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Matrix metalloproteinases (MMPs) of atherosclerotic tissue contribute to plaque rupture triggering acute coronary syndromes (ACS). Several MMPs, including MMP-2, are also contained in platelets and released upon activation. An increase in circulating levels of MMP-2 has been reported in patients undergoing percutaneous coronary interventions (PCI), but its time-course and origin remain unclear. Aims of our study were to assess the time-course of MMP-2 release in blood of stable and unstable coronary artery disease patients undergoing PCI and to unravel the possible contribution of platelets to its release.Peripheral blood samples were drawn immediately before, 4 and 24 h after PCI from patients with ACS (NSTEMI or STEMI, n = 21) or with stable angina (SA, n = 21). Platelet-poor plasma and washed platelet lysates were prepared and stored for subsequent assay of MMP-2 and β-thromboglobulin (β-TG), a platelet-specific protein released upon activation.Plasma MMP-2 and β-TG increased significantly 4 h after PCI and returned to baseline at 24 h in ACS patients, while they did not change in SA patients. Platelet content of MMP-2 and β-TG decreased significantly 4 h after PCI in patients with ACS, compatible with intravascular platelet activation and release, while they did not change in patients with SA.PCI triggers the release of MMP-2 in the circulation of ACS patients but not in that of patients with SA. Platelets activated by PCI contribute to the increase of plasma MMP-2 releasing their MMP-2 content. Given that previous mechanicistic studies have shown that MMP-2 may sustain platelet activation and unstabilize downstream-located plaques and in the long term favour restenosis and atherosclerosis progression, these data may encourage the search for therapeutic agents blocking MMP-2 release or activity in ACS.

Introduction The use of topical NSAIDs is frequent in ophthalmology to reduce the local inflammatory reaction resulting from surgical procedures. Ocular use of some drugs was previously found to lead to significant systemic absorption with possible systemic effects. NSAIDs may enhance the hemorrhagic risk of anticoagulant and antiplatelet drugs. Aim of our study was to evaluate the systemic effects of two NSAIDs given by eyedrops on platelet COX-1 and on ex vivo and in vivo platelet activation. Materials and methods 20 patients planned to undergo cataract surgery were randomized to the use of an ophthalmic solution containing Diclofenac or Indomethacin. Blood was taken at enrollment (baseline) and after 3 days of therapy (1 drop, 4 times a day). Arachidonic Acid (AA)-induced light transmission aggregometry (LTA), PFA-100® C-EPI, circulating platelet P-Selectin expression by flow cytometry and serum and AA-induced TxB2 production were evaluated before and after eyedrop therapy. Results AA (0.1–0.2 mM)-induced LTA was significantly reduced after ocular indomethacin but not after diclofenac. PFA-100® C-EPI closure time was also significantly prolonged in the indomethacin group but not in the diclofenac group. Circulating platelet P-selectin expression was significantly reduced after treatment with indomethacin compared with diclofenac. Finally, treatment with eyedrop indomethacin, but not with diclofenac, strikingly suppressed AA-induced TxB2 generation, while treatment with diclofenac did not modify it. Conclusions Our data show that indomethacin administered by ophthalmic eye drops has a relevant systemic antiplatelet effect. This should be taken into account in patients under concurrent therapy with antiplatelet or anticoagulant agents.

The HIV epidemic has huge dimensions: in 2009, 33.3million people worldwide, including 2.5million children, were affected by human immunodeficiency virus (HIV) infection. The introduction of Highly Active Anti-Retroviral Therapy (HAART) has significantly modified the course of HIV disease, with longer survival and improved quality of life, but it has simultaneously lead to the appearance of previously unrecognized complications, such as ischemic cardiovascular events. Many studies have shown a higher rate of premature atherosclerosis in patients with HIV infection, leading to coronary, cerebrovascular, or peripheral arterial disease. However, it is still debated whether cardiovascular complications are a consequence of HIV infection itself or of the long-term use of HAART. In particular, myocardial infarction has been suggested to be associated with the use of abacavir. Endothelial dysfunction and platelet activation are markers of atherosclerosis and of increased cardiovascular risk. Here we review the evidence that endothelial dysfunction and platelet alterations are associated with chronic HIV infection, the possible role of different HAARTs, and the possible pathophysiologic mechanisms. Potential therapeutic implications are also discussed.

Among the so called antiphospholipid (aPL) antibodies Lupus Anticoagulant (LAC) is considered the strongest risk factor for thromboembolic events. In individuals without a previous thromboembolic event (carriers), LAC is a risk factor when associated with the presence of anticardiolipin (aCL) and aβ2-Glycoprotein I (aβ2GPI) antibodies. On the other hand, data on carriers of isolated LAC positivity are sparse and inconclusive. The aim of this study was to prospectively determine the incidence of thrombosis in a cohort of carriers of isolated LAC positivity. One-hundred seventy-nine carriers of LAC confirmed twelve weeks apart and in a reference laboratory were studied. During a total follow up of 552 person-years, there were seven thromboembolic events (1.3% person-y). All the seven patients had at least one adjunctive major risk factor for thrombosis. The cumulative incidence of thromboembolic events was 3.1% (95% CI 0.6-5.6) after 2years, and 5.9% (95% CI 1.2-10.6) after 5 and 10years. On a multivariate regression analysis considering age, sex, autoimmune disease, risk factors for arterial and venous thrombosis, use of aspirin, only age was found to be an independent predictor of thromboembolic events (HR=1.1, 95% CI 1.0-1.2, p=0.02). These data might be relevant in clinical practice and underline the importance of differentiating LAC carriers in terms of isolated positivity or positivity associated with the presence of antibodies to aCL and β2-glycoprotein I.

A cause-effect relation between the synthesis and release of prostaglandins and fibrinolytic activation has been suggested. We have reinvestigated this relation in a double-blind, placebo-controlled, cross-over study with cyclooxygenase inhibitors (aspirin and indomethacin) and a thromboxane synthase inhibitor (dazoxiben) in nine healthy volunteers. Euglobulin fibrinolytic activity (EFA) and tissue-type plasminogen activator antigen level (t-PA:Ag) were studied before and after 10 min of venous occlusion. Despite effective suppression of prostaglandin synthesis by aspirin and indomethacin and enhanced prostacyclin formation by dazoxiben, baseline EFA and t-PA:Ag levels did not significantly change within 2 hours after ingestion of the different drugs. The release of t-PA by venous occlusion was not altered by any of the drugs. Thus, our study does not support the hypothesis that prostaglandins play a significant role in the modulation of the synthesis or release of t-PA.

In the last few years* the interest in the metabolism of choline glycerophospholipids (ChoGpl) in platelets has increased since they represent about 40% of total membrane phospholipids (1) and participate to the release of arachidonic acid after stimulation (21. As in other tissues they consist mainly of i ,2-diacyl-a-glycero-3-phosphochocholine (diacyl-GroPCho) which accounts for about *O% of the lipid class. Choline plasmalogens (ChoPlas) and 1-0-alkyl-2-acyl-a-glycero-3phosphocholine (alkylacyl-GroPChol are also present in platelet membranes and each of them represents around 10% of total ChoGpl (1). Alkylacyl-GroPCho is believed to be the metabolic precursor of alkylacetyl-GroPCho (PAF-acether) (3). The role of choline plasmalogens is not known but recently some evidence has been reported on their contribution in arachidonic acid release during the first minute after stimulation of human platelets with thrombin (41. The synthesis of ChoGpl in platelets has been studied using different labeled precursors and it has been demonstrated that they can be synthesized de nave (5-7) or by methylation of ethanolamineglycerophospholipids (EtnGpl) (8-141. For both pathways, the incorporation of the precursors into ChoPlas has never been considered, since these data refer to the total class of ChoGpl or to diacyl-type only (5-141. The pathway for the synthesis of ChoPlaa in mammalian tissues is still largely unknown, since alkylacyl-GroPCho cannot be desaturated to the corresponding alKeny1. derivatives (15)~ as reported far the biosynthesis of ethanolamine plasmalogens (EtnPlas ) (16).