These data indicate that CRP exerts direct effects on ECs and SMCs by promoting proliferation and TF expression and support the notion that CRP, besides representing a marker of inflammation, is an effector molecule able to induce a pro-atherothrombotic phenotype in cells of the vessel wall.

Background-␤-Blockers improve clinical outcome when administered early after acute myocardial infarction. However, whether ␤-blockers actually reduce the myocardial infarction size is still in dispute. Cardiac magnetic resonance imaging can accurately depict the left ventricular (LV) ischemic myocardium at risk (T2-weighted hyperintense region) early after myocardial infarction, as well as the extent of necrosis (delayed gadolinium enhancement). The aim of this study was to determine whether early administration of metoprolol could increase myocardial salvage, measured as the difference between the extent of myocardium at risk and myocardial necrosis. Methods and Results-Twelve Yorkshire pigs underwent a 90-minute left anterior descending coronary occlusion, followed by reperfusion. They were randomized to metoprolol (7.5 mg during myocardial infarction) or placebo. Global and regional LV function, extent of myocardium at risk, and myocardial necrosis were quantified by cardiac magnetic resonance imaging studies performed 4 and 22 days after reperfusion in 10 survivors. Despite similar extent of myocardium at risk in metoprolol-and placebo-treated pigs (30.9% of LV versus 30.6%; PϭNS), metoprolol resulted in 5-fold-larger salvaged myocardium (32.4% versus 6.2% of myocardium at risk; Pϭ0.015). The LV ejection fraction significantly improved in metoprolol-treated pigs between days 4 and 22 (37.2% versus 43.0%; Pϭ0.037), whereas it remained unchanged in pigs treated with placebo (35.1% versus 35.0%; PϭNS). The extent of myocardial salvage was related directly to LV ejection fraction improvement (Pϭ0.031) and regional LV wall motion recovery (Pϭ0.039) at day 22. Conclusions-Early metoprolol administration during acute coronary occlusion increases myocardial salvage. The extent of myocardial salvage, measured as the difference between myocardium at risk and myocardial necrosis, was associated with regional and global LV motion improvement. (Circulation. 2007;115:2909-2916.)

Background-Recent studies indicate that T-cell activation may play an important role in the pathophysiology of acute coronary syndromes (ACS). However, although those studies detected T-cell expansion in peripheral blood cells, demonstration of specific T-cell expansion within the plaque of patients with ACS is lacking. The present study aims to address whether a specific, immune-driven T-lymphocyte recruitment occurs within the unstable plaque of patients with ACS. Methods and Results-We simultaneously examined the T-cell repertoire using CDR3 size analysis both in coronary plaques (obtained by directional atherectomy) and in peripheral blood of patients with either ACS (nϭ11) or chronic stable angina (nϭ10). Unstable plaques showed a 10-fold increase in T-cell content by quantitative PCR. Using spectratyping analysis, we found several specific T-cell clonotype expansions only in unstable plaque from each patient with ACS, indicating a specific, antigen-driven recruitment of T cells within unstable lesions. Conclusions-For the first time, T-cell repertoire was investigated directly into coronary plaques; using this approach, we demonstrate that coronary plaque instability in the setting of ACS is associated with immune-driven T-cell recruitment, specifically within the plaque.

The main function of platelets is to participate in primary hemostasis through four distinct steps: adhesion, activation, secretion, and aggregation. Unraveling the molecular mechanisms underlying these steps has led to a better understanding of the pathophysiology of bleeding disorders, on one hand, and of thrombotic diseases, such as acute coronary syndromes, on the other. Platelets are cytoplasmic fragments of megakaryocytes formed in the bone marrow. They lack nuclei but contain organelles and structures, such as mitochondria, microtubules, and granules. Platelet granules contain different bioactive chemical mediators, many of which have a fundamental role in hemostasis and/or tissue healing. The platelet cytoplasm contains an open canalicular system that increases the effective surface area for the intake of stimulatory agonists and the release of effector substances. The submembrane region contains microfilaments of actin and myosin that mediate morphologic alterations characteristic of shape change. Resting platelets remain in the circulation for an average of approximately 10 days before being removed by macrophages of the reticuloendothelial system. A wide variety of transmembrane receptors cover the platelet membrane, including many integrins, leucine-rich repeat receptors, G protein-coupled receptors, proteins belonging to the immunoglobulin superfamily, C-type lectin receptors, tyrosine kinase receptors, and a variety of other types. In this article, we will review platelet biology under physiological and pathological conditions, with particular emphasis on the function of their membrane receptors.