinson, Conrad P.; Smith, Katherine; Willeit, Johann; López-Otı́n, Carlos; Simpson, Iain; Kiechl, Stefan; Ahluwalia, Amrita; Xu, Qingbo; Ye, Shu

doi:10.1161/circresaha.109.200279

Cited by 117 publications

(138 citation statements)

References 52 publications

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“…By virtue of these processes, Lp-PLA 2 is involved in a positive-feedback loop of in ammation and atherosclerosis. MMP-8 and IL-6 are the key multifunctional cytokines which mediate in ammatory responses in atherosclerosis [32,33,34]. ese pro-in ammatory cytokines are known to contribute to vascular in ammation and plaque destabilization.…”

Section: Discussionmentioning

confidence: 99%

Amelioration of atherosclerosis in apolipoprotein E-deficient mice by inhibition of lipoprotein-associated phospholipase A2

Zhang

Zhang²,

Sun³

et al. 2013

CIM

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Purpose: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the pathogenesis of atherosclerosis, especially in advanced plaques. In the present study, the abilities of darapladib, a selective Lp-PLA2 inhibitor, and lentivirus-mediated Lp-PLA2 silencing on in ammation and atherosclerosis in apolipoprotein E-de cient mice were compared.Methods: Apolipoprotein E-de cient mice were fed on a high-fat diet and a constrictive collar was placed around the le carotid artery to induce plaque formation. e mice were randomly divided into control, negative control (NC), darapladib and RNA interference (RNAi) groups. Eight weeks a er surgery, lentivirus-mediated RNAi construct or darapladib were used to decrease the expression of Lp-PLA2. Plaques were collected ve weeks later for histological analysis. In ammatory gene expression in the atherosclerotic lesions were then determined at the mRNA and protein level.Results: e expression of pro-in ammatory cytokines was signi cantly reduced in the treatment group, compared to nontreatment group, whereas the plasma concentration of anti-in ammatory cytokines increased markedly. Moreover, our results demonstrated a signi cant reduction in plaque lipid content, as well as a rise in collagen content following Lp-PLA2 inhibition. Interestingly, when comparing the two methods of Lp-PLA2 inhibition, animals treated with Lp-PLA2 RNAi were found to exhibit lower plaque areas and enhanced improvement of plaque stability as compared with animals treated with darapladib. Darapladib had no attenuating e ect on atherosclerotic plaque area. ese therapeutic e ects were independent of plasma lipoprotein levels.Conclusions: Lp-PLA2 inhibition by darapladib or lentivirus-mediated RNAi ameliorated in ammation and atherosclerosis in apolipoprotein E-de cient mice. e e ect was more prominent in the RNAi group.

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Section: Discussionmentioning

confidence: 99%

Amelioration of atherosclerosis in apolipoprotein E-deficient mice by inhibition of lipoprotein-associated phospholipase A2

Zhang

Zhang²,

Sun³

et al. 2013

CIM

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“…apolipoprotein-E (ApoE) deficient mice develop atherosclerotic lesions similar to those observed in humans, although they do not spontaneously rupture or erode. Deficiency of MMP-8 in ApoE-null mice resulted in smaller lesions with increased collagen deposition (Laxton et al, 2009), and absence of MMP-13 (see below) led to thinner and less aligned collagen fibers in the plaque (Deguchi et al, 2005).…”

Section: Neoplastic Diseasesmentioning

confidence: 99%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

209

212

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a b s t r a c tHuman matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

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“…Сироватковий вміст ММР-8 асоційований із наявністю атеросклерозу [39,40], розвитком нес-табільності АСБ [41,42], ГКС [43] та із несприятливим серцево-судинним прогнозом [44]. Виявлено, що в ММР-8-нокаутованих мишей знижені вміст ангіотензину-ІІ, кон-центрація та експресія молекул адгезії судинного ендотелію 1 типу, кількість лейкоцитів у стінці судин, і нижчий рівень артеріального тиску [45]. Спостерігався сильний зв'язок вмісту ММР-8 і тканинного інгібітора ММР 1 типу (ТІМР-1) із таким фібриногену, СРБ, лейкоцитів у пацієнтів із ГКС [46].…”

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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A Role of Matrix Metalloproteinase-8 in Atherosclerosis

Cited by 117 publications

References 52 publications

Amelioration of atherosclerosis in apolipoprotein E-deficient mice by inhibition of lipoprotein-associated phospholipase A2

Amelioration of atherosclerosis in apolipoprotein E-deficient mice by inhibition of lipoprotein-associated phospholipase A2

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

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

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