Differences in Matrix Metalloproteinase-1 and Matrix Metalloproteinase-12 Transcript Levels Among Carotid Atherosclerotic Plaques With Different Histopathological Characteristics

Abstract

Background and Purpose-Previous studies have shown that atherosclerotic lesions express a number of matrix metalloproteinases (MMPs). Here we investigated whether transcript levels of MMP-1, -3, -7, -9, and -12 in carotid atherosclerotic plaques were correlated with histological features and clinical manifestations. Methods-Atherosclerotic plaques (nϭ50) removed from patients undergoing carotid endarterectomy were classified histologically using a system proposed by Virmani et al, and MMP-1, -3, -7, -9, and -12 transcript levels in these tissues were quantified by real-time reverse-transcriptase polymerase chain reaction. Results-Compared to plaques with a thick fibrous cap, those with a thin cap had a 7.8-fold higher MMP-1 transcript level (Pϭ0.006). MMP-3, -7, and -12 were 1.5-fold, 1.8-fold, and 2.1-fold, respectively, higher in thin cap plaques, but the differences did not reach statistical significance. MMP-12 transcript levels were significantly increased in ruptured plaques compared with lesions without cap disruption (Pϭ0.001). MMP-9 transcript levels were similar among the different types of lesion. MMP-1 and -12 transcript levels were significantly higher in plaques from patients with amaurosis fugax, than in those from asymptomatic patients (Pϭ0.029 and Pϭ0.008 for MMP-1 and MMP-12, respectively), than in those from patients with stroke (Pϭ0.027 and Pϭ0.001, respectively), and than in those from patients with transient ischemic attack (Pϭ0.046 and Pϭ0.008, respectively). Conclusions-These data support a role of MMP-1 and -12 in determining atherosclerotic plaque stability.

Elevated Plasma Levels of MMP-12 Are Associated With Atherosclerotic Burden and Symptomatic Cardiovascular Disease in Subjects With Type 2 Diabetes

“…16 It localizes selectively to macrophages surrounding the lipid core 17 and is associated with decreased fibrous cap thickness, plaque rupture, and an increased risk of adverse cardiovascular events after endarterectomy. 18,19 Importantly, using a genome-wide age-at-onset informed approach, Traylor and …”

Protease-Activated Receptors in Cardiovascular Diseases

“…4 Atherosclerotic plaques also contain inflammatory cells such as macrophages that express and secrete cytokines. In addition, macrophages produce matrix metalloproteases (MMPs) in vulnerable plaques, 55,56 including the recently identified PAR1 agonist MMP-1. 15 Plaques that had been assessed as unstable because of a thin fibrous cap demonstrated 8-fold higher MMP-1 levels than lesions that harbor a thicker, more stable cap structure.…”

“…15 Plaques that had been assessed as unstable because of a thin fibrous cap demonstrated 8-fold higher MMP-1 levels than lesions that harbor a thicker, more stable cap structure. 56 Therefore, targeting PAR1 downstream of MMP-1 may be efficacious in the control or reduction of plaque rupture in atherosclerotic disease. Cardiomyocytes also contain functional PAR1 and PAR2.…”

Patients with vulnerable coronary plaques have higher serum metalloproteinase-1 levels

“…También se ha descrito una fuerte correlación entre el porcentaje de núcleo lipídico ocupado por hemorragia y el porcentaje del perímetro del núcleo lipídico positivo para MMP-1 9 . Morgan y col demostraron mayor expresión genética de MMP-1 en placas con cáp-sula fina 30 . Guo y col describieron mayor concentración de MMP-1 en el tejido de placas rotas frente a las no rotas 10 .…”