SummaryA group of 100 patients with intermittent claudication (70 male, 30 female), treated with 100 mg ASA per day, were followed over 18 months after elective percutaneous balloon angioplasty. Platelet function was monitored over a period of 12 months by corrected whole blood aggregometry (CWBA). Upon stimulation by arachidonic acid (AA), adenosine diphosphate (ADP) and collagen, CWBA-results were obtained by an electronic acquisition and evaluation system correcting for hematocrit and platelet count of the blood sample.All patients showed a completely inhibited platelet response to AA stimulation. Comparison of the CWB A-results with clinical parameters revealed that reocclusions at the site of angioplasty occurred exclusively in male patients for which CWBA failed to prove an inhibition of aggregation upon both agonists, ADP and collagen, and for these patients the risk of complication is at least 87% higher (p = 0.0093).Only 40% of male patients show the expected effect of ASA on in vitro platelet aggregation at any given point in time and CWBA is capable of predicting those male patients which are at an elevated risk of reocclusion following peripheral angioplasty.

L-Arginine treatment decreased superoxide generation by cNOS while increasing NO accumulation, leading to protection from constriction (microvessel area, 17.77+/-0.95 versus 11.66+/-2.21 microm2 untreated, P<.0005) and reduction of edema after reperfusion (interfiber area, 16.56+/-2.13% versus 27.68+/-7.70% untreated, P<.005).

Findings suggest that mesenchymal progenitor cells can support the process of blood vessel formation, which may be relevant during granulation tissue formation at defect sites. The aim of this study was to investigate possible mechanisms of the angiogenic process that can be stimulated by mesenchymal progenitor cells. In the in vivo-like model of the chick embryo chorioallantoic membrane assay, we observed blood vessel ingrowth into collagen sponges containing conditioned medium from undifferentiated bone marrow stromal cells. In the Boyden chamber assay, the conditioned medium was chemotactic for human umbilical vascular endothelial cells and human uterus microvascular endothelial cells, and when cells were placed on Matrigel-coated culture dishes, formation of tubular structures was enhanced. The presence of vascular endothelial growth factor-neutralizing antibodies did not affect the outcome of the two in vitro assays. Bone marrow stromal cell-conditioned medium had no effect on proliferation of endothelial cells, as determined by measuring [3H]thymidine incorporation, and on matrix metalloproteinase 2 expression, as evaluated by reverse transcription-polymerase chain reaction and gelatin zymography. These data indicate that mesenchymal progenitor cells can provide a local environment that supports the ingrowth of blood vessels into a defect site.

Background-To investigate the contribution of inflammation to postangioplasty lumen loss, we used an adenoviral gene therapy approach to inhibit the central inflammatory mediator nuclear factor-B (NF-B) by overexpression of its natural inhibitor, IB␣. Methods and Results-The adenovirus carrying human IB␣ was applied immediately after balloon dilatation by a double-balloon catheter in a rabbit iliac artery restenosis model. Immunohistochemistry of IB␣ revealed that mainly smooth muscle cells of the media but also cells of the adventitia were transduced and expressed the transgene IB␣ for Ն8 days. At this time point, intercellular adhesion molecule-1 (30%) and monocyte chemotactic protein-1 (50%) expression, as well as recruitment of macrophages into the wounded area (90%), were significantly reduced in IB␣-treated vessels. In addition, expression of inhibitor of apoptosis proteins was reduced and the percentage of apoptotic cells was increased compared with control-treated contralateral vessels. Animals killed 5 weeks after treatment exhibited a significantly reduced degree of lumen narrowing (PϽ0.02) on the side treated with adenovirus IB␣. The lumen gain of Ϸ40% was due to positive remodeling. Conclusions-From these data, we conclude that balloon angioplasty-induced activation of NF-B contributes to lumen loss likely via induction of an inflammatory response and a decrease in the rate of apoptosis. These data show for the first time that inflammation mediated by NF-B is involved in postangioplasty lumen narrowing. Specific and more potent inhibitors of NF-B might therefore be a useful therapeutic measure to improve clinical outcome after balloon dilatation. (Circulation. 2002;105:633-638.)Key Words: restenosis Ⅲ inflammation Ⅲ gene therapy Ⅲ nuclear factor-B Ⅲ apoptosis P ercutaneous transluminal balloon angioplasty, widely used in the treatment of obstructed atherosclerotic vessels, is hampered by restenosis in Ͼ40% of patients who initially are treated successfully. 1 The mechanisms implicated in the process of restenosis include growth factor-dependent activation of smooth muscle cell (SMC) proliferation, 2 protease-dependent migration of cells into the wounded area, cytokine-initiated matrix deposition, 3 and progression of the atherosclerotic disease itself. 1 Because inflammation is implicated in the development of atherosclerosis, we hypothesized that it might also contribute to postangioplasty vessel narrowing. The common factor driving the inflammatory response is the transcription factor NF-B. 4,5 In resting cells, NF-B is held in the cytosol by complex formation with its natural inhibitor, IB␣. 6 Upon stimulation, eg, by inflammatory cytokines, IB␣ is phosphorylated, ubiquitinylated, and degraded by the proteasome. 7 NF-B is in turn liberated and enters the nucleus to initiate transcription of adhesion molecules, 8 cytokines, and other inflammatory mediators, 4 as well as of the inhibitor of apoptosis proteins (IAP). 9 Activated NF-B has been found within human atherosclerotic lesions or after angiop...

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For prevention of DAIH the distal venous graft diameter is not important, while the local compliance of an autologous vein is a predictive factor for DAIH formation and thus long-term patency.

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