Transfer of endothelial progenitor and bone marrow cells influences atherosclerotic plaque size and composition in apolipoprotein E knockout mice.

Objective: Recent clinical trials use cell therapy with bone marrow (BM) cells or endothelial progenitor cells (EPCs) for ischemic syndromes. We explored the effect of BM cell- or spleen cell-derived EPC transfer on plaque size and stability markers in the apolipoprotein E knockout (apoE KO) mouse model.

Methods And Results: ApoE KO mice aged 10 weeks served as recipients.

A functional role for inducible costimulator (ICOS) in atherosclerosis.

Background: Lymphocytes appear to influence atherosclerosis by altering cytokine production. Whereas primary lymphocyte activation requires T cell receptor ligation, costimulatory signals also appear requisite for generation of a functional T cell response. Inducible costimulator (ICOS) is a newly discovered T cell molecule with a dual role in immune mediated disorders.

The involvement of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in atherosclerosis.

Objectives: Herein, we determined the significance of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in atherosclerotic vascular disease.

Background: Inflammation is associated with the pathogenesis of atherosclerosis. The TNF-related apoptosis-inducing ligand/APO-2L, a member of the TNF superfamily, has a role in apoptosis induction and is recognized for its immunomodulatory properties.

Overexpression of 15-lipoxygenase in the vascular endothelium is associated with increased thymic apoptosis in LDL receptor-deficient mice.

Background: 15-Lipoxygenase (15-LO) is a nonheme iron-containing enzyme that catalyzes the peroxidation of fatty acids. Herein, we studied the effect of 15-LO overexpression in the vascular endothelium on thymocyte apoptosis by evaluating thymuses from low-density lipoprotein receptor-deficient (LDL-RD) mice and LDL-RD/15-LO mice. Thymuses were evaluated by immunohistochemistry and by TUNEL whereas in vitro studies were carried out by employing freshly isolated thymocytes from the respective mice and evaluation of apoptosis by propidium iodide and annexin V cytometry.

Clinical characteristics of unexpected death among young enlisted military personnel: results of a three-decade retrospective surveillance.

Study Objective: To explore the causes of sudden and unexpected death in a young and healthy military population, to examine the various patterns of diseases associated with these tragic events, and to investigate the factors found to be associated with this grave outcome.

Design: We retrospectively investigated 151 cases of Israeli military personnel who died unexpectedly over a 30-year period. We collected all the available medical records, autopsy results, and investigation committee reports.

Army personnel satisfaction in different settings of primary health care clinics.

Purpose: To analyze patient satisfaction in Israeli Defense Forces primary care clinics (PCCs), and to compare different satisfaction indices that best correlate with general satisfaction index.

Methods: Large-scale patient satisfaction survey throughout all PCCs, classified as active front clinics, training schools clinics, and home front clinics.

Results: Participants (5,103) filled out standardized questionnaires.

Neurological dysfunction associated with antiphospholipid syndrome: histopathological brain findings of thrombotic changes in a mouse model.

The aim of this work was to study the pathological processes underlying neurological dysfunctions displayed by BALB/C mice induced with experimental antiphospholipid syndrome (APS), as we have previously reported. Experimental APS was induced in female BALB/C mice by immunization with a pathogenic monoclonal anticardiolipin (aCL) antibody, H-3 (n = 10), or an irrelevant immunoglobulin in controls (n = 10). Mice immunized with H-3 developed clinical and neurological manifestations of APS, including: embryo resorption, thrombocytopenia neurological defects and behavioral disturbances.

Evidence for the involvement of T cell costimulation through the B-7/CD28 pathway in atherosclerotic plaques from apolipoprotein E knockout mice.

Antigen-specific T cell activation is thought to influence the initiation and progression of the atherosclerotic plaque. For the T cell activation program to be functional, it is essential not only to facilitate T cell receptor engagement by antigen-presenting cells (APC), but also to deliver requisite costimulatory signals. The most widely comprehended costimulatory pathway involves the ligation of CD28 expressed on T cells by CD80 and CD86 upregulated on APCs.

Evaluating delivery of primary health care to military personnel during low-intensity conflict using a patient satisfaction survey.

The delivery of medical health care to soldiers serving in active front units in the Israeli Defense Forces requires the ability to adjust to different military activity settings. This study was conducted to compare patient satisfaction, as a tool for assessing quality of care, in different activity settings: training and Low-intensity conflict setting. A patient satisfaction survey was conducted simultaneously in battalions during low-intensity conflict and training activities.

The role of anti-endothelial cell antibodies in Kawasaki disease - in vitro and in vivo studies.

Kawasaki disease (KD) is a systemic vasculitis with cardiac and noncardiac complications. Anti--endothelial cell antibodies (AECA) are found among many patients with KD. The aim of this study was to investigate the pathogenic role of AECA in KD using in vitro and in vivo experimental models.

Functional inhibition of Ras by S-trans,trans-farnesyl thiosalicylic acid attenuates atherosclerosis in apolipoprotein E knockout mice.

Background: Atherosclerosis is a multifactorial disorder involving inflammatory processes. These responses are associated with robust activation of signaling cascades by diverse cell surface receptors in a variety of cell types. The processes that are involved in atherosclerosis would likely require intact Ras pathways, which play a key role in the control of cell growth, differentiation, and apoptosis.

12/15-Lipoxygenase gene disruption attenuates atherogenesis in LDL receptor-deficient mice.

Background: Human 15-lipoxygenase (LO) and its murine analogue 12/15-LO are capable of directly oxidizing esterified fatty acids in lipoproteins and phospholipids. Because these oxidized products possess atherogenic properties, it was suggested that LOs may be involved in enhancing atherogenesis. Previous in vivo tests of the role of LOs in atherogenesis animal models, however, have yielded conflicting results.

Cellular and humoral immune responses to heat shock protein 65 are both involved in promoting fatty-streak formation in LDL-receptor deficient mice.

Objectives: This study was designed to determine the role of cellular and humoral immune responses to heat shock protein 65 (HSP65) in murine atherosclerosis.

Background: Inflammatory processes appear to influence the progression of atherosclerosis. Immunization with HSP65 was previously shown to induce arteriosclerosis in rabbits and to enhance fatty-streak formation in mice.

Whole body hyperthermia accelerates atherogenesis in low-density lipoprotein receptor deficient mice.

The application of brief periods of heat stress prior to induction of various forms of tissue injury (ischemia-reperfusion, myocardial infarction, endothelial denudation) has been shown to result in preconditioning and attenuation of subsequent damage. Atherosclerosis represents a state of heightened response to injury at the level of the vessel wall, involving endothelial cells, smooth muscle cells, and macrophages. In the current study, we studied the effects of whole body hyperthermia (WBH) on diet-induced atherosclerosis in a murine model.

Tissue-specific gene therapy directed to tumor angiogenesis.

Gene therapy directed specifically to the vascular wall, particularly to angiogenic endothelial cells is a prerequisite in vascular disease treatment. Angiogenesis is a major feature in many pathological conditions including wound healing, solid tumors, developing metastases, ischemic heart diseases and diabetic retinopathy. In the present study we developed a tissue-specific gene therapy to the angiogenic blood vessels of tumor metastasis using an adeno-based vector containing the murine preproendothelin-1 (PPE-1) promoter.

Adoptive transfer of beta(2)-glycoprotein I-reactive lymphocytes enhances early atherosclerosis in LDL receptor-deficient mice.

Background: It has been proposed that autoimmune factors can influence the progression of atherosclerosis. We have previously shown that immunization of LDL receptor-deficient (LDL-RD mice) with beta(2)-glycoprotein I (beta2GPI; a principal target of "autoimmune" antiphospholipid antibodies) enhances early atherosclerosis. In the present study, we tested the hypothesis that adoptive transfer of beta2GPI-reactive T cells can accelerate fatty streak formation in LDL-RD mice.

Effect of hyperglycemia and hyperlipidemia on atherosclerosis in LDL receptor-deficient mice: establishment of a combined model and association with heat shock protein 65 immunity.

Diabetes and atherosclerosis have been proposed to be influenced by immune and autoimmune mechanisms. A common incriminated antigen in both disorders is the heat shock protein (HSP)-60/65. In the current study, we established a model combining hyperglycemia with hyperlipidemia in LDL receptor-deficient (LDL-RD) mice and assessed its possible influences on lipid profile, HSP60/65, and atherogenesis.

Requisite role for interleukin-4 in the acceleration of fatty streaks induced by heat shock protein 65 or Mycobacterium tuberculosis.

Atherosclerotic lesions can be induced in rabbits and mice immunized with heat shock protein 65 (HSP65). In the current study, we investigated the role of interleukin (IL)-4 in the HSP65- and Mycobacterium tuberculosis (MT)-induced models that exhibit an inflammatory phenotype. Fatty streak formation in IL-4-knockout (IL-4 KO) mice immunized with HSP65 or MT was significantly reduced when compared with lesions in wild-type C57BL/6 mice.

Autoimmunity in atherosclerosis: lessons from experimental models.

The modern view of atherosclerosis is of a chronic inflammatory disorder. In accord with this paradigm, the process of uninhibited influx of fat to the vessel wall results from an 'adequate' response to various forms of injury (i.e.

Immunization of low-density lipoprotein receptor deficient (LDL-RD) mice with heat shock protein 65 (HSP-65) promotes early atherosclerosis.

Heat shock proteins are a family of approximately 25 highly conserved proteins upregulated in response to various forms of stress. They play an active role in the development autoimmune diseases in animals, and have been incriminated in human autoimmune diseases (i.e.

Local complement genes expression in the mammary gland: effect of gestation and inflammation.

Complement components in breast milk may enhance the local immune response in the gut of infants. In this study, we investigated the expression of complement genes in the mammary gland and attempted to determine possible regulatory mechanisms. We have studied the expression of C3, C4, factor B, and HLA-DRalpha mRNA by in situ hybridization in gestational mammary gland specimens and compared these findings to those in breast tissue affected with an inflammatory process, lactating adenoma or idiopathic gynecomastia.

Proliferation, apoptosis and thymic involution.

The thymus reaches its maximal size at the age of 1 month in ICR mice and thereafter, the thymic cortex undergoes an exponential decline. This study was designed to compare the proliferation and apoptosis of thymocytes in different parts of the thymus of ICR female mice at the beginning and after the rapid phase of decline of the thymic cortical cellularity. The pattern of proliferation and apoptosis of the thymus was studied in situ in 1-month-old ICR female mice (10 mice) compared to mice at 7 months of age (10 mice).

Increased endothelial cell expression of alpha3beta1 integrin in cardiac valvulopathy in the primary (Hughes) and secondary antiphospholipid syndrome.

The objective of this work was to determine markers of endothelial cell activation in valves from patients with antiphospholipid syndrome (APS) and heart valve involvement, in order to establish a role for endothelial cells in the pathogenesis of the valvular disease. Sixteen valves from ten patients with APS, obtained from autopsies or removed during valve replacement, were studied. Two groups of valves were used as controls.

Immunolocalization of beta2-glycoprotein I (apolipoprotein H) to human atherosclerotic plaques: potential implications for lesion progression.

Background: beta2-Glycoprotein I (beta2GPI) is a major antigenic target of antiphospholipid antibodies, which possesses natural anticoagulant properties. The aim of the present study was to determine its presence and localization within human atherosclerotic plaques and to study its association with endothelial cells and monocyte macrophages in vitro.

Methods And Results: Human atherosclerotic lesions were obtained after carotid endarterectomies and studied immunohistochemically with anti-beta2GPI as well as antibodies to CD4/CD8, macrophages, and adhesion molecules.