http://repub.eur.nl/res/aut/36685/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/33633/ 2011-09-01T00:00:00Z Aims Atherosclerotic plaque rupture and subsequent thrombus formation are the major cause of acute cardiovascular events. Local plaque markers may facilitate detection of the vulnerable plaque and help identify the patient at risk for cardiovascular events. Matrix metalloproteinases (MMPs) are prevalent in the arterial wall throughout the arterial system and are associated with local plaque destabilization. We hypothesized that local MMP plaque levels are predictive for atherosclerotic cardiovascular events in other vascular territories. Methods and resultsAtherosclerotic plaques were obtained from 543 patients undergoing carotid endarterectomy (CEA). Plaques were analysed for the presence of macrophages, lipid-core, smooth muscle cells, collagen, calcification, and presence of plaque haemorrhage. MMP-2, MMP-8, and MMP-9 levels were assessed within the plaque. Following CEA, all patients underwent follow-up during 3 years. The primary outcome was defined as the composite of vascular death, non-fatal vascular event, and surgical or percutaneous vascular intervention. In contrast with MMP-2 plaque levels, MMP-8 and MMP-9 levels in the plaque were associated with an unstable carotid plaque composition and clinical presentation at baseline. Increased plaque MMP-8 level (>4.58) was associated with an increased risk for the occurrence of secondary manifestations of atherosclerotic disease during follow-up [hazard ratio 1.76, 95 CI (1.252.48)] (P 0.001), whereas plaque MMP-2 and MMP-9 levels were not predictive for systemic cardiovascular events. ConclusionIn contrast with MMP-2, increased carotid MMP-8 and MMP-9 plaque levels are associated with an unstable plaque phenotype. High collagenase MMP-8 levels in the carotid plaque are associated with the occurrence of systemic cardiovascular outcome during follow-up. http://repub.eur.nl/res/pub/26681/ 2011-07-01T00:00:00Z Plaque rupture and subsequent thrombotic occlusion of the coronary arteryaccount for as many as three quarters of myocardial infarctions. Theconcept of plaque stabilisation emerged about 20 years ago to explainthe discrepancy between the reduction of cardiovascular events in patientsreceiving lipid lowering therapy and the small decrease seen in angiographicevaluation of atherosclerosis. Since then, the concept of a vulnerableplaque has received a lot of attention in basic and clinical researchleading to a better understanding of the pathophysiology of thevulnerable plaque and acute coronary syndromes. From pathological andclinical observations, plaques that have recently ruptured have thin fibrouscaps, large lipid cores, exhibit outward remodelling and invasion byvasa vasorum. Ruptured plaques are also focally inflamed and this maybe a common denominator of the other pathological features. Plaqueswith similar characteristics, but which have not yet ruptured, are believ ed to be vulnerable to rupture. Experimental studies strongly support thevalidity of anti-inflammatory approaches to promote plaque stability. Unfortunately,reliable non-invasive methods for imaging and detection ofsuch plaques are not yet readily available. There is a strong biologicalbasis and supportive clinical evidence that low-density lipoprotein loweringwith statins is useful for the stabilisation of vulnerable plaques. Thereis also some clinical evidence for the usefulness of antiplatelet agents,beta blockers and renin-angiotensin-aldosterone system inhibitors forplaque stabilisation. Determining the causes of plaque rupture and designingdiagnostics and interventions to prevent them are urgent prioritiesfor current basic and clinical research in cardiovascular area.