Local catheter-based delivery of antithrombotic or antiproliferative drugs: a new concept for prevention of restenosis.

Background: Drug eluting stents have reduced the incidence of restenosis after percutaneous coronary interventions significantly, but cause concern about long term safety. Local drug delivery using special application catheters is an alternative approach for intracoronary pharmacotherapy. Besides the fact, that no problematic coating as drug carrier has to be used, a local delivery independent of the stent itself by using catheter techniques offers further advantages - such as the possibility to treat the whole vessel wall, stent edges and adjacent vessel segments and not only the area close to the stent struts.

Platelet GPVI binds to collagenous structures in the core region of human atheromatous plaque and is critical for atheroprogression in vivo.

Platelet adhesion to the atherosclerotic vascular wall induces thrombosis and boosters vascular inflammation and atheroprogression. In the present study we studied the binding of the platelet collagen receptor glycoprotein (GP) VI to human atherosclerotic plaques (AP) and the role of GPVI-mediated platelet adhesion for atheroprogression. Soluble GPVI-Fc fusion protein bound to immobilized collagen type I, collagen type III, and predominantly to the core region of human carotid atheromatous plaques.

Catheter-based local antiproliferative therapy in kissing balloon technique for in-stent stenosis of coronary artery bifurcation lesions.

There is currently no promising interventional solution for in-stent stenosis in previously stented bifurcation lesions, even with drug-eluting stents. Rather than being restricted to stent struts, catheter-based local antiproliferative therapy offers the advantage of homogenous drug transfer to the whole vessel wall, and thereby allows for intracoronary pharmacotherapy without adding additional layers of metal into an already stented lesion. The newly developed GENIE catheter (Acrostak Corp, Switzerland), applied in the kissing balloon technique, allows for delivery of liquid paclitaxel into whole bifurcation lesions without repeat stent implantation.

Platelets in regenerative medicine.

Stem and progenitor cells have evolved as the central cell type in regenerative medicine. This focussed approach may, however, sometimes narrow the point of view. Recently, platelets have been shown to strongly influence progenitor cell biology and to serve as regenerative cells themselves.

Individualized antithrombotic therapy in high risk patients after coronary stenting. A double-edged sword between thrombosis and bleeding.

Dual antiplatelet therapy with aspirin and clopidogrel is currently the standard therapy after coronary stent implantation to prevent a life-threatening stent thrombosis. However, a variety of procedural and individual factors contribute to the individual patient risk and have to be taken into account to allow for an individual recommendation for both the duration and intensity of the antiplatelet therapy. Obviously, the benefit of the prevention of stent thrombosis by antithrombotic therapy has to outweigh the risk of severe bleeding complications.

Platelet-vessel wall interactions in atherosclerotic disease.

During the prolonged course of atherosclerotic disease, platelets are of central importance as they contribute to the initiation of the disease, to its progression and acute exacerbation but also provide potential regenerative mechanisms. Platelets secrete chemokines and cytokines that mediate vascular inflammation and are in turn activated by substances released from cells of the vascular wall. These interactions represent positive and negative feedback loops, which in case of dysregulation may lead to development and progression of disease.

Platelet interaction with progenitor cells: vascular regeneration or inquiry?

Increasing evidence supports the role of stem and progenitor cells in vascular regeneration or injury. Following tissue ischemia, progenitor cells are mobilized from their bone marrow or peripheral niches into circulation, adhere at sites of vascular lesion and differentiate into a variety of mature cell types according to their origin and the local environment. Impairment in this pathophysiological process due to either low numbers of circulating progenitor cells or dysfunctional progenitor cells leads to inadequate vascular repair and upon co-existence with different cardiovascular risk factors to vascular injury and atherosclerosis.

Platelet lipoprotein interplay: trigger of foam cell formation and driver of atherosclerosis.

In the last decade, it was recognized that platelets and lipoproteins play a pivotal role in both early and late atherogenesis. Beside cellular interactions of platelets with other blood cells and vascular cells, interactions with lipoproteins seem to be quite important. Lipoproteins are fundamental 'players' in atherogenesis since they change the properties of different cells involved in atherosclerosis and thrombosis.

Platelets: inflammatory firebugs of vascular walls.

Atherosclerosis is an inflammatory disease. Platelets can "inflame" the vascular wall by various mechanisms and thereby initiate and support the development of atherosclerosis. Platelet interaction with leukocytes, endothelial cells, and circulating progenitor cells triggers autocrine and paracrine activation processes, leading to inflammatory and atherogenic cascades at the vascular wall.

Platelet-derived stromal cell-derived factor-1 regulates adhesion and promotes differentiation of human CD34+ cells to endothelial progenitor cells.

Background: Peripheral homing of progenitor cells in areas of diseased organs is critical for tissue regeneration. The chemokine stromal cell-derived factor-1 (SDF-1) regulates homing of CD34+ stem cells. We evaluated the role of platelet-derived SDF-1 in adhesion and differentiation of human CD34+ cells into endothelial progenitor cells.

Extracellular matrix metalloproteinase inducer (CD147) is a novel receptor on platelets, activates platelets, and augments nuclear factor kappaB-dependent inflammation in monocytes.

In atherosclerosis, circulating platelets interact with endothelial cells and monocytes, leading to cell activation and enhanced recruitment of leukocytes into the vascular wall. The invasion of monocytes is accompanied by overexpression of matrix metalloproteinases (MMPs), which are thought to promote atherosclerosis and trigger plaque rupture. Following interaction with itself, the extracellular matrix metalloproteinase inducer (EMMPRIN) induces MMP synthesis via a little-known intracellular pathway.

Impaired platelet function reduces myocardial infarct size in Galphaq knock-out mice in vivo.

Platelet aggregation and secretion play a crucial role in acute coronary syndromes. In Galpha(q) knock-out mice (Galpha(q)(-/-)) platelet function is eliminated in terms of aggregation and secretion of cytokines. We investigated whether restricted platelet aggregation and secretion reduces myocardial infarct size in vivo.

Platelet interaction with progenitor cells: potential implications for regenerative medicine.

Circulating endothelial progenitor cells have been shown to instigate new vessel formation via angiogenesis and neovascularisation and to induce ongoing vascular and tissue repair by domiciliation to sites of vascular or tissue damage. However, the mechanisms that recruit circulating endothelial progenitor cells towards vascular lesions and regulate repair mechanisms of ischemic peripheral organs are poorly described. Domiciliation of endothelial progenitor cells in peripheral tissue is a multi-step cascade including initial adhesion to subendothelial matrix or endothelium, transmigration and invasion of the target tissue.

Platelet-associated LIGHT (TNFSF14) mediates adhesion of platelets to human vascular endothelium.

LIGHT (TNFSF 14) belongs to the tumor necrosis factor super-family and is expressed by different types of immune cells. Recently, LIGHT was found to be associated with platelets and released upon activation. Activation of endothelial cells by recombinant LIGHT results in pro-inflammatory and pro-thrombotic changes, qualitatively comparable to effects of CD40 ligand.

Molecular pathways used by platelets to initiate and accelerate atherogenesis.

Purpose Of Review: The response to injury model in the development of atherosclerosis is broadly accepted by the scientific audience. Platelets are generally not believed to be involved in the initiation of atherosclerosis. New data imply, however, that the response to injury model is too simple for a complete understanding of the inflammatory disease atherosclerosis.

Association of platelet-derived soluble glycoprotein VI in plasma with Alzheimer's disease.

Accumulating evidence from epidemiological, clinical and experimental studies suggests that vascular risk factors and angiopathic mechanisms are involved in the pathogenesis of Alzheimer's disease (AD). Platelets could be the missing link between AD and the vasculature. Soluble glycoprotein VI (sGPVI) and beta-thromboglobulin (beta-TG) plasma and cerebrospinal fluid (CSF) levels as markers of platelet activity were measured in 30 AD patients and 20 age-matched healthy elderly controls by ELISA.

Challenges in the treatment of patients with essential thrombocythemia and acute coronary syndrome.

Essential thrombocythemia (ET) is an acquired clonal hematological stem-cell disorder that is characterized by a persistent increase in platelet count over 600,000/microl and elevated megakaryocyte levels in the bone marrow. Patients with ET are on the one hand at risk of thrombosis and on the other hand of hemorrhagic events especially in patients with very high platelet accounts. We report two illustrative cases with ET and acute coronary syndrome from our recent clinical experience illustrating the challenges in the antithrombotic treatment of these patients.

Chemokine fractalkine mediates leukocyte recruitment to inflammatory endothelial cells in flowing whole blood: a critical role for P-selectin expressed on activated platelets.

Background: The membrane-bound chemokine fractalkine (CX3CL1) is expressed on various cell types such as activated endothelial cells and has been implicated in the inflammatory process of atherosclerosis. The aim of the present study was to dissect the role of fractalkine in leukocyte recruitment to inflamed endothelium under arterial shear forces.

Methods And Results: With the use of immunofluorescence and laminar flow assays, the present study shows that human umbilical vein endothelial cells stimulated with tumor necrosis factor-alpha and interferon-gamma abundantly express CX3CL1 and promote substantial leukocyte accumulation under arterial flow conditions.

Hyperresponsiveness of platelets in ischemic stroke.

Platelet activation and aggregation are critical in the pathogenesis of acute ischemic cerebrovascular diseases. The aim of our study was to characterize platelet function in patients with acute ischemic stroke or transient ischemic attack (TIA), and to evaluate the effect of platelet activation on clinical outcome. One hundred thirty-eight consecutive patients with TIA (n = 74) or stroke (n = 64) were enrolled in this study.

Adenosine stress first pass perfusion for the detection of coronary artery disease in patients with aortic stenosis: a feasibility study.

Detection of coronary artery disease (CAD) with magnetic resonance imaging (MRI) using adenosine stress first pass perfusion in patients with aortic stenosis in comparison with invasive angiography. Twenty-three consecutive patients (15 male, mean age 68 +/- 12 years) with relevant aortic stenosis (aortic valve area 0.90 +/- 0.

Magnetic resonance imaging to assess acute changes in atrial and ventricular parameters after transcatheter closure of atrial septal defects.

Purpose: To evaluate acute changes in atrial and ventricular parameters by the use of cardiac magnetic resonance imaging (MRI) in patients with percutaneous transcatheter atrial septal defects (ASD) closure.

Materials And Methods: The study included 14 patients (six males and eight females, 45 +/- 18 years) with congenital ASD. Cardiac MRI (1.

Human herpesvirus 6 subtype A-associated myocarditis with 'apical ballooning'.

A 67-year-old woman who presented with acute chest pain is reported. Three days before admission, she suffered from a flu-like infection. Coronary angiography showed no coronary stenosis.