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. Platelets are the first circulating blood cells that interact with the injured vessel wall. They contain a number of growth factors, chemokines, cytokines and adhesive proteins that are released or surface-expressed upon platelet activation including adhesion. Recent studies suggest that platelet interaction with endothelial progenitor cells influences chemotaxis, adhesion, activation and differentiation of progenitor cells. Release of the chemokine SDF-1 from platelets enhances neovascularization through mobilization of progenitor cells. Adherent platelets recruit bone marrow-derived progenitor cells to arterial thrombi in vitro and in vivo and induce their subsequent differentiation towards an endothelial phenotype. Moreover, platelet accumulation in a co-culture system with CD34(+) progenitor cells results in the differentiation of the latter to macrophages in vitro. Although further studies are needed to elucidate the mechanisms that platelets determine the fate of endothelial progenitor cells into vascular lesions, platelet interaction with progenitor cells seems to play a decisive role in vascular and tissue regeneration.     

Acute coronary syndromes, response to clopidogrel, and worsened cardiovascular outcomes: the hen and the egg dilemma: reply

We thank Dr Serebruany for his interest and careful readingof our article entitled "Low response to clopidogrel is associatedwith cardiovascular outcome after coronary stent implantation". He critically remarked the influence of acute coronary syndromes(ACS) on response to clopidogrel in our patient cohort. We agreewith Dr Serebruany that acute coronary events may have substantialinfluence on measured platelet activity and, of     

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. Ventriculography showed moderately reduced left ventricular function characterized by the so-called 'apical ballooning'. Endomyocardial biopsies and polymerase chain reaction analysis of the plasma revealed an acute infection with human herpesvirus 6 subtype A. Histological and immunohistochemical analyses revealed myocarditis with areas of interstitial macrophages and fibrosis. The present case report links, for the first time, myocarditis with a human herpesvirus 6 subtype A infection and the appearance of apical ballooning.     

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 (1.5T Philips Intera CV) was performed before and within 24 hours after transcatheter ASD closure. Right atrial (RA) and left atrial (LA) dimensions, as well as right (RV) and left (LV) ventricular end-diastolic (ED) volumes were determined. Atrial size was assessed by planimetry of the maximum RA and LA areas in a standard four-chamber view, and ventricular volumes were calculated according to a modified Simpson's rule in short-axis views. RESULTS: The mean RA decreased significantly from 27.6 +/- 6.4 cm(2) before closure to 24.4 +/- 5.6 cm(2) after the procedure (P = 0.0018), whereas the LA area did not change (24.1 +/- 4.7 cm(2) vs. 23.8 +/- 5.2 cm(2), P = 0.76). The RV volumes, volume index, and ejection fraction (EF) decreased significantly from 229 +/- 64 mL to 181 +/- 43 mL (P < 0.001, average reduction = 19% +/- 15%), from 126.0 +/- 37.2 mL/m(2) to 96.6 +/- 28.6 mL/m(2) (P < 0.0001) and from 64 +/- 5% to 58% +/- 7% (P = 0.01), respectively. The LV volumes and volume index remained unchanged (114 +/- 25 mL vs. 118 +/- 22 mL, P = 0.18, 63.5 +/- 13.5 mL/m(2) vs. 63.0 +/- 17.4 mL/m(2), P = 0.83). Left-right shunting decreased from 40% +/- 15% to 9% +/- 15% (P < 0.001). CONCLUSION: Cardiac MRI can reveal detailed information on acute changes in shunt fraction and ventricular dimensions after ASD closure. ASD closure by percutaneous transcatheter device implantation results within 24 hours in a significant reduction of shunt fraction, RA and RV sizes, and RV function, whereas LA and LV dimensions remain unchanged.     

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. Furthermore, platelet adhesion to the endothelium is critical for the initiation of atherosclerotic lesion formation in vivo. Even prior to endothelial denudation, platelet adhesion governed by disturbed flow at predilection sites for atherosclerosis induces recruitment of proatherosclerotic cells and release of proinflammatory mediators from all involved cell types. Finally, the pathogenetic role of platelets for late atheroclerotic events including plaque rupture, microembolism or spasms within the microcirculation is well established. However, increasing evidence indicates that platelets mediate on the other hand potential regenerative mechanisms. Platelets recruit circulating progenitor cells to sites of vascular injury. Furthermore, they influence their biological activity and maturation. Therefore, platelets contribute at all stages of vascular disease by interfering with highly dynamic processes. Understanding interactions of platelets with other circulating cells and the vascular wall is a prerequisite to understand cardiovascular disease and to identify potential therapeutic targets.     

A comparative in vitro study of a magnetostrictive and a piezoelectric ultrasonic scaling instrument

BACKGROUND: The effects of magnetostrictive ultrasonic instruments and piezoelectric ultrasonic instruments on tooth surfaces seem to differ with regards to root debridement. AIM: The purpose of this study was to compare a magnetostrictive ultrasonic scaling instrument with a piezoelectric ultrasonic scaling instrument and a hand curette regarding time taken, calculus removal, tooth surface roughness (Ra), and SEM examination before and after instrumentation. METHODS: 30 extracted human teeth with subgingival calculus were assigned to one of three treatment groups (n=10). The working force was standardised for both ultrasonic instruments at 200 g and for the curette at 500 g. RESULTS: The results revealed that the time needed for instrumentation was 126.1+/-38.2 s for the curette, significantly more than for the piezoelectric ultrasonic instrument (74.1+/-27.6 s; p<0.05) and 104.9+/-25.4 s for the magnetostrictive ultrasonic instrument. Remaining calculus was similar for all three groups. The end Ra values were significantly worse for the piezoelectric instrument (2.02+/-0.41; p<0.05) compared to 1.42+/-0.48 for the curette and 1.36+/-0.41 for the magnetostrictive instrument. The SEM examination revealed the smoothest surfaces but, subjectively, the most tooth substance loss after the curette, followed by the magnetostrictive instrument, with the least substance loss, and then the piezoelectric instrument, with medium substance loss. CONCLUSION: The piezoelectric ultrasonic scaler was more efficient than the magnetostrictive ultrasonic scaler in removing calculus but left the instrumented tooth surface rougher.     

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. Platelets represent an important recruitment factor for circulating progenitor cells. Furthermore, they modulate progenitor cell chemotaxis, migration and differentiation. Platelets are crucial for the regeneration of parenchymatous organs such as the liver. Moreover, in the clinical setting, platelets are already applied for the restoration of connective and bone tissue. However, also adverse effects can be mediated by platelets and progenitor cells exposed to platelets, including the induction of pro-inflammatory processes. This review gives an update on platelets as regenerative cells and as modulators of progenitor cell biology in (patho-) physiological conditions. Abundant data obtained during the last decade have linked progenitor and stem cells to tissue repair. Very recent accumulating results from different groups revealed that platelets may have a strong influence on central functions of these progenitor cells. Only little is known about the impact of platelets themselves on tissue regeneration. Therefore, this review highlights the role of platelets themselves as a potential effector cell for tissue regeneration and their impact on progenitor cell biology.     

Novel role of the membrane-bound chemokine fractalkine in platelet activation and adhesion

Chemokines released by the endothelium have proaggregatory properties on platelets. Fractalkine, a recently discovered membrane-bound chemokine with a transmembrane domain, is expressed in vascular injury; however, the effects of fractalkine on platelets have not yet been investigated. Blood was taken from healthy Wistar-Kyoto rats and the expression of the fractalkine receptor on platelets was demonstrated. The modulation of surface expression of P-selectin was assessed by flow cytometry. P-selectin expression was significantly enhanced by in vitro stimulation with recombinant rat fractalkine compared with baseline levels. Selectively inhibiting the function of recombinant fractalkine by an antagonizing antibody or the disruption of the G-protein-coupled intracellular signaling cascade of the fractalkine receptor by pertussis toxin (PTX) completely prevented fractalkine-mediated platelet activation. Preincubation with apyrase significantly attenuated the fractalkine-induced degranulation. In a flow chamber model of platelet adhesion, stimulation with fractalkine significantly enhanced platelet adhesion to collagen and fibrinogen. Similar to P-selectin expression, enhanced adhesion could be prevented by the antagonizing antibody or preincubation of platelets with PTX. Fractalkine, which is overexpressed in atherosclerosis and vascular injury, contributes to platelet activation and adhesion and hence is likely to play a pathophysiologically important role for increased thrombogenesis in vascular diseases.