ABSTRACT
Some recent reports suggested that elderly and female patients did not benefit from implantation of the second internal thoracic artery (ITA) during coronary artery bypass surgery (CABG). Macrophages, among other cells, were described to be involved in both atherosclerosis and aortocoronary grafts failure. The aim of the study was to examine the age and gender association with different distribution of CD68+ cells within the layers of ITA wall. This study involved 158 consecutive patients (95 male and 63 female), with the mean age of 64.5±9.5 years, who underwent elective CABG procedures. During surgery, the surplus distal segments of ITA were harvested for immunohistochemical analysis. The number and distribution of CD68+ cells was calculated and plotted against the age and gender of the study participants. CD68+ cells were present in all of the harvested ITA fragments (median 44), more in women (55) than in men (42) (p less than 0.001). However, this difference was of statistical significance exclusively in the tunica intima. Approximately 70% of macrophages were found in the tunica adventitia. The total number of CD68+ cells the in arterial wall as well as in the tunica intima and adventitia correlated positively with the age of patients (r=0.544, r=501 and r=0.462, respectively). The lack of significant advantages of the use of two thoracic arteries, in elderly patients and women, might have resulted from the larger population of CD68+ cells in their walls, especially the tunica intima. However, this result from immunohistochemical analysis needs validation in long-term clinical research on a larger cohort of patients.
Subject(s)
Coronary Artery Bypass/methods , Macrophages/immunology , Mammary Arteries/immunology , Adult , Age Factors , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Sex Characteristics , Tunica Intima/immunology , Tunica Intima/pathologyABSTRACT
INTRODUCTION: Immunological studies of giant cell arteritis (GCA) suggest that a triggering antigen of unknown nature could generate a specific immune response. We thus decided to detect autoantibodies directed against endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in the serum of GCA patients and to identify their target antigens. METHODS: Sera from 15 GCA patients were tested in 5 pools of 3 patients' sera and compared to a sera pool from 12 healthy controls (HCs). Serum immunoglobulin G (IgG) reactivity was analysed by 2-D electrophoresis and immunoblotting with antigens from human umbilical vein ECs (HUVECs) and mammary artery VSMCs. Target antigens were identified by mass spectrometry. RESULTS: Serum IgG from GCA patients recognised 162 ± 3 (mean ± SD) and 100 ± 17 (mean ± SD) protein spots from HUVECs and VSMCs, respectively, and that from HCs recognised 79 and 94 protein spots, respectively. In total, 30 spots from HUVECs and 19 from VSMCs were recognised by at least two-thirds and three-fifths, respectively, of the pools of sera from GCA patients and not by sera from HCs. Among identified proteins, we found vinculin, lamin A/C, voltage-dependent anion-selective channel protein 2, annexin V and other proteins involved in cell energy metabolism and key cellular pathways. Ingenuity pathway analysis revealed that most identified target antigens interacted with growth factor receptor-bound protein 2. CONCLUSIONS: IgG antibodies to proteins in the proteome of ECs and VSMCs are present in the sera of GCA patients and recognise cellular targets that play key roles in cell biology and maintenance of homeostasis. Their potential pathogenic role remains to be determined.
Subject(s)
Autoantibodies/immunology , Autoantigens/immunology , Endothelial Cells/immunology , Giant Cell Arteritis/immunology , Muscle, Smooth, Vascular/immunology , Proteomics/methods , Aged , Aged, 80 and over , Cell Line, Transformed , Cells, Cultured , Cytokines/immunology , Electrophoresis, Gel, Two-Dimensional/methods , Endothelial Cells/cytology , Female , Human Umbilical Vein Endothelial Cells , Humans , Immunoblotting/methods , Immunoglobulin G/immunology , Male , Mammary Arteries/cytology , Mammary Arteries/immunology , Mass Spectrometry/methods , Muscle, Smooth, Vascular/cytology , Receptors, Growth Factor/immunology , Vinculin/immunologyABSTRACT
BACKGROUND: The main aim of the present study was to compare the occurrence of inflammatory cell infiltrates in the aorta, a vessel with a high occurrence of atherosclerosis, with that in the saphenous vein (SV) and internal mammary artery (IMA), which are protected from atherosclerosis. METHODS AND RESULTS: Samples from the aorta, SV, and IMA of 65 patients with inflammatory rheumatic diseases (IRD) and from 51 control patients undergoing coronary artery bypass graft surgery were examined for the presence and location of inflammatory cell infiltrates and atherosclerotic lesions. Mononuclear cell infiltrates (MCIs) in the media or adventitia were observed in 2% IMAs, 17% SVs, and 35% aortic specimens (SV vs IMA: p=0.006; SV vs aorta: p=0.001). Atherosclerotic lesions were present in none IMA, 3% SVs and 18% aortic specimens. IRD and smoking increased the odds of MCI in the aorta (odds ratio (OR)=3.6, 95% confidence interval (CI): 1.6-8.5 and OR=4.0, 95% CI: 1.5-10.9), but not in the SV or IMA. CONCLUSIONS: The occurrence of medial and adventitial MCI in the aorta, SV, and IMA paralleled each vessel's susceptibility to atherosclerosis: it was highest in the aorta and lowest in IMA. Local vascular inflammation may be involved in atherogenesis, and influence the patency of vascular grafts.
Subject(s)
Aorta, Thoracic/immunology , Atherosclerosis/immunology , Coronary Artery Bypass , Coronary Artery Disease/immunology , Mammary Arteries/immunology , Rheumatic Diseases/immunology , Saphenous Vein/immunology , Aged , Aorta, Thoracic/pathology , Atherosclerosis/pathology , Biopsy , Calcinosis/immunology , Case-Control Studies , Coronary Artery Disease/pathology , Coronary Artery Disease/surgery , Female , Fibrosis , Humans , Male , Mammary Arteries/pathology , Middle Aged , Odds Ratio , Rheumatic Diseases/complications , Rheumatic Diseases/pathology , Rheumatic Diseases/surgery , Risk Assessment , Risk Factors , Saphenous Vein/pathology , Smoking/adverse effects , Tunica Intima/immunologyABSTRACT
Acute coronary syndromes (ACS) are characterized by multiple unstable coronary plaques and elevated circulating levels of inflammatory biomarkers. The endothelium of internal mammary arteries (IMA), which are atherosclerosis resistant, is exposed to proinflammatory stimuli as vessels that develop atherosclerosis. Our study investigated the IMA endothelial expression of inflammatory molecules in patients with ACS or chronic stable angina (CSA). IMA demonstrated normal morphology, intact endothelial lining, and strong immunoreactivity for glucose transporter 1. E-selectin expression was observed more frequently in IMA of ACS patiention than CSA patients (ACS 61% vs. CSA 14%, P = 0.01). High fluorescence for major histocompatibility complex (MHC) was significantly more frequent on the luminal endothelium (ACS 66.7% vs. CSA 17.6%, P = 0.001 for class I; and ACS 66.7% vs. CSA 6.2%, P = 0.0003 for class II-DR) and on the vasa vasorum (ACS 92.9% vs. CSA 33.3% and 7.7%, P = 0.0007 and P < 0.0001 for class I and class II-DR, respectively) of ACS patients than CSA patients. ICAM-1, VCAM-1, Toll-like receptor 4, tissue factor, IL-6, inducible nitric oxide synthase, and TNF-alpha expression were not significantly different in ACS and CSA. Circulating C-reactive protein [ACS 4.8 (2.6-7.3) mg/l vs. CSA 1.8 (0.6-3.5) mg/l, P = 0.01] and IL-6 [ACS 4.0 (2.6-5.5) pg/ml vs. CSA 1.7 (1.4-4.0) pg/ml, P = 0.02] were higher in ACS than CSA, without a correlation with IMA inflammation. The higher E-selectin, MHC class I and MHC class II-DR on the endothelium and vasa vasorum of IMA from ACS patients suggests a mild, endothelial inflammatory activation in ACS, which can be unrelated to the presence of atherosclerotic coronary lesions. These findings indicated IMA as active vessels in coronary syndromes.
Subject(s)
Acute Coronary Syndrome/metabolism , Angina Pectoris/metabolism , Arteritis/metabolism , Inflammation Mediators/analysis , Mammary Arteries/chemistry , Acute Coronary Syndrome/immunology , Acute Coronary Syndrome/pathology , Adult , Aged , Aged, 80 and over , Angina Pectoris/immunology , Angina Pectoris/pathology , Arteritis/immunology , Arteritis/pathology , E-Selectin/analysis , Endothelium, Vascular/chemistry , Female , HLA-DR Antigens/analysis , Histocompatibility Antigens Class I/analysis , Humans , Male , Mammary Arteries/immunology , Mammary Arteries/pathology , Microscopy, Confocal , Middle Aged , Up-Regulation , Vasa Vasorum/chemistryABSTRACT
Vascular smooth muscle is now recognized as an important site of mediator generation under inflammatory conditions. Indeed, the release of leukocyte activators, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-8, by human arterial smooth muscle cells has recently been demonstrated. However, the potential for venous cells to release GM-CSF has not been addressed. We have shown that human vascular smooth muscle cells express the "inflammatory" form of cyclooxygenase (COX), cyclooxygenase-2 (COX-2), when stimulated with cytokines. In some nonvascular cell types, the COX activity has been shown to regulate the release of GM-CSF and IL-8, although the nature of the isoform responsible was not addressed. We show that human venous smooth muscle cells, like their arterial counterparts, release GM-CSF after stimulation with IL-1beta. Similarly, both cell types released IL-8. Under the same conditions, we found that COX-2 activity suppressed GM-CSF, but not IL-8, release by both types of human vascular cells. Moreover, the prostacyclin mimetic, cicaprost, and the cAMP analogue, dibutyryl cAMP, inhibited GM-CSF release from these cells. These observations suggest that COX-2 activity suppresses GM-CSF release via a cAMP-dependent pathway in human vascular cells and illustrates a novel mechanism by which this enzyme can modulate immune and inflammatory events.