Interleukin-1 beta (IL-1 beta) is known to have a number of effects on the different cell types present within coronary arteries. In this study we identified the location and phenotype of cells containing IL-1 beta in human coronary artery specimens from patients suffering from either coronary atherosclerosis or cardiomyopathy and correlated the presence of IL-1 beta with disease severity. Luminal endothelial cells, adventitial vessel wall cells, and macrophages were double labeled immunohistochemically for IL-1 beta protein and a cell type-specific monoclonal antibody for either endothelial cells or macrophages. In situ hybridization was performed to locate the presence of IL-1 beta mRNA within the coronary artery wall. In this study IL-1 beta protein was found to be increased in the adventitial vessel walls of atherosclerotic coronary arteries compared with coronary arteries from nonischemic cardiomyopathic hearts. This increase was directly proportional to the severity of coronary atherosclerosis. IL-1 beta protein was also detected in luminal endothelium and macrophages of atherosclerotic coronary arteries and coronary arteries from nonischemic cardiomyopathic hearts. IL-1 beta mRNA was found in luminal endothelial cells, adventitial vessel endothelial cells, and macrophages. We conclude that IL-1 beta is produced by endothelial cells and macrophages in coronary arteries from ischemic hearts and to a lesser extent from nonischemic cardiomyopathic hearts.

In patients undergoing routine first-time cardiac surgery in an institution with a rigorous blood conservation program, the routine use of cell salvage does not further reduce the proportion of patients exposed to allogeneic blood transfusion. However, patients who do not have excessive bleeding after surgery receive significantly fewer units of blood with cell salvage. Although the use of cell savage may reduce the demand for blood products during cardiac surgery, this comes at an increased cost to the institution.

Objective-Failure of saphenous vein grafts remains a major limitation of coronary bypass surgery. The aims of the present study were to determine whether pressure distension of human saphenous vein induces the activation of p38-MAPK and to determine its role in apoptosis. Methods and Results-Phosphorylated p38 was detected at basal levels in human saphenous vein obtained immediately after harvesting. Distended saphenous vein showed significantly higher levels of phosphorylated p38 compared with control vein (PϽ0.01) and nondistended saphenous vein maintained for 3 and 6 hours after harvesting (both PϽ0.01 A utologous saphenous vein (SV) is the commonest conduit used for peripheral and coronary artery bypass grafting. However, 30% to 50% of vein grafts become occluded by 10 years. 1 The causes of vein graft occlusion are thrombosis in the early stages, and later the proliferation and migration of intimal smooth muscle cells along with the deposition of extracellular matrix leading to myointimal hyperplasia. 1 The precise cellular mechanisms involved in these processes remain unclear; however, surgical trauma to the vessel, including the stretch that occurs during manual distension before implantation, as well as implantation of the vein into the arterial circulation may be important.Apoptosis is reported to occur in pathological SV grafts, where it is thought to be involved in the transformation of a smooth muscle cell-rich myointimal thickening toward a fibrous cell-poor intimal thickening. 2,3 Apoptosis has also been shown to occur in tissue remodeling, associated with longitudinal stretch (axial strain) in rabbit carotid arteries. 4 We have previously shown that apoptosis is induced in pressure-distended human SV and is associated with increased vessel wall expression of the transcription factor c-fos, a downstream component of various signaling cascades. 5 In cultured porcine vascular smooth muscle cells (VSMCs), cyclic stretch has been shown to cause an increase in apoptosis, accompanied by a sustained activation of the mitogen-activated protein kinases (MAPK) JNK and p38. 6 In vitro studies using cultured smooth muscle cells have shown that mechanical stretch can activate ras/rac/p38 signal pathways 7 and p38 phosphorylates p53, which is responsible for mechanical stress-induced apoptosis. 8 In addition, the application of biomechanical stress has been shown to increase apoptosis in mouse vein grafts, and this occurs via p38 activation. 9 MAPKs are proline-directed serine/threonine kinases activated by dual phosphorylation on threonine and tyrosine residues in response to a wide variety of extracellular stimuli. The JNK and p38 MAPK signaling cascades are activated in response to cellular stress and certain cytokines via the activation of G protein coupled receptors 10 and are known to be involved in apoptosis. 11 Overexpression of MAPKs upstream of p38, such as MKK-3, leads to sustained activation of p38 and apoptosis. 12,13 However, ERK-MAPK is downregulated during apoptosis and upregulated during cellula...

The Arg–Gly–Asp (RGD) peptide sequence is known as a cell recognition site for numerous adhesive proteins present in the extracellular matrix (ECM) and in blood. Whilst surface immobilized RGD groups enhance cell attachment, RGD components present in solution can effectively inhibit cell attachment by competing with endogenous ligands for the same recognition site. In contrast to the widely reported binding to cell integrin, this study demonstrates a new RGD feature: its inhibitive effect on fibrinogen adsorption. Through a combined analysis of spectroscopic ellipsometry, neutron reflection and dual polarization interferometry, we show that the kinetic process of fibrinogen adsorption as a model pro-coagulant at the silica/solution interface and in the absence of any cells can be substantially reduced by the addition of RGD in solution and that the extent of the reduction is dependent on the relative concentration of RGD.

A study was conducted to determine the relationship among oral dose, trough whole blood levels, graft survival, and side effects in sirolimus-treated allografted rats. The heterotopic heart allograft model using Brown Norway donors and Lewis rat recipients was used. Rats were dosed daily with sirolimus or vehicle until graft failure or up to a maximum of 28 days. Upon graft failure, rats were bled for measurement of trough blood levels of drug and tissues sent for histopathologic analysis. Sirolimus blood concentration correlated positively with dose and graft survival. Significant graft survival occurred at whole blood trough levels of 0.5 ng/ml achieved at the 0.3 mg/kg/day dose. Analysis of the concentration-effect data using a sigmoidal Emax model calculated a whole blood EC50 of 2.0 ng/ml for graft survival. With mean trough concentrations of 7 ng/ml and higher, grafts survived after cessation of drug treatment. At the 0.8 mg/kg/day dose, there was a significant decrease in body weight gain in the rats. Histopathologic examination of sirolimus-treated animals detected thymic and lymphoid atrophy, both considered pharmacologic extensions of sirolimus's immunosuppressive activity and focal myocardial degeneration, an exacerbation of a spontaneous occurring lesion. These results demonstrate that sirolimus prolongs graft survival in rat in a concentration dependent manner with therapeutic whole blood levels of about 10 ng/ml.