Evidence that dendritic cells infiltrate atherosclerotic lesions in apolipoprotein E-deficient mice

Earlier we reported that atherosclerotic lesions of apoE-deficient mice contained cells which stained positively with anti-S-100 antibody and that cells exhibiting the ultrastructural features of dendritic cells were present in the aortic lesions. These observations suggested that dendritic cells might be involved in mouse atherosclerosis. By employing DEC-205 and MIDC-8 antibodies specific for dendritic cells, the present study has established that dendritic cells indeed accumulate in atherosclerotic lesions of apoE-deficient mice. Finding dendritic cells infiltrating atherosclerotic lesions in apoE-deficient mice offers the possibility of investigating the migratory routes of dendritic cells and their involvement in T-cell activation

Identification of dendritic cells in aortic atherosclerotic lesions in rats with diet-induced hypercholesterolaemia

We have previously identified dendritic cells (DCs) in the intima of human large arteries. These vascular DCs are common in atherosclerotic lesions but their immature forms are also present in normal arterial intima. Pathophysiological studies on vascular DCs are limited because they have only been studied in human specimens obtained at operation or post-mortem. The aim of the current study was to determine whether DCs participate in the development of atherosclerotic lesions in hypercholesterolemic rats. Male Wistar rats were divided into a control (n=13) and experimental cohort (n=48). The experimental animals were fed an atherogenic diet and 1% saline, while the controls were fed standard rat cubes and water. The aortas were obtained from both groups at 10, 20, and 30 weeks following commencement of the diet. An en face immunohistochemical technique, routine section i m m u n o h i s t o c h e m i s t r y, and transmission electron microscopy were used to detect the presence of DCs in the aortas. Examination of the aortas showed that S100+ cells with dendritic cell morphology were present in the aortic intima of hypercholesterolemic rats. The S100+ DCs displayed immunopositivity for OX-62 and MHC Class II antibodies. Within various types of atherosclerotic lesions, these cells were clustered throughout the intima but were especially prominent around arterial branch-points where they co-localized with various cell types, including T-cells and macrophages. Ultrastructural analysis confirmed the presence of cells with characteristics typical of DCs. These features included the presence of a welldeveloped tubulovesicular system, dendritic processes, and a lack of secondary lysosomes and phagosomes. This study establishes the presence of DCs in the aortic intima of rats with diet-induced atherosclerosis. The presence of DCs in this model of experimental atherogenesis could provide a new approach to investigating the function of DCs and may help clarify the immune-inflammatory mechanisms underlying atherosclerosis

Decreased expression of liver X receptor-α in macrophages infected with chlamydia pneumoniae in human atherosclerotic arteries in situ

10.1159/000327522Journal of Innate Immunity35483-49

Supplementary Material for: Increased Shedding of Microvesicles from Intimal Smooth Muscle Cells in Athero-Prone Areas of the Human Aorta: Implications for Understanding of the Predisease Stage

<b><i>Objective:</i></b> This study evaluated whether a change in the content of matrix microvesicles might occur at the preatherosclerotic stage. <b><i>Methods:</i></b> Applying quantitative electron microscopic and immunohistochemical analyses, two areas of grossly normal segments of the thoracic aorta were compared: atherosclerosis-prone (AP) areas, situated at the dorsal aspect of the aorta along the rows of intercostal branch origins, and atherosclerosis-resistant (AR) areas, situated at the corresponding sites of the ventral aspect of the aorta. <b><i>Results:</i></b> The electron microscopic analysis showed that there were 1.4 times more microvesicles in AP areas than AR areas (p = 0.019). It was found that matrix microvesicles originated as a result of blebbing and shedding of surface membranes of smooth muscle cells. A quantitative analysis of the expression of ADP-ribosylation factor 6 (ARF6), which is known to be involved in membrane trafficking and microvesicle formation, showed that ARF6 expression was 1.3 times higher in AP areas than that in AR areas (p = 0.006). There was a positive correlation between the content of matrix microparticles and the expression of ARF6 by intimal smooth muscle cells (r = 0.61; p < 0.0001). <b><i>Conclusion:</i></b> The present study supports the concept that alterations of the arterial intima occur at the predisease stage

Dendritic cells in the arterial wall express C1q: Potential significance in atherogenesis

10.1016/S0008-6363(03)00345-6Cardiovascular Research601175-186CVRE

Peroxisome proliferator-activated receptor (PPAR) gamma in cardiovascular disorders and cardiovascular surgery

Peroxisome proliferation-activated receptor gamma (PPAR\u3b3) is a nuclear receptor regulating transcription of several genes involved mainly in fatty acid and energy metabolism. PPAR\u3b3 agonists are used as insulin sensitizers for treatment of diabetes. However, according to the results of recent studies, their clinical application can be broadened. Activation of PPAR\u3b3 has a wide spectrum of biological functions, regulating metabolism, reducing inflammation, influencing the balance of immune cells, inhibiting apoptosis and oxidative stress, and improving endothelial function. These effects appear to be beneficial not only in diabetes and atherosclerosis, but also in a number of other conditions, including cardiovascular surgical interventions. In this review we discuss the role of PPAR\u3b3 in various conditions associated with cardiovascular risk, including diabetes mellitus, atherosclerosis, and hypertension, and will focus on current applications of PPAR\u3b3 activators and their therapeutic use. We will also give an overview of the potential use of PPAR\u3b3 agonists in cardiovascular surgical intervention

Detection of Chlamydophila pneumoniae in dendritic cells in atherosclerotic lesions

Atherosclerosis1732185-195ATHS

Supplementary Material for: Mitochondrial Aging: Focus on Mitochondrial DNA Damage in Atherosclerosis - A Mini-Review

Atherosclerosis is a complex disease which can be described as an excessive fibrofatty, proliferative, inflammatory response to damage to the artery wall involving several cell types such as smooth muscle cells, monocyte-derived macrophages, lymphocytes, dendritic cells and platelets. On the other hand, atherosclerosis is a typical age-related degenerative pathology, which is characterized by signs of cell senescence in the arterial wall including reduced cell proliferation, irreversible growth arrest and apoptosis, increased DNA damage, the presence of epigenetic modifications, shortening of telomere length and mitochondrial dysfunction. The most prominent characteristics of mitochondrial aging are their structural alterations and mitochondrial DNA damage. The mechanisms of mitochondrial genome damage in the development of chronic age-related diseases such as atherosclerosis are not yet well understood. This review focuses on the latest findings from studies of those mutations of the mitochondrial genome which may play an important role in the development of atherosclerosis and which are, at the same time, also markers of mitochondrial aging and cell senescence

Expression of GM3 synthase in human atherosclerotic lesions

10.1016/j.atherosclerosis.2005.04.019Atherosclerosis184163-7