Angioplasty, inflammation, and antiplatelet agents.
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Angioplasty, Balloon, Coronary↗
Biomedical subjects
Marc S Penn
Publications and source records attributed to Marc S Penn.
Administration of recombinant P-selectin glycoprotein ligand Fc fusion protein suppresses inflammation and neointimal formation in Zucker diabetic rat model.
OBJECTIVE: P-selectin-mediated leukocyte-endothelium and leukocyte-platelet interaction has been reported after vascular injury and has been correlated with neointimal hyperplasia, but its role in neointimal formation after arterial injury in diabetes has not been described. METHODS AND RESULTS: Using a Zucker diabetic rat balloon injury model, we examined the role of P-selectin in the vascular inflammatory process and neointimal formation after balloon injury. Immunohistochemistry revealed that P-selectin was intensely expressed and that CD45-positive leukocyte infiltration was significantly increased after arterial injury. A single preprocedural intravenous administration of a recombinant P-selectin-soluble glycoprotein ligand-Ig inhibited CD45-positive leukocyte accumulation and suppressed neointimal formation in the Zucker diabetic rat model. CONCLUSIONS: These results suggest that reduction of P-selectin-mediated leukocyte activation with the use of recombinant P-selectin-soluble glycoprotein ligand-Ig decreases the inflammatory response and limits neointimal formation after balloon injury in diabetes.
Animals↗
Increased tissue factor expression predicts development of cardiac allograft vasculopathy.
BACKGROUND: Cardiac allograft vasculopathy (CAV) limits the long-term success of cardiac transplantation. The incidence of CAV is increased in patients with elevated plasma levels of oxidized lipids or fibrin deposition within right heart biopsy (RHB) specimens. The present study investigated whether tissue factor (TF), the expression of which is regulated by oxidized lipids, is upregulated in patients with CAV. METHODS AND RESULTS: A TF score was developed to quantify TF expression in RHB specimens from 63 consecutive patients undergoing routine annual posttransplantation RHB and coronary angiography. In patients >2 years (3.0+/-0.8 years) posttransplantation (n=35), a high TF score was observed with greater frequency (75% versus 26%, P<0.004) in patients with CAV than those without CAV. In patients <2 years (0.87+/-0.48 years) posttransplantation (n=28) without evidence of CAV, the TF score was determined and patients were followed up prospectively. A high TF score had a positive predictive value of 78.6% for the development of CAV, and a low TF score had a negative predictive value of 100%. CONCLUSIONS: These data demonstrate that early TF expression predicts subsequent development of CAV. Increased TF expression could link the elevated levels of oxidized LDL and fibrin deposition known to precede CAV. These findings suggest that TF may play a role in the pathophysiology of CAV and could offer a potential prognostic tool and a novel target for the prevention of CAV, possibly with antioxidants or inhibitors of the TF pathway.
Adult↗
Targeted gene therapy for the treatment of cardiac dysfunction.
Congestive heart failure (CHF), one of the leading cardiovascular disorders in developed countries, remains a significant therapeutic challenge. Efficacious therapies are few, and the incidence of CHF and associated death rates continue to rise. An interest in the novel therapeutic approach of gene therapy for the treatment of CHF has emerged. Essential elements of successful gene therapy include an appropriate vector for delivering and expressing the gene within the target cell, an optimal protocol for delivery of the gene, and the identification of relevant pathways and molecular targets. Interest in gene therapy for CHF has been directed towards improving cardiomyocyte function through optimization of calcium homeostasis and beta-adrenoreceptor function, and preclinical studies have shown encouraging results. This review will discuss the vectors and mechanisms of gene delivery as well as potential molecular targets for the treatment of CHF.
Adenoviridae↗
Bacterial endocarditis and functional mitral stenosis: a report of two cases and brief literature review.
Mitral valve endocarditis typically results in mitral regurgitation. However, endocarditis leading to functional mitral stenosis is uncommon and, when present, fungal organisms are typically implicated. Thus, obstructive-type bacterial endocarditis due to large vegetations blocking the mitral valve orifice is a rare occurrence, with approximately 20 reported cases in the literature. We report on two patients with bacterial endocarditis and severe functional mitral stenosis requiring emergent surgery. Additionally, this is the first report of vancomycin-resistant enterococcus causing endocarditis and functional mitral stenosis. The discussion emphasizes the hemodynamic instability of these patients and need for early surgical intervention.
Endocarditis, Bacterial↗
Recombinant soluble P-selectin glycoprotein ligand-Ig (rPSGL-Ig) attenuates infarct size and myeloperoxidase activity in a canine model of ischemia-reperfusion.
The role of P-selectin in the process of reperfusion injury was evaluated using a recombinant soluble P-selectin glycoprotein ligand-Ig (rPSGL-Ig) in a canine coronary artery balloon occlusion model. rPSGL-Ig (1 mg/kg) or saline was given as an intravenous bolus 15 min before balloon deflation. Balloon occlusion time was 90 min followed by either 120 min or 7 days reperfusion. Infarct size was significantly reduced in the treatment group when expressed either as percentage of the area at risk or as absolute infarct size. Histological analysis showed that extensive myocardial injury and neutrophil infiltration were reduced by rPSGL-Ig. Myeloperoxidase activity (MPO) was significantly reduced in the risk area in the rPSGL-Ig group. Left ventricular ejection fraction was significantly less impaired during the first 24 h after reperfusion in the rPSGL-Ig group, although there was no difference by 7-day follow-up. Thus, administration of rPSGL-Ig decreases myocardial injury and inflammatory response for at least 7 days after reperfusion of ischemic myocardium.
Animals↗
Autologous cell transplantation for the treatment of damaged myocardium.
Autologous cell transplantation for the treatment of damaged myocardium after myocardial infarction is becoming an increasingly promising strategy. This form of treatment can be divided into 2 treatment strategies: The first uses differentiated cell types to replace the scarred tissue with living cells, while the second strategy uses stem cells in an attempt to regenerate myocardium. Over the past decade, multiple cell types have been used in animal studies, and clinical trials to determine the safety of injecting and engrafting skeletal myoblasts into damaged myocardium are presently being conducted. Animals studies focused on using stem cells to regenerate damaged myocardium have shown a naturally occurring reparative process that consists of up-regulation of progenitor cell release from the bone marrow after myocardial infarction, homing of these cells to the injured tissue, and differentiation of these progenitor cells into vascular cells and cardiac myocytes within the infarcted tissue. Unfortunately, this process occurs with great infrequency. Strategies to regenerate myocardium with stem cells either extract stem cells from the bone marrow and inject these cells into the damaged area or they attempt to increase the efficiency of the natural reparative process by increasing the mobilization of bone marrow-derived stem cells after myocardial infarction. This review summarizes the field of cell transplantation over the past decade, discusses areas of controversy, and proposes an outline of advancements that need to be made in both the clinical and scientific arenas for autologous cell transplantation to fully reach its clinical potential.
Animals↗