Induction of the Coxsackievirus and Adenovirus Receptor in Macrophages During the Formation of Atherosclerotic Plaques (original) (raw)
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Viruses in the etiology of atherosclerosis
Proceedings of the National Academy of Sciences, 1983
To examine the possible role of viruses in the etiology of atherosclerosis, we searched for the. presence of viral, genomes in arterial tissues by in situ hybridization. Because chickens infected with Marek disease virus, a herpesvirus, develop atherosclerotic lesions after infection, we looked for the presence of herpesvirus or parts thereof in human artery wall tissue, particularly in individuals with evidence of atherosclerosis. Herpesvirus probes were used on specimens of aortic wall removed from patients undergoing coronary bypass surgery. Evidence for the presence of herpes simplex viral mRNA was obtained in 13 specimens. Some of the specimens positive for herpes simplex virus appear to represent early stages in atherogenesis. Evidence for the presence of cytomegalovirus or Epstein-Barr viral genome was not observed in any of the specimens examined. We have also shown that herpes simplex virus can infect human fetal smooth muscle cells in culture. There are several ways in which viruses could operate in the pathogenesis of atherosclerosis: They could induce proliferation of artery wall intimal smooth muscle cells via injury or by genomic alterations leading to clonal expansion of intimal smooth muscle cell populations. We suggest that expression of at least a part of the herpesvirus genome in arterial smooth muscle cells may in some cases be instrumental in initiating or maintaining this enhanced cell proliferation. Furthermore, viral agents could explain other puzzling features in the occurrence of atherosclerosis and the attendant heart disease and strokes.
Genetic manipulation of macrophage—and vascular genes in mouse models of atherosclerosis
International Congress Series, 2004
Macrophage-derived foam cells play an essential role in the development of atherosclerosis. The population of macrophages in the arterial wall highly depends on monocyte infiltration from the blood circulation. Transplantation of the hematopoietic system offers a unique opportunity to replace genes in cells from hematopoietic origin, including macrophages. We have exposed atherosclerosis susceptible mice (LDL-receptor À / À , apoE À / À and apoE3-Leiden mice) to total body irradiation 1 day before the transplantation of donor bone marrow lacking either apoE, LDL-receptor, LRP, ABCA-1, LPL, CCR2, SR-BI or overexpressing SR-A, ApoE3-Leiden or apoE2. This allowed the evaluation of the individual role of these gene products in the development of atherogenesis.The evaluation of new strategies for the prevention of atherosclerotic lesion formation and plaque rupture has thus far been hampered by the lack of a practical animal model. A mouse model of rapid and site-controlled atherogenesis was developed by the placement of silastic collars around the carotid arteries of apoE À / À and LDL-R À / À mice, leading to rapid lesion development (3-6 weeks) proximal to the collar [Circulation 103 (2001) 1164]. Local transfection of the arteries with IL-10, PAF-AH or IL-9 led to inhibition of atherosclerotic lesion development, while administration of adenovirus p53 induced plaque rupture. Being the first example of inducible rupture at a predefined location, this model offers a unique opportunity to delineate the processes that precede rupture, as well as to evaluate plaque-stabilizing therapies.
Atherosclerosis, 2005
We have previously demonstrated that mouse cytomegalovirus (MCMV) infection aggravates atherosclerosis by stimulating the ongoing inflammatory process in the vascular wall. Here we investigated whether MCMV antigenic immune stimulation by UV-MCMV injection is sufficient to aggravate atherosclerosis. In addition we analyzed whether low viral doses are sufficient to stimulate atherosclerosis. Therefore, apoE −/− mice received a low dose injection with infectious virus (MCMV) or replication-deficient virus (UV-inactivated MCMV, UV-MCMV). Atherosclerosis progression, influx of inflammatory cells in atherosclerotic lesions and internal organs and the number of MCMV DNA copies in various organs were determined at 2 weeks after injection. After injection with infectious virus, MCMV DNA was present in internal organs, while no MCMV DNA could be detected after UV-MCMV injection. Interestingly, both MCMV and UV-MCMV significantly increased mean atherosclerotic lesion area and T cell number in the atherosclerotic lesions, while only MCMV infection increased T cell numbers in the internal organs. These data indicate that in apoE −/− mice both low dose infectious MCMV as well as MCMV antigenic injections are sufficient for atherosclerosis aggravation.
Archives of Medical Science - Atherosclerotic Diseases
Introduction: The most common etiologic factor of coronary artery disease (CAD), carotid artery disease, and peripheral artery disease is atherosclerosis. In our study, we aimed to show the effect of cytomegalovirus (CMV), which can occur almost everywhere in the human body, on triggering the chronic inflammatory process in the pathophysiology of atherosclerosis, and its presence and impact in the plaques leading to carotid artery stenosis. Material and methods: Thirty-six patients, who underwent carotid endarterectomy at the Department of Cardiovascular Surgery, Istanbul University Istanbul Medical Faculty between April 2017 and April 2018, were included in this study upon their consent. Patients with additional immunosuppressive conditions were not included in the study. Unilateral atheromatous plaque was preferred for patients undergoing bilateral carotid endarterectomy and all risk factors (DM, HT, hyperlipidemia, etc.) were evaluated together for all patients. Results: When the relationship between CMV (DNA) presence in samples taken from patients' plaques and sex, age and comorbidities was examined, CMV (DNA) positivity (45.8%) was significantly higher in DM patients than non-DM patients (8.3%) (p = 0.024). Likewise, CMV(DNA) positivity (40%) was significantly higher in HT patients than in non-HT patients (25%) (p = 0.008). CMV(DNA) positivity (63%) was significantly higher in patients with bilateral carotid artery stenosis than patients without bilateral carotid artery stenosis (0%) (p < 0.001). Conclusions: It has not yet been clarified whether CMV is a primary trigger for atherosclerosis on the vascular wall, or whether it presents incidentally due to its affinity. When CMV (DNA) positivity was examined according to the presence of bilateral carotid artery stenosis in our study, CMV (DNA) positivity was found to be significantly higher in patients with bilateral carotid artery stenosis (63.16%).
Cellular and molecular players in the atherosclerotic plaque progression
Annals of the New York Academy of Sciences, 2012
Atherosclerosis initiation and progression is controlled by inflammatory molecular and cellular mediators. Cells of innate immunity, stimulated by various endogenous molecules that have undergone a transformation following an oxidative stress or nonenzymatic glycation processes, activate cells of the adaptive immunity, found at the borders of atheromas. In this way, an immune response against endogenous modified
Immunological aspects of atherosclerosis
Physiological research / Academia Scientiarum Bohemoslovaca, 2014
Atherosclerosis is a degenerative inflammatory disease of the vascular wall, which is characterized by the formation of atherosclerotic plaques that contain lipids, activated smooth muscle cells, immune cells, foam cells, a necrotic core and calcified sites. In atherosclerosis pathology, monocytes and macrophages play the most important role by accumulating redundant LDL particles in their oxidized form and producing proinflammatory cytokines. Atherosclerotic plaque macrophages reveal distinct phenotypes that are distinguished into M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages. Numerous environmental signals (cytokines, microbial cell molecules) that are received by macrophages drive their polarization, but it must be determined whether this classification reflects different macrophage subtypes or plasticity and phenotypic tissue changes, but the balance between subsets is crucial. M1 macrophages are dominant in symptomatic atherosclerotic plaques, while M2 macrophage...