Increased levels of CD34+ cells are associated in patients with abdominal aortic aneurysms compared with patients with peripheral vascular disease (original) (raw)
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International Journal of Cardiology, 2013
Aim: Circulating endothelial progenitor cells (EPCs) are associated with coronary artery disease (CAD) and predict its outcome. Although the pathophysiology of abdominal aortic aneurysm (AAA) is different, it shares some risk factors with CAD. Therefore, the correlation between EPCs and AAA was investigated. Methods and results: Seventy-eight subjects (age 77.2 ± 7.8 years) with suspected AAA were prospectively enrolled. Cut-off values (men, 3.5-5.5 cm; women, 3-5 cm) were used to define normal aorta, small AAA, and large AAA on thoraco-abdominal computer tomography. Endothelial function was measured by flow-mediated vasodilation (FMD). Flow cytometry and colony-forming units (CFUs) were used to evaluate circulating EPC numbers. Circulating EPCs were defined as mononuclear cells with low CD45 staining and double-positive staining for KDR, CD34, or CD133. Late out-growth EPCs were cultured from six patients with large AAAs and six age-and sex-matched controls to evaluate proliferation, adhesion, migration, tube formation, and senescence. FMD was significantly lower with large (5.26%± 3.11%) and small AAAs (6.31%± 3.66%) than in controls (8.88%± 4.83%, P =0.008). Both CFUs (normal 38.39± 12.99, small AAA 21.22± 7.14, large AAA 6.98± 1.97; P =0.026) and circulating EPCs (CD34 + /KDR + and CD133 + /KDR + ) were significantly fewer in AAA patients than in controls. On multivariate analysis, CFUs and circulating EPCs (CD34 + /KDR + ) were independently, inversely correlated to AAA diameter. Proliferation, adhesion, migration, tube formation, and senescence of late EPCs were significantly impaired in AAA patients. Conclusion: The number and function of EPCs were impaired in AAA patients, suggesting their potential role in AAA.
Reduced Immunoregulatory CD31+ T Cells in Patients With Atherosclerotic Abdominal Aortic Aneurysm
Arteriosclerosis, Thrombosis, and Vascular Biology, 2005
Background-Cell-mediated immunity is considered to contribute to the pathogenesis of abdominal aortic aneurysms (AAA). In particular, infiltrating macrophages and CD8 ϩ T lymphocytes participate in the destruction of the aortic wall extracellular matrix and smooth muscle cells. We surmise that these pathological events are controlled by circulating regulatory lymphocytes. Methods and Results-Circulating CD4 ϩ /CD31 ϩ cells were reduced in AAA patients (nϭ80, 8.9Ϯ0.6%) as compared with controls (nϭ69, 13.7Ϯ0.8%; PϽ0.001) and inversely proportional to AAA size. Exclusion of the aneurysm by an endoprothesis did not affect CD31 ϩ T cell values. Reduction of blood CD4 ϩ /CD31 ϩ cells was not attributable to their enrichment in AAA tissue. In contrast, CD8 ϩ /CD31 ϩ cells were slightly reduced in the blood while increased in the aneurysmal tissue (29.2Ϯ0.5 versus 20.2Ϯ4.7% in blood, nϭ6; PϽ0.05). Remarkably, high percentages of CD4 ϩ / CD31 ϩ cells were able to regulate proliferation and cytokine production of CD8 ϩ lymphocytes, as well as CD8 ϩ cell-mediated cytotoxicity of aortic smooth muscle cells (PϽ0.01). Finally, CD4 ϩ /CD31 ϩ cells reduced the production and activity of metalloproteinase-9 by lipopolysaccharide-stimulated macrophages.
High Prevalence of Circulating CD4+CD28- T-Cells in Patients With Small Abdominal Aortic Aneurysms
Arteriosclerosis, Thrombosis, and Vascular Biology, 2005
Objective-To assess the possible role of proinflammatory CD28 Ϫ T cells in abdominal aortic aneurysms (AAAs). Animal studies and human tissue studies suggest a role for interferon (IFN)-␥-producing T cells in the development and progression of AAAs. Methods and Results-Fluorescence-activated cells sorter analysis of peripheral blood samples and measurement of AAA size using sonography were performed in 101 AAA patients and 38 healthy controls. Peripheral percentages of CD28 Ϫ T cells of the CD3 ϩ CD4 ϩ and the CD3 ϩ CD8 ϩ were enriched in AAA patients with 7.8Ϯ8.8% and 41.9Ϯ15.7% compared with healthy controls with 2.2Ϯ6.1% and 24.9Ϯ15.5%, respectively (Pϭ0.002 and PϽ0.001, respectively). Both CD4 ϩ CD28 Ϫ and CD8 ϩ CD28 Ϫ T cells produced large amounts of IFN-␥ and perforin. Patients with small AAAs (Ͻ4 cm) showed higher peripheral levels of CD4 ϩ CD28 Ϫ T cells than those with larger AAAs (Pϭ0.025). Immunohistological examinations revealed 39.1Ϯ17.2% CD4 ϩ CD28 Ϫ and 44.0Ϯ13.8% CD8 ϩ CD28 Ϫ in AAA tissue specimens with inflammatory infiltrates.
European Journal of Cardio-Thoracic Surgery, 2011
Objective: Circulating endothelial progenitor cells (EPCs) are a specialized subset of stem/progenitor cells found in bone marrow. They participate in neo-vascularization of injured vessels and predict cardiovascular outcome in patient at risk. Several factors influence their migration and proliferation, among which is the widely studied stromal-derived factor-1a (SDF-1a). In cardiovascular disease, regarding thoracic aortic aneurysms (TAAs), few studies have investigated the levels of EPC and SDF-1a. As rupture, acute dissection and hematoma are acute complications of idiopathic ascending thoracic aortic aneurysm (iATAA) that increase with the size of aneurysm, we aimed to evaluate a potential relationship between circulating EPC and SDF-1a and iATAA size. Methods: The aneurysm size of 27 consecutive patients suffering from iATAA and scheduled for surgery was assessed by computed tomography scan. In all patients, we measured levels of circulating EPCs by flow cytometer, and plasma levels of SDF-1a the day before surgery. Results: The median aneurysm size was 54 mm (interquartile range (IQR): 50.0-58.8]. The EPC levels of CD34+/CD144+/CD14À and CD34+/VEGFÀR2+/CD14À were inversely correlated to aneurysm diameter ( p = 0.038, r = À0.424 and p = 0.0046, r = À0.65, respectively) before surgery. Conversely, plasma levels of SDF-1a were positively correlated to aneurysm size ( p = 0.042; r = 0.47). Conclusions: Our findings indicate that EPC levels may be useful for monitoring ascending aorta aneurysms and that SDF-1a could be a biomarker of iATAA expansion. #
Hemodynamic Regulation of CD34 + Cell Localization and Differentiation in Experimental Aneurysms
Arteriosclerosis, Thrombosis, and Vascular Biology, 2004
Objectives— Bone marrow-derived vascular progenitor cells (CD34 + ) are present in human and animal models of abdominal aortic aneurysm (AAA) disease. These preterminally differentiated cells may modulate disease resistance. We examined the influence of variable hemodynamic conditions on progenitor cell localization and differentiation in experimental AAAs. Methods and Results— Murine AAAs were created via porcine pancreatic elastase (PPE) infusion. AAA blood flow was increased by aortocaval fistula (ACF) formation (HF-AAA), decreased via left iliac ligation (LF-AAA), or left unchanged (NF-AAA). ACF creation increased flow by 1700%, whereas iliac ligation decreased flow 79% compared with baseline (0.6±0.1 mL/min). Wall shear stress (WSS) increased or decreased accordingly, and remained elevated (9.2±2.0 dynes/cm 2 ) in HF-AAA 14 days after PPE infusion. CD34 + cells were identified throughout the aortic wall in all flow conditions. Seven days after PPE infusion, HF-AAAs had more CD3...
The mechanism behind the incidence and the development of infrarenal aortic aneurysm and the factors affecting the rate of aortic dilatation remain largely unknown. The need for a biomarker capable to facilitate the diagnosis and the timed repair of an aortic aneurysm could reduce overall mortality. The aim of this study is to report on the potential predictive role of CD40L in aortic diameter growth and the development of AAA. The study group of 16 Wistar rats underwent a laparotomy and an infusion of porcine pancreatic elastase of the infrarenal aorta under hydrostatic pressure. The control group (n=16) underwent a sham procedure. At an interval of seven days, the animals of both groups underwent a laparotomy and the aortic dimension was measured. Blood samples were obtained at the same intervals. No significant change of the animals' weight was recorded. AAA was formed in all animals and aortic diameters differed significantly between the two groups. After the intervention, CD40L demonstrated a gradual increase in the study group and CD40L serum levels in this group were significantly higher compared to the control group; in parallel with the trend of aortic dilatation. CD40L could potentially act as biomarkers of the presence and development of infrarenal aortic aneurysms, but further studies with a larger number of animals are necessary.
Proinflammatory role of stem cells in abdominal aortic aneurysms
Journal of Vascular Surgery, 2014
The pathogenesis of abdominal aortic aneurysm (AAA) formation includes inflammation, vascular smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. That multipotent stem cells have an important role in cardiovascular health and disease has been well established, but the role of stem cells in aortic structural deterioration is poorly defined. We sought to describe the presence of stem cells in human AAA tissue and also investigated the differentiation of stem cells within the aneurysmal aorta. Methods: Infrarenal aortic wall specimens were collected from patients (n [ 7) undergoing open AAA surgical repair. Nonaneurysmal infrarenal aortic control samples (n [ 4) were collected at autopsies. Using immunohistochemistry, we compared the abundance of Stro1-positive (D), c-kit D , and CD34 D cells in aortic tissue. Using double-immunofluorescence staining, we evaluated stem cell differentiation into smooth muscle cells (SM22), fibroblasts (FSP1), and macrophages (CD68). We then investigated the colocalization of CD68 D cells with the cellular marker of proliferation Ki67. Results: The media and adventitia of infrarenal AAA samples both demonstrated a significantly greater number of c-kit D and CD34 D cells compared with matched control nonaneurysmal aortic tissues; however, the abundance of Stro1 D cells was not significantly different between the groups. Using double-immunofluorescence staining, we identified that AAA stem cells express the macrophage marker CD68 but not the smooth muscle cell marker SM22 or the fibroblast marker FSP1. CD68 D cells within the aortic wall colocalized with the cellular marker of proliferation Ki67. Conclusions: Stem cells are significantly elevated in infrarenal AAA tissue compared with matched control aortic tissue. Our data also demonstrate that AAA stem cells express macrophage surface antigens but not smooth muscle cell or fibroblast markers. Furthermore, CD68 D cells within the aortic wall colocalized with the cellular marker of proliferation Ki67. These finding suggest an inflammatory/immune role of stem cells during AAA pathogenesis and raise the possibility of localized replenishment therapy within the aneurysm wall.
Markers of inflammation in men with small abdominal aortic aneurysm
Journal of Vascular Surgery, 2010
Background: Markers of inflammation and fibrin turnover are elevated in individuals with a large (>55 mm) abdominal aortic aneurysm (AAA). Fibrin degradation generates D-dimer, known to possess multiple proinflammatory effects, and levels are elevated during early AAA development. This study characterized the plasma inflammatory response during early AAA pathogenesis to determine the effect of D-dimer levels.
Thrombosis and Haemostasis
The pathogenesis of abdominal aortic aneurysm (AAA) involves a central component of chronic inflammation which is predominantly mediated by myeloid cells. We hypothesized that the local inflammatory activity may be reflected in systemic alterations of neutrophil and monocyte populations as well as in soluble factors of myeloid cell activation and recruitment. To establish their marker potential, neutrophil and monocyte sub-sets were measured by flow cytometry in peripheral blood samples of 41 AAA patients and 38 healthy controls matched for age, sex, body mass index and smoking habit. Comparably, circulating factors reflecting neutrophil and monocyte activation and recruitment were assayed in plasma. Significantly elevated levels of CD16+ monocytes, activated neutrophils and newly released neutrophils were recorded for AAA patients compared with controls. In line, the monocyte chemoattractant C-C chemokine ligand 2 and myeloperoxidase were significantly increased in patients' pl...
Annals of Medicine, 2015
Background-Abdominal aortic aneurysm (AAA) is characterized by inflammatory cell accumulation in AAA lesions that produce inflammatory cytokines and advance its pathogenesis. Peripheral cytokines may predict the degree or risk of AAA. Methods and Results-ELISA determined plasma interleukin-6 (IL6), IL10, IL17A, IFN-γ, and C-reactive protein (CRP) from 476 AAA patients and 200 controls. AAA patients had lower IL6, IFN-γ, IL10, IL17A, and higher CRP than controls. IL10 correlated positively with IFN-γ, IL17A, or IL6, but not CRP in control or AAA populations. IL10 associated negatively with systolic blood pressure, whereas CRP associated positively with diastolic blood pressure and body mass index. CRP was an independent AAA risk factor and correlated positively with aortic diameters before and after adjustments for other risk factors. IFN-γ, IL17A, and CRP correlated positively with cross-sectional AAA area after adjustment. IL10 correlated positively with AAA growth rate before and after adjustment. AAA patients with CRP levels above the median doubled the risk of death. Conclusions-Reduced IFN-γ, IL10, and IL17A in AAA patients, positive correlations of IFNγ and IL17A with cross-sectional AAA area, IL10 with AAA growth rate, and IL10 with IFN-γ and IL17A suggest combined Th1, Th2, and Th17 immune responses in human AAAs.