Plaque Rupture is a Determinant of Vascular Events in Carotid Artery Atherosclerotic Disease: Involvement of Matrix Metalloproteinases 2 and 9

Abstract

Background and PurposeUnstable carotid atherosclerotic plaques are characterized by cap rupture, leading to thromboembolism and stroke. Matrix metalloproteinases (MMPs) have been implicated in the progression of atherosclerosis and plaque rupture. The aim of this study was to assess the relationship between the expressions of MMP-2 and MMP-9 and carotid plaque instability.MethodsEighty atherosclerotic plaques were collected from 74 patients undergoing carotid endarterectomy. Clinical information was obtained from each patient, and plaque morphology was examined at the macroscopic and microscopic levels. The immunohistochemical expressions of MMPs were graded using semiquantitative scales.ResultsMacroscopic ulceration (84.6% versus 63.4%, p=0.042) and microscopic cap rupture (79.5% versus 51.2%, p=0.010) were more common in symptomatic than in asymptomatic patients. Immunoreactivities of MMP-2 and MMP-9 were increased in 40 and 36 atheromatous plaques, respectively. Macroscopic ulceration was strongly correlated with the expressions of MMP-2 (p<0.001) and MMP-9 (p=0.001). There were significant correlations between increased MMP-2 expression and cap rupture (p=0.002), intraplaque hemorrhage (p=0.039), and a thin fibrous cap (p=0.002), and between increased MMP-9 expression and cap rupture (p=0.010) and a large lipid core (p=0.013).ConclusionsPlaque rupture was significantly associated with the development of vascular events in carotid atherosclerotic disease. MMP-2 and MMP-9 are strongly correlated with plaque instability.

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

“…MMP-2 expression strongly correlates with plaque rupture, by both degrading components of the fibrous cap and modulating the bioavailability of cytokines that contribute to plaque instability, as in the case of TNF-a (Heo et al, 2011;Kaneko et al, 2011).…”

Role of matrix metalloproteinase 9 and its tissue inhibitor 1 in development and prognosis of diabetic retinopathy

“…The study group (n=112) atherosclerosis as DM type 2 is an equivalent of coronary heart disease [23]. Furthermore, MMP-9 is considered as a marker of systemic inflammation and as a marker of atheromatous plaque destabilization [23].…”

Associations of Biomarkers of Atherosclerotic Plaques Instability (MMP-9, TIMP-1) and Zinc Levels in Carotid Atherosclerosis

“…Вместе с тем, склонные к разрыву АСБ сонной артерии являются независимыми факторами риска, наличия коронарного атеросклероза и развитие ИМ [1]. Уязвимость АСБ зависит от многих факторов таких, как дисфункция эндотелия, воспалительные клетки, продукция цитокинов, содержание гладкомышечной клетки и гибель клеток (апоптоз) [11].…”

“…Вместе с тем, склонные к разрыву АСБ сонной артерии являются независимыми факторами риска, наличия коронарного атеросклероза и развитие ИМ [1]. Уязвимость АСБ зависит от многих факторов таких, как дисфункция эндотелия, воспалительные клетки, продукция цитокинов, содержание гладкомышечной клетки и гибель клеток (апоптоз) [11].Ранимые АСБ имеет тонкую, воспаленную и бедным коллагеновым волокнам фиброзную покрышку, которые содержат повышенные уровни матриксных металлопротеиназ (ММП) [14]. Существует дисбаланс между ММП и тканевыми ингибиторами (ТИМП) в нестабильных АСБ сонных артерий, что определяет уровни этих маркеров в плазме крови [16].…”