Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atheroarteriosclerosis closely resembling that in humans was induced in normocholesterolemic and hypercholesterolemic chickens by infection with Marek's disease herpesvirus (MDV). Four comparably sized groups of chickens were used. Each group was initially fed a diet relatively poor in cholesterol. Group I and II were inoculated intratracheally at 2 days of age with MDV. At 15 weeks, one group of virus-infected chickens (Group II) and one group of uninfected controls (Group IV) were fed a 2% cholesterol supplement for an additional 15 weeks. Group I, infected, and III, uninfected, were continued on a cholesterol-poor diet. All groups were killed at 30 weeks. Striking grossly visible atherosclerotic lesions were seen in large coronary arteries, aortas, and major aortic branches of both Groups I and II but not in those of Groups III and IV. Microscopically, arterial changes in infected animals were characterized by occlusive fibromuscular intimal thickening, which formed fibrous caps overlying areas of atheromatous change. This change closely resembled chronic atherosclerosis in humans. These results may be important to our understanding of human arteriosclerosis, since there is widespread and persistent infection of human populations with as many as five herpesviruses.
 ...
PMID:Atheroarteriosclerosis induced by infection with a herpesvirus. 38 68

Our understanding of the pathogenesis and aetiology of atherosclerosis remains incomplete. An infection by herpesviruses is among the plausible hypotheses. In chicken, inoculation with Marek's disease virus provokes arterial lesions closely resembling atherosclerotic plaques. Experiments done on cultured arterial cells have shown that herpesviruses might enhance atherogenesis. Herpesviruses molecules (proteins, messenger ribonucleic acid, deoxyribonucleic acid) are commonly found in the human arterial wall. According to a recent study using gene amplification by the polymerase chain reaction, the complete cytomegalovirus genome can be detected in 90 p. 100 of the samples from atherosclerotic plaques and in 53 p. 100 of the samples from normal arterial wall. Cytomegalovirus infection appears to increase the risk and severity of atherosclerotic lesions which develop in heart grafts and compromise their survival. These data are not sufficient to prove that herpesviruses, especially cytomegalovirus, play a causal role in human atherosclerosis. The viral hypothesis, however, must be considered as serious and is certainly worth further investigations.
 ...
PMID:[Viruses and atherosclerosis]. 217 47

Japanese quail genetically selected on the basis of atherosclerosis susceptibility were tested for infection by Marek's disease herpesvirus (MDV). Viral DNA was detected in the atherosclerotic aortas of susceptible (SUS) quail by the technique of DNA hybridization. Southern blot analysis demonstrated that restriction mapping of aortic DNA was specific and different from that of MDV. Screening of quail embryos by dot-blot hybridization detected that MDV DNA existed in 100% of SUS quail tested. Resistant (RES) quail were a mixed population, with 16% of embryos resembling the SUS group. Functional MDV was not found by a number of methods including virus isolation, serological test, and exposure of sentinel chicks to SUS quail. These results suggest that the SUS quail possess a portion of the MDV genome in the germline, and the viral genes have been coselected by their susceptibility to cholesterol-induced atherosclerosis.
 ...
PMID:Discovery of noninfectious viral genes complementary to Marek's disease herpes virus in quail susceptible to cholesterol-induced atherosclerosis. 253 95

Genetically selected lines of Japanese quail, highly susceptible (SUS) and resistant (RES) to atherosclerosis, were used to study the possible involvement of Marek's disease herpes virus (MDV). An EcoRI gene library of MDV cloned in pBR328 was used to prepare the 32P-DNA probe in dot-blot and Southern blot hybridizations to detect the presence of MDV DNA sequence in the aorta, embryo and other tissue specimens. The viral DNA was found present in the aorta of SUS quail and it increased with the severity of the aortic lesion. For the DNA isolated from the atherosclerotic aorta, the endonuclease restriction map is specific but not identical to MDV genome. When screening the embryos of SUS and RES quail, it was found that all the SUS were positive with approximately 10 or more viral genome equivalents or virus copies per cell. The RES embryos were heterogeneous, 41% negative (less than 0.1 copy per cell), 43% intermediate (1-10 copies per cell) and 16% positive (10 or more copies per cell). The vaccination of SUS quail with the herpes virus of turkey vaccine did not prevent the disease. These results indicated that a part of MDV genome or another related herpes virus genome was integrated into the host DNA of SUS quail. The integrated viral gene or genes are believed to be important in atherogenesis, because they are genetically co-selected with the atherosclerosis-susceptibility.
Atherosclerosis 1987 Nov
PMID:Detection of specific DNA segments of Marek's disease herpes virus in Japanese quail susceptible to atherosclerosis. 282 27

Marek's disease herpesvirus (MDV) specific internal antigens were found in arterial segments of Single Comb White Leghorn, the Cornell strain, and of broiler chickens infected with virulent type 1 Mh-87 strain of MDV. Atherosclerosis was reproducibly induced in specific pathogen free (SPF) and in broiler chickens by infection with Mh-87 strain of MDV. Under these conditions a direct association was established between MDV infection and MDV-induced-atherosclerosis.
 ...
PMID:Marek's disease. XVII. Studies on virus induced-atherosclerosis. 283 Jul 14

Infection of normocholesterolemic, specific-pathogen-free chickens with Marek's disease herpesvirus (MDV) has been shown histologically to lead to chronic atherosclerosis like that in humans. The development of herpesvirus-induced atherosclerosis in vivo and the presence of specific Marek's antigen within aortic cells suggested that MDV infection may modify lipid metabolism and lead to significant lipid accumulation. Experiments reported herein were designed to determine the types and quantity of lipid present in aortas from MDV-infected and uninfected chickens between 2 and 8 months of age following infection and assess one possible mechanism of lipid accumulation by evaluating the effect of MDV infection on aortic cholesterol and cholesteryl ester (CE) metabolism. Chromatographic-fluorometric analyses indicated that at 4 and 8 months of age after MDV inoculation, MDV-infected animals had a significant (P less than 0.05) two-fold to threefold increase in total aortic lipid accumulation characterized by significant increases in cholesterol, CE, triacylglycerol, and phospholipid as compared with aortas from uninfected animals. At 8 months of age, similar increases in aortic lipid accumulation were observed in MDV-infected animals as compared with those animals vaccinated with turkey herpesvirus and later challenged with MDV. CE synthetic activity was increased significantly by 50% at 4 months of age in the MDV-infected group as compared with the uninfected group, which could explain the initial increase in CE accumulation. By 8 months of age, the authors also observed a twofold increase in CE synthetic activity and a 30% and 80% reduction in lysosomal and cytoplasmic CE hydrolytic activities, respectively, in aortas of MDV-infected chickens as compared to controls. Moreover, infection with MDV blocked the activation of cytoplasmic CE hydrolytic activity by dibutyryl cyclic AMP or exogenous cyclic AMP-dependent protein kinase. Taken together, these results suggest that lipid accretion in aortas of MDV-infected chickens results, in part, from alterations in cholesterol/CE metabolism during early stages of the disease. These findings support the hypothesis that human atherosclerosis may result from specific herpesvirus infection which can alter lipid metabolism and lead to lipid accretion.
 ...
PMID:Virus-induced atherosclerosis. Herpesvirus infection alters aortic cholesterol metabolism and accumulation. 293 87

We describe herein the effects of Marek's disease herpesvirus (MDV) on cholesterol and cholesteryl ester metabolism in cultured chicken arterial smooth muscle cells. Infection of arterial smooth muscle cells from specific pathogen-free chickens with MDV, but not a virus control, herpesvirus of turkeys led to a 7-10-fold increase in the accumulation of free and esterified cholesterol and a 2-fold increase in phospholipids. The cellular lipid changes observed in the MDV-infected arterial smooth muscle cells resulted, in part, from the following: decreased low-density lipoprotein-cholesteryl ester hydrolysis due to decreased lysosomal (acid) cholesteryl ester hydrolytic activity; increased de novo synthesis of cholesterol; decreased excretion of free cholesterol; and, both increased cholesteryl ester synthetic activity and decreased cytoplasmic (neutral) cholesteryl ester hydrolytic activity which resulted in increased incorporation of oleic acid into cholesteryl ester. Other changes noted in the MDV-infected cells as compared to uninfected cells included a 2-fold increase in both total protein synthesis and lysosomal and microsomal marker enzyme activities. These alterations in lipid and protein metabolism in MDV-infected arterial smooth muscle cells may explain in part our in vivo findings that herpesvirus (MDV) infection of specific pathogen-free chickens fed a normocholesterolemic diet will induce arterial thickening and lipid accumulation resembling human atherosclerosis.
 ...
PMID:Altered cholesteryl ester cycle is associated with lipid accumulation in herpesvirus-infected arterial smooth muscle cells. 399 16

In our previous experiments, atherosclerosis similar to that in humans was reproducibly induced in both normocholesterolemic and hypercholesterolemic specific-pathogen-free (SPF) chickens by infection with Marek's disease herpesvirus (MDV). In contrast, uninfected chickens fed either relatively cholesterol-poor or cholesterol-supplemented diets did not develop this arterial disease. In experiments reported here, the hypothesis that infection of arterial smooth muscle cells (SMCs) with MDV would enhance lipid accumulation in these cells was tested. The number of MDV-infected SMCs with lipid stained with oil red O was assessed, and the lipid content of these cells was quantitated chemically by chromatographic and fluorometric analyses. These data were compared to those of uninfected control cells and, in the case of chemical analyses, were also compared to SMCs infected with a second avian herpesvirus, turkey herpesvirus (HVT). Results indicate the following: 1) The percentage of MDV-infected SMCs containing stainable lipid was significantly greater than the percentage of uninfected SMCs; 2) Increased total lipid accumulation was observed in MDV-infected SMC, particularly cholesterol (CH) and cholesteryl esters (CEs), as compared with uninfected or HVT-infected cells; 3) The types of CEs and nonesterified fatty acids (NEFA) accumulating in MDV-infected cells (particularly saturated types of CEs and NEFAs) were significantly different than those in uninfected or HVT-infected SMCs. These qualitative and quantitative differences in lipid content between infected and uninfected SMCs suggest that infection with MDV results in altered intracellular lipid metabolism. Results support the hypothesis that lipid accumulation in arteries of normocholesterolemic chickens may result from MDV infection acting at the cellular level to induce lipid accumulation that resembles that in human atheroarteriosclerosis.
 ...
PMID:Herpesvirus infection enhances cholesterol and cholesteryl ester accumulation in cultured arterial smooth muscle cells. 627 Oct 18

A retrospective study was performed to evaluate the potential of a mammalian oncogenic virus, Herpesvirus saimiri, to cause atherosclerosis in owl monkeys (Aotus trivirgatus). This was undertaken since an avian oncogenic herpesvirus, Marek's disease virus, does so in chickens. Data from earlier studies were reviewed and 3 groups of animals were selected. These included 23 animals infected with herpesvirus that died an average of 156 days later with malignant lymphoma; 11 infected an average of 207 days before being killed without lymphoma; and 21 uninfected control animals that died from a variety of diseases. Aortas and hearts from all animals were recovered from storage in formalin and examined for histopathological evidence of atherosclerosis in aortas and coronary arteries. Mild to moderate atherosclerosis characterized by intimal proliferation and the presence of fat droplets was present in 60% of the monkeys and did not differ in occurrence between the groups. Mean intimal thickness did not vary significantly between groups either. A case of naturally-occurring severe atherosclerosis is also reported here. Thus, although this species is susceptible to atherosclerosis, neither the occurrence nor severity of that disease is affected by infection with an oncogenic virus within the time periods studied here.
Atherosclerosis 1983 Feb
PMID:Failure of Herpesvirus saimiri to enhance atherogenesis in owl monkeys (Aotus trivirgatus). 630 14

Repeated experiments have established that infection with Marek's disease herpesvirus (MDV) leads to atherosclerosis in specific pathogen free (SPF) normocholesterolemic chickens. Neither normocholesterolemic nor hypercholesterolemic uninfected SPF chickens develop this disease. The MDV-induced arterial disease is remarkably similar to chronic human atherosclerosis. Cholesterol and saturated cholesteryl esters accumulated in cultured arterial smooth muscle cells (SMC) infected with MDV. Similar preliminary observations were made in vivo. These findings suggest that MDV-induced alteration of SMC lipid metabolism is of major importance in the pathogenesis of MDV-induced atherosclerosis. In addition, immunization with turkey herpesvirus, used commercially to prevent MDV-induced tumors in chickens, also protected against MDV-induced atherosclerosis. This animal model has introduced important new dimensions and tools in atherosclerosis research: a defined etiologic agent (MDV) that causes atherosclerosis in a defined animal of known genetic susceptibility to the etiologic agent. With these tools, important mechanisms in the pathogenesis of atherosclerosis may be established in a relatively short period of time. Further, this animal model should be considered important in other models of atherosclerosis research because herpesvirus infections are ubiquitous in these animals. Finally, because humans are widely and persistently infected with up to five herpesviruses, these studies may lead to the understanding and eventual control of human atherosclerosis.
 ...
PMID:Herpesvirus-induced atherosclerosis in chickens. 684 Feb 98


1 2 Next >>