Relationship of MMP-14 and TIMP-3 expression with macrophage activation and human atherosclerotic plaque vulnerability.

Matrix metalloproteinase-14 (MMP-14) promotes vulnerable plaque morphology in mice, whereas tissue inhibitor of metalloproteinases-3 (TIMP-3) overexpression is protective. MMP-14(hi) TIMP-3(lo) rabbit foam cells are more invasive and more prone to apoptosis than MMP-14(lo) TIMP-3(hi) cells. We investigated the implications of these findings for human atherosclerosis. In vitro generated macrophages and foam-cell macrophages, together with atherosclerotic plaques characterised as unstable or stable, were examined for expression of MMP-14, TIMP-3, and inflammatory markers. Proinflammatory stimuli increased MMP-14 and decreased TIMP-3 mRNA and protein expression in human macrophages. However, conversion to foam-cells with oxidized LDL increased MMP-14 and decreased TIMP-3 protein, independently of inflammatory mediators and partly through posttranscriptional mechanisms. Within atherosclerotic plaques, MMP-14 was prominent in foam-cells with either pro- or anti-inflammatory macrophage markers, whereas TIMP-3 was present in less foamy macrophages and colocalised with CD206. MMP-14 positive macrophages were more abundant whereas TIMP-3 positive macrophages were less abundant in plaques histologically designated as rupture prone. We conclude that foam-cells characterised by high MMP-14 and low TIMP-3 expression are prevalent in rupture-prone atherosclerotic plaques, independent of pro- or anti-inflammatory activation. Therefore reducing MMP-14 activity and increasing that of TIMP-3 could be valid therapeutic approaches to reduce plaque rupture and myocardial infarction.

Ventricular fibrillation induced by carotid sinus massage without preceding bradycardia.

Carotid sinus massage is widely used to detect carotid sinus hypersensitivity in patients presenting with syncope. Although generally safe, the risks associated with the procedure may not be fully appreciated by either the patient or the attending medical staff. We present the case of a patient who developed ventricular fibrillation during carotid sinus massage, not explained by preceding bradycardia or concomitant predisposing heart disease, and which highlights the need for ready availability of resuscitation equipment during this procedure.

Three-dimensional echocardiography is superior to multiplane transoesophageal echo in the assessment of regurgitant mitral valve morphology.

AIMS: Transoesophageal echocardiography (TOE) plays a vital role in the assessment of mitral valve morphology. However, the accuracy of TOE may be limited by inadequate recognition of all segments. We aimed to evaluate the role of three-dimensional (3D) echocardiography in this respect. METHODS AND RESULTS: Seventy-five patients were studied prior to mitral valve repair surgery. A scoring protocol was devised for recognition of the eight Carpentier segments (0=inadequate for analysis, 1=adequate, 2=good). Using surgical findings as the gold standard, TOE and 3D were compared for adequate recognition scores and accurate detection of functional morphology. Adequate recognition was more frequently obtained with 3D imaging (97% of segments by 3D c.f. 90% by TOE; p = 0.000). The major difference was seen at the commissures (adequate scores in 143/150 commissures by 3D c.f. 90/150 by TOE; p = 0.000). 3D matched more closely to surgical findings, achieving exact functional description in 92% of segments vs 79% segments with TOE (p = 0.000). This incremental value of 3D was seen in both commissures and the anterior leaflet but not in the posterior leaflet. CONCLUSIONS: In this study 3D was superior not only for complete recognition of the mitral valve but also for the accurate localisation and identification of pathology.

Beta-blockers are associated with lower C-reactive protein concentrations in patients with coronary artery disease.

PURPOSE: C-reactive protein is an important risk factor for coronary artery disease, and plasma concentrations are lowered by treatment with pravastatin and aspirin. We examined whether other cardiovascular drugs that are used in the treatment of ischemic heart disease affect C-reactive protein concentrations. SUBJECTS AND METHODS: Plasma C-reactive protein concentration was measured by high sensitivity immunonephelometric assay in 333 consecutive patients with stable angina and confirmed coronary artery disease who underwent diagnostic angiography. RESULTS: Patients prescribed beta-blockers had significantly lower mean C-reactive protein concentrations than did patients in whom these were not prescribed (by 1.2 mg/L, or 40% difference in geometric mean concentration; P <0.001). This association remained significant (P = 0.03) after excluding patients with contraindications to the use of beta-blockers, and adjusting for the probability of beta-blocker therapy (propensity score) and other clinical predictors of C-reactive protein concentration, including body mass index, high-density lipoprotein cholesterol level, family history of coronary artery disease, and angiographic severity. No differences among types or dosages of beta-blockers were evident. CONCLUSION: Beta-blockers may affect C-reactive protein concentrations. Randomized studies are required to confirm these findings.