Fibrinogen promotes monocyte adhesion via a protein kinase C dependent mechanism

The accumulation of blood monocytes at sites of predilection of the vessel wall is an early cellular event of atherogenesis. Proteins of the vessel wall may facilitate monocyte adhesion and thus promote their recruitment. It has been shown that the relative content of extracellular fibrinogen increases during lesion development, and this study investigated the contribution of immobilized fibrinogen to monocyte adhesion and the underlying mechanism. Freshly isolated human blood monocytes were cultivated in serum-free RPMI 1640 in tissue culture wells precoated with albumin, fibrinogen, or fibrin. After 16 h the plates were washed and adherent cells enumcrated. Immobilized fibrinogen enhanced monocyte adhesion more than 1.9-fold compared to immobilized albumin or fibrin (P<0.05). Concomitant addition of the protein kinase C (PKC) inhibitors staurosporine or H7 suppressed monocyte adherence to immobilized fibrinogen but exerted no significant effect upon adhesion to any other surface tested. Stimulation of monocytes using phorbol myristate acetate resulted in increased binding of monocytes on fibrinogen but not on bovine serum albumin. When PKC activity was reduced through prolonged incubation with PMA for 16h, a significant reduction of monocyte adhesion on fibrinogen was observed. Peptides containing RGD sequences, which have been demonstrated to be ligands for certain integrins, did not inhibit monocyte adhesion. The data suggest that fibrinogen promotes monocyte adhesion in vitro by a PKC-dependent mechanism. PKC appears to be important not only for the initial cell adhesion but also for sustained binding of monocytes to fibrinogen.Abbreviations BSA Bovine serum albumin - ECM Extracellular matrix - PKC Protein kinase C - PMA Phorbol myristate acetate     

Increased primary success rate in coronary angioplasty using a guide wire with attached balloon (microprobe)

In 15 cases of 350 consecutive coronary angioplasties conventional low profile balloon catheters did not traverse the stenosis or occlusion over the guide-wire. A balloon on a wire device ("Microprobe", 2 mm) passed the stenosis or occlusion easily with a good primary result in 14 cases. The angioplasty procedure could then be completed with a larger standard balloon catheter. Use of the balloon on a wire device expands the technical facilities of angioplasty and increases the primary success rate in technically difficult cases.     

Cell death in ischemic,reperfused porcine hearts: A histochemical and functional study

Summary The temporal development of infarcts was histochemically and functionally determined in porcine hearts. In one series of experiments (22 pigs), the distal third of the left anterior descending coronary artery (LAD) was transiently occluded for periods between 20 and 90 min and was reperfused for another 24h. At the end of the experiments, the infarcted myocardium of four tissue slices was determined with a tetrazolium stain and related to the risk region which was delineated by a fluorescent dye. Infarcts started to develop in the ischemic septum and the subendocardial layer of the free anterior wall between 20 and 35 min of ischemia. Thereafter, infarctions progressed rapidly from the inner towards the outer layer at risk. The jeopardized anterior left ventricular wall became almost completely infarcted within 60 min of ischemia. In a second series of experiments (10 pigs) recovery of systolic shortening was studied with implanted ultrasonic crystals over 3 weeks of reperfusion. At the end of the experiments, systolic shortening was about 75% of baseline level when ischemia had lasted between 20 and 35 min. Almost no recovery was observed when the occlusion time lasted 45 to 60 min. This study suggests that the assessment of myocardial infarction with a tetrazolium stain after 24 h of reperfusion corresponds very well with functional recovery after 3 weeks of reperfusion. Furthermore, determination of regional myocardial function of the ischemic, reperfused segment in the chronic stage may be considered an additional tool to evaluate therapeutic effects on infarct size in this model.The study was supported by a grant of Deutsche Forschungsgemeinschaft (DFG) Sonderforschungsbereich 330 Organprotektion Göttingen.This paper contains parts of the Habilitationsschrift of Dr. H. H. Klein.