Abstract-Inflammatory response and chemotaxis of vascular wall cells play an important pathogenic role in the development of atherosclerosis. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant for monocytes. Besides the induction of monocyte recruitment, it has been suggested that MCP-1 may directly activate smooth muscle cells. We investigated whether MCP-1 affects the proliferation and cytokine production of human vascular smooth muscle cells (VSMCs) and determined the underlying signal transduction pathways. Stimulation of VSMCs with MCP-1 induced proliferation and resulted in a concentration-and time-dependent release of the proinflammatory cytokine interleukin-6 (IL-6). Pretreatment with pertussis toxin, GF109203X, and pyrrolidine dithiocarbamate inhibited MCP-1-dependent IL-6 release, suggesting the involvement of G i proteins, protein kinase C, and nuclear factor-B (NF-B). MCP-1 also induced extracellular signal-regulated kinase, which, along with IL-6 release, was inhibited by pertussis toxin. Key Words: atherosclerosis Ⅲ monocyte chemoattractant protein-1 Ⅲ interleukin-6 Ⅲ nuclear factor-B Ⅲ activator protein-1
AimsMitral valve regurgitation plays a significant role in the aetiology and course of heart failure. We investigated the impact of the learning curve on outcomes after percutaneous mitral valve repair with MitraClip.
Methods and resultsOutcomes of the first 75 consecutive patients treated with MitraClip at our centre were stratified by subsequent treatment periods (25 patients each). Median total procedure time and device time decreased from 180 and 105 min in period 1 to 95 and 55 min in period 3 (P , 0.005 each). There was an excess of total safety events in period 1 (n ¼ 16) that decreased in periods 2 and 3 (n ¼ 6 and 3, P ¼ 0.0003). Acute procedural success [APS; clip successfully placed and mitral regurgitation (MR) grade ≤2+ at discharge] was 80% in periods 1 and 2, but 92% in period 3 (P ¼ 0.46). At 6 months, improvement in durability and completeness of mitral valve repair was evident: 89.4% of patients in period 3 and 65.0% in period 1 had MR ≤2+ at 6 months (P ¼ 0.03). Within 30 days, no patient sustained myocardial infarction or stroke, and mortality was 2.7% for all patients without significant differences regarding periods. Furthermore, while treatment period did not affect mid-term survival and hospitalization for heart failure, failure of APS, STS (Society of Thoracic Surgeons) score ≥15%, and overt right heart failure at baseline predicted increased mortality.
ConclusionMitraClip showed a learning curve regarding mid-term durability and completeness of mitral valve repair, and APS predicted mortality. Recently published studies should be interpreted in consideration of these findings.--
Objective: To evaluate the diagnostic accuracy of 16 slice computed tomography (CT) in determining plaque morphology and composition in an experimental setting. The results were compared with histopathological analysis as the reference standard. Methods: Nine human popliteal arteries derived from amputations because of atherosclerotic disease were investigated with multislice spiral CT (MSCT). Atherosclerotic lesions were morphologically classified (completely or partially occlusive, concentric, eccentric), and tissue densities were determined within these plaques. In addition, vessel dimensions were quantitatively measured. Conclusions: 16 slice CT was found to be a reliable non-invasive imaging technique for assessing atherosclerotic plaque morphology and composition. Although calcified lesions can be differentiated from non-calcified lesions, the diagnostic accuracy in further subclassifying non-calcified plaques as lipid rich and fibrotic is low, even under experimental conditions.
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