Plasma Matrix Metalloproteinase-8 Concentrations are Associated With the Presence and Severity of Coronary Artery Disease

Abstract

nterstitial collagen, especially type I, is a major component of atherosclerotic plaques 1-3 and although collagen synthesis is generally upregulated in atherosclerotic plaques, 3 it is the balance between collagen synthesis and breakdown that is important for plaque growth, plaque vulnerability, and vascular remodeling. [4][5][6] The matrix metalloproteinases (MMP) 1, 8 and 13 initiate the collagen breakdown 7 and MMP-8 in particular degrades type I collagen preferentially and more potently than MMP-1 or 9 However, MMP-8, known as neutrophil collagenase, was previously thought to be produced only by neutrophils, which are not commonly present in plaques, but recently, it has been found that endothelial cells, smooth muscle cells, and macrophages in atherosclerotic plaques express and produce Therefore, the present study aimed to elucidate whether or not plasma MMP-8 concentrations are associated with the presence and severity of coronary artery disease (CAD). Circulation Journal Vol.69, September 2005 Methods Study PatientsWe measured the plasma MMP-8 concentration in 250 consecutive patients (mean age 65±8 years, range 40-80) who underwent elective coronary angiography for suspected CAD at the National Defense Medical College Hospital. Patients with myocardial infarction within the past 6 months, those with unstable angina at rest within the past 48 h, or those with a history of percutaneous coronary intervention or coronary artery bypass surgery were excluded, as were those with heart failure, cardiomyopathy or valvular heart disease.Hypertension was defined as blood pressure ≥140/90 mmHg or on relevant medication (122 (49%) patients); hyperlipidemia was defined as total cholesterol >240 mg/dl or relevant medication (65 (26%) patients taking statins); diabetes mellitus was defined as fasting plasma glucose ≥126 mg/dl or on insulin or hypoglycemic drugs.Our study was approved by the institutional Ethics Committee. After giving written informed consent, each patient had a fasting blood sample taken on the morning of the day that angiography was performed. Plasma MMP-8 MeasurementBlood samples were collected in EDTA-containing tubes and the plasma was stored at -80°C. Plasma MMP-8 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) using a commercially available kit (MMP-8 Human Biotrak ELISA System, Amersham

The balance of serum matrix metalloproteinase-8 and its tissue inhibitor in acute coronary syndrome and its recurrence

“…In publications earlier, high circulating MMP-8 levels have been related to the presence and severity of coronary artery disease [25], carotid artery plaque progression [13], and subclinical atherosclerosis [16], whereas the concentrations have been reported to be decreased in patients with heart failure [26] or cerebral ischemia [27]. In our previous prospective study with a follow-up time of 10 years, serum MMP-8 concentrations associated with AMI as well as death from coronary heart disease, CVD, or from any cause in men free of CVD at baseline.…”

Evaluation of plasmatic MMP-8, MMP-9, TIMP-1 and MPO levels in obese and lean women

“…Although little is known about the biological effects of MMP-8, some studies have shown elevated levels of MMP-8 in subclinical and clinical atherosclerosis [13], unstable angina [22], metabolic syndrome [12], and childhood obesity [23]. Conversely, reduced levels of MMP-8 were associated with diastolic heart failure [24].…”

“…In addition, clinical studies have shown that alteration in the expression or activity of MMPs and/or TIMPs is an important mechanism underlying the pathophysiology of some cardiovascular diseases [5][6][7][8] and contributes to ventricular dysfunction [6] and atherosclerotic lesions [9]. Studies evaluating circulating levels of MMP-8 (neutrophil collagenase) in obese women without associated comorbidities have not yet been evaluated, although some studies have shown higher MMP-8 levels in subjects presenting with cardiovascular disorders [12][13][14][15].…”

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

“…У дослідженнях in vitro [38] було пока-зано, що ендотеліальні клітини, макрофаги, ГМК у ділянці атеросклеротичних уражень експресують ММР-8 після стимулювання прозапальними цитокінами: IL-1β, ФНП-α, CD40, її експресія зростає в разі швидкого прогресування ушкодження. 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].…”

“…Опубліковано праці, присвячені вив-ченню комплексу ММР-9/ТІМР-1 при ІХС, які свідчать, що зростання їх співвідно-шення відбувається у хворих на нестабіль-ну стенокардію та при збільшенні класу стабільної стенокардії [39,41,48], а змен-шення ˗ у хворих на гіпертонічну хворобу, що свідчить про ремоделювання лівого шлуноч-ка (його ексцентричну або концентричну гіпертрофію). Збільшення вмісту ТІМР-1 асоціюється з несприятливими типами ремоделювання лівого шлуночка, а значення більше за 1 200 нг/мл є предиктором розвитку ХСН [49].…”