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

Vascular smooth muscle cell (SMC) proliferation in response to injury is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis after balloon angioplasty. The retinoblastoma gene product (Rb) is present in the unphosphorylated and active form in quiescent primary arterial SMCs, but is rapidly inactivated by phosphorylation in response to growth factor stimulation in vitro. A replication-defective adenovirus encoding a nonphosphorylatable, constitutively active form of Rb was constructed. Infection of cultured primary rat aortic SMCs with this virus inhibited growth factor-stimulated cell proliferation in vitro. Localized arterial infection with the virus at the time of balloon angioplasty significantly reduced SMC proliferation and neointima formation in both the rat carotid and porcine femoral artery models of restenosis. These results demonstrate the role of Rb in regulating vascular SMC proliferation and suggest a gene therapy approach for vascular proliferative disorders associated with arterial injury.
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PMID:Cytostatic gene therapy for vascular proliferative disorders with a constitutively active form of the retinoblastoma gene product. 782 50

Infection with a human herpes virus, particularly cytomegalovirus (CMV), has been hypothesized to be a cofactor in the development of atherosclerosis in humans. We investigated the association of prior CMV infection with the presence of atherosclerosis in the coronary arteries of the native heart of 314 individuals undergoing heart transplantation. Age, male gender, race, tobacco use, and previous general and cardiac surgery were also studied as covariables. Factors associated with the presence of coronary atherosclerosis by univariate analysis were age greater than the median of 48 years (odds ratio [OR] = 5.9, 95% confidence intervals [CI] 3.0-11.6; P < 0.0001), tobacco use (OR = 3.8, 95% CI 2.1-7.0; P < 0.005), CMV seropositivity (OR = 3.1, 95% CI 1.8-5.5; P < 0.001), and male gender (OR = 3.0, 95% CI 1.6-5.4; P < 0.0005). When patients were divided into quartiles based on age, coronary atherosclerosis was shown to be associated with CMV seropositive status only in the youngest quartile of patients (OR = 3.6, 95% CI 1.4-8.9; P < 0.01) but not in the older three quartiles of patients (OR = 0.9, 95% CI = 0.3-2.4; P > 0.5). In multiple logistic regression analyses, CMV seropositivity was not a significant independent variable in the whole group of patients (P = 0.13) but remained a significant variable in the youngest quartile of patients (P = 0.01). However, 43% of these younger patients and 29% of all patients with coronary atherosclerosis were seronegative for CMV.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Investigation of cytomegalovirus infection as a risk factor for coronary atherosclerosis in the explanted hearts of patients undergoing heart transplantation. 785 75

Infection is a devastating complication of synthetic aortic graft surgery. Patients with significant occlusive atherosclerosis of the internal iliac arteries undergoing aortic graft removal for graft infection may be at risk of pelvic and midbody necrosis. An unusual and fatal complication of this nature associated with the management of synthetic aortic graft infection has been encountered in two patients treated by extra-anatomic revascularization and staged removal of the infected aortic prosthesis. The hallmark of their presentation was pelvic and midbody necrosis in the presence of excellent distal perfusion with palpable pulses. Marginal pelvic circulation was therefore compromised further by graft removal and absence of retrograde pelvic perfusion. The finding of focal ischemic changes in the pelvic area of a patient with increasing serum creatinine phosphokinase activity, leukocytosis, myoglobinuria and paraplegia following infected aortic graft removal signals a grave and fatal prognosis.
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PMID:Pelvic necrosis: a complication of infected aortic graft excision. 807 36

The authors found a significant reduction of the suppressor function in carriers of the Australian antigen. This may contribute to a formation of immune complexes. Infection of rabbits with Herpes simplex virus resulted in an essentially enhanced development of experimental atherosclerosis against the background of a reduction of the suppressor function. These findings give evidence of the importance of viral infection in the development of atherosclerosis due to an inhibition of the suppressor function of T lymphocytes.
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PMID:[Influence of viral infections in the pathogenesis of atherosclerosis]. 813 Jan 63

Systemic infections may thicken the intima of coronary arteries and modify the serum lipid profile. Infants and children are particularly susceptible to such intimal thickening, the signs of which are more pronounced in infants who have evidence of infection at death. The topography of the thickenings, their greater size in males, and in families with a history of coronary heart disease favours the idea that the thickenings are pre-atherosclerotic. Infections modify the serum lipid pattern: serum high density lipoprotein (HDL) cholesterol concentration decreases and stays low during convalescence. Thus repeated infections might prove to be a risk factor for atherosclerosis via their effect on HDL concentration.
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PMID:Altered serum lipid profile after systemic infection in children: risk factor for CHD? 813 93

Previous studies of age-related susceptibility to viral infection have focused largely on the effects of aging on the immune response. Little attention has been given to age-related changes in the infectivity of target cells. We show here a fourfold greater plating efficiency of herpes simplex virus type 1 (HSV-1) for cultured vascular smooth muscle cells derived from adult rats compared with cells from genetically identical pup rats. The difference in plating efficiency appeared to be due to differences in initial attachment of the virion to the cell surface. There were no differences in the rate of viral entry or the efficiency of viral replication at high multiplicities of infection and no resistant "subpopulation" of pup cells. The pup cells did not release a soluble inhibitor of infection. Infection in both cell types was inhibited similarly by basic fibroblast growth factor (bFGF). Although adult cells exhibited a more vigorous mitogenic response to bFGF than did pup cells, binding studies did not demonstrate significant differences in the binding of bFGF to the cell surface, suggesting that differential expression of high-affinity FGF receptors could not be correlated with the difference in infectivity. We speculate that differences in the distribution of heparan sulfate in the cell surface, which serves as the initial attachment site for HSV-1, may explain the observed differences in plating efficiency. Since age is a risk factor for the development of atherosclerosis, these results have potential implications for susceptibility of the vasculature to herpesviral infections as a function of the development of the vessel wall.
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PMID:Developmentally regulated herpesvirus plaque formation in arterial smooth muscle cells. 838 74

Abnormal migration and proliferation of arterial smooth muscle cells may be a central event in inflammatory proliferative arterial diseases such as atherosclerosis and restenosis after angioplasty. The proto-oncogene c-H-ras is considered to be a key transducer in various growth-signaling events. We constructed an adenoviral vector (AdexCAHRasY57) expressing a potent dominant-negative mutated form of c-H-ras in which tyrosine replaces aspartic acid at residue 57. Infection of smooth muscle cells with AdexCAHRasY57 produced a large quantity of H-ras-p21, completely inhibited serum-stimulated activation of mitogen-activated protein kinase, and abolished the DNA synthesis in response to serum mitogens. However, a surge of intracellular Ca2+ concentration in response to platelet-derived growth factor was not affected, suggesting that some cellular functions were preserved. When we applied AdexCAHRasY57 into balloon-injured rat carotid arteries from inside the lumen, neointimal formation was significantly reduced (neointima/media ratio: 0.28) compared with that (1.50) in arteries treated with either injury alone or injury and infection with a control adenovirus, AdexCALacZ, expressing bacterial beta-galactosidase. Our results suggest that adenovirus-mediated arterial transfer of dominant-negative H-ras may be a practical form of effective molecular intervention for proliferative arterial diseases.
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PMID:Adenovirus-mediated transfer of a dominant-negative H-ras suppresses neointimal formation in balloon-injured arteries in vivo. 915 53

To investigate the possibility of adenovirus-mediated gene transfer in the treatment of vascular occlusive diseases, we constructed a replication-deficient recombinant adenovirus vector coding for human basic fibroblast growth factor (bFGF) and examined its effect on the proliferation and differentiation of vascular endothelial cells in vitro. Human umbilical vein endothelial cells (HUVECs) were successfully infected with high efficiency and expressed 18 kD protein which is immunoreactive to anti-bFGF monoclonal antibody. This protein was accumulated mainly in the nuclei of the cells, but was also detected in the culture medium although the complimentary DNA (cDNA) did not contain the classical secreting signal sequence. The proliferation assay of HUVECs infected with bFGF-expressing adenovirus revealed a significant increase in cell number over control. Infection with this virus also enhanced tubular formation of HUVECs on reconstituted basement membrane. Neovascularization and the formation of collateral vessels play important roles in minimizing tissue damage in ischemic disorders. These results imply that the use of bFGF-expressing recombinant adenovirus may be a suitable in vivo gene therapy for ischemic diseases.
Atherosclerosis 1997 Jul 25
PMID:Adenovirus-mediated gene transfer of basic fibroblast growth factor induces in vitro angiogenesis. 924 65

An increasing body of evidence has linked infections to atherosclerosis and thrombosis. Herpesviruses cause atherosclerosis in experimental animals. Herpesviruses can also be detected in atherosclerotic lesions in humans. Cytomegalovirus may play a role in arteriosclerosis in transplanted hearts, and this virus, together with tumor suppressor protein p53, can be found in restenosis lesions following angioplasty. Chlamydia pneumoniae and dental infections are associated with coronary heart disease in cross-sectional and longitudinal studies, and preceding respiratory infections are associated with ischemic stroke. Infections may favor formation of atherosclerosis and thrombosis by elevation of blood levels of fibrinogen, leukocytes, clotting factor, and cytokines and by alteration of the metabolism and functions of endothelial cells and monocyte macrophages. Low-grade infections may also be one of the causes of the inflammatory reaction observed in atherosclerotic lesions and acute ischemic symptoms, reflected in elevated levels of C-reactive protein. These observations warrant further studies in this field.
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PMID:Role of infection as a risk factor for atherosclerosis, myocardial infarction, and stroke. 952 51

Infections are an increasing problem in the elderly population, because of the often atypical presentation and the more frequent occurrence of complications, which lead to increased morbidity and mortality. The increased prevalence of infections in the elderly is due to a number of factors: increased exposure to micro-organisms (especially in nursing homes); degeneration of various organs (atherosclerosis, pulmonary emphysema, diverticulosis, prolapse); decreased immune response; concomitant diseases (e.g. diabetes mellitus) and (or) use of medication. There is often a delay in the diagnosis because the presentation of infection in the elderly is frequently atypical and symptoms are attributed to old age, rather than to infection. Treatment may be hampered by increased resistance of micro-organisms, interaction with other drugs and toxicity problems.
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PMID:[Infections in elderly patients]. 955 Jul 96


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