Increased Expression of Lamin A/C Correlate with Regions of High Wall Stress in Abdominal Aortic Aneurysms.

Background: Since aortic diameter is the most -significant risk factor for rupture, we sought to identify stress-dependent changes in gene expression to illuminate novel molecular processes in aneurysm rupture.

Materials And Methods: We constructed finite element maps of abdominal computerized tomography scans (CTs) of seven abdominal aortic aneurysm (AAA) patients to map wall stress. Paired biopsies from high- and low-stress areas were collected at surgery using vascular landmarks as coordinates.

Investigating the Effect of a Single Infusion of Reconstituted High-Density Lipoprotein in Patients with Symptomatic Carotid Plaques.

Background: Elevation of plasma high-density lipoprotein (HDL) cholesterol concentration reduces cardiovascular mortality and morbidity. HDLs have been shown to possess acute anti-inflammatory, antioxidant, and antithrombotic properties. We hypothesize that HDL therapy can acutely alter local and systemic manifestations of plaque instability.

Pioglitazone Identifies a New Target for Aneurysm Treatment: Role of Egr1 in an Experimental Murine Model of Aortic Aneurysm.

Peroxisome proliferator-activated receptor x03B3; agonists have been shown to inhibit angiotensin II (AngII)-induced experimental abdominal aortic aneurysms. Macrophage infiltration to the vascular wall is an early event in this pathology, and therefore we explored the effects of the peroxisome proliferator-activated receptor x03B3; agonist pioglitazone on AngII-treated macrophages. Using microarray-based expression profiling of phorbol ester-stimulated THP-1 cells, we found that a number of aneurysm-related gene changes effected by AngII were modulated following the addition of pioglitazone.

Elevation of plasma high-density lipoproteins inhibits development of experimental abdominal aortic aneurysms.

Objective: Patients with abdominal aortic aneurysms have lower concentrations of high-density lipoproteins (HDLs), leading us to investigate whether increasing plasma HDLs could influence aneurysm formation.

Methods And Results: Using the angiotensin II-induced hypercholesterolemic and the CaCl(2)-induced normocholesterolemic mouse model of AAA, we investigated the hypothesis that elevation of HDLs inhibits AAA. HDLs elevated before or at the time of AAA induction reduced AAA formation in both models but had no effect on early ruptures.

Rosiglitazone negatively regulates c-Jun N-terminal kinase and toll-like receptor 4 proinflammatory signalling during initiation of experimental aortic aneurysms.

Objective: Development and rupture of aortic aneurysms (AA) is a complex process involving inflammation, cell death, tissue and matrix remodelling. The thiazolidinediones (TZDs) including Rosiglitazone (RGZ) are a family of drugs which act as agonists of the nuclear peroxisome proliferator-activated receptors and have a broad spectrum of effects on a number of biological processes in the cardiovascular system. In our previous study we have demonstrated that RGZ has a marked effect on both aneurysm rupture and development, however, the precise mechanism of this is unknown.

Diabetes as a negative risk factor for abdominal aortic aneurysm - does the disease aetiology or the treatment provide the mechanism of protection?

There is strong epidemiological evidence that patients with diabetes have a lower incidence of abdominal aortic aneurysm. The precise mechanism of this negative association is unknown. Whilst a number of studies have supported the hypothesis that protection is a function of diabetes-mediated changes in the vascular extracellular matrix biology, there is also support for the idea that the treatment regimens used in diabetes may afford protection against AAA.

Comparative proteomics reveals a systemic vulnerability in the vasculature of patients with abdominal aortic aneurysms.

Introduction: Abdominal aortic aneurysms (AAA) are associated with inflammation, apoptosis, and matrix degradation. AAA tissue represents the end stage of disease, limiting its utility in identification of factors culpable for initiation of aneurysm development. Recent evidence suggests that AAAs are a local representation of a systemic disease of the vasculature.

Resident vascular progenitor cells.

Homeostasis of the vessel wall is essential for maintaining its function, including blood pressure and patency of the lumen. In physiological conditions, the turnover rate of vascular cells, i.e.

Gene expression profile of abdominal aortic aneurysm rupture.

To search for novel transcriptional pathways that are activated in abdominal aortic aneurysm rupture, cDNA microarrays were used to compare global mRNA expression at the aneurysm rupture edge to anterior sac, and selected results were confirmed using quantitative real-time-polymerase chain reaction (QRT-PCR). This study identified apoptosis, angiogenesis, and inflammation as potentially important participants during the process of aneurysm rupture.

Characterisation of progenitor cells in human atherosclerotic vessels.

Recent data from animal models has demonstrated that both endothelial and smooth muscle progenitor cells contribute to the development of atherosclerosis. However, no data exists concerning the presence of progenitor cells in human atherosclerotic vessels. In the present study, a range of normal and atherosclerotic human arteries were collected from patients undergoing coronary artery bypass surgery.

Adventitial progenitor cells contribute to arteriosclerosis.

Accumulating evidence indicates the involvement of vascular progenitor cells in the development of arteriosclerosis, including transplant arteriosclerosis, angioplasty-induced restenosis, vein graft atherosclerosis, and spontaneous atherosclerosis. Recently, it was found that the adventitia of the arterial wall contains a large number of progenitor cells, which can differentiate into smooth muscle cells in vitro and in vivo. These progenitor cells were able to migrate from the adventitia into the intima, where they accumulate to contribute to atherosclerotic lesions of vein grafts in apoE-deficient mice.

Association of high intracellular, but not serum, heat shock protein 70 with postoperative atrial fibrillation.

Background: Atrial fibrillation is a common arrhythmia, after cardiac surgery. Reperfusion injury and inflammation associated with cardiac surgery are thought to be involved in its pathogenesis. We hypothesized that cytoprotective effects associated with heat shock protein 70 (HSP70) could counteract these proarrhythmic insults.

Abundant progenitor cells in the adventitia contribute to atherosclerosis of vein grafts in ApoE-deficient mice.

Recent evidence indicates that vascular progenitor cells may be the source of smooth muscle cells (SMCs) that accumulate in atherosclerotic lesions, but the origin of these progenitor cells is unknown. To explore the possibility of vascular progenitor cells existing in adults, a variety of tissues from ApoE-deficient mice were extensively examined. Immunohistochemical staining revealed that the adventitia in aortic roots harbored large numbers of cells having stem cell markers, e.

Thrombosis and neointima formation in vein grafts are inhibited by locally applied aspirin through endothelial protection.

Vein graft failure within the first month after bypass surgery is largely because of thrombosis. However, systemic study of thrombus formation in vein grafts is still lacking, and few effective techniques are available to prevent this event. Herein, we analyzed the kinetics of thrombosis and tested the effectiveness of locally applied aspirin on prevention of the disease in a mouse model.

Mouse model for hereditary hemorrhagic telangiectasia has a generalized vascular abnormality.

Background: Mutations in endoglin or activin like kinase-1, both involved in the endothelial transforming growth factor-beta signaling pathway, cause the autosomal dominant bleeding disorder hereditary hemorrhagic telangiectasia. We and others have reported mouse models for this disease that share the characteristic phenotype of dilated vessels and sporadic hemorrhage. The reasons for the variable phenotype in hereditary hemorrhagic telangiectasia are not understood.