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)

The treatment of HIV-positive patients with protease inhibitors has been suggested to increase their risk of atherosclerosis. The cause of this accelerated atherogenesis is unknown, but on the basis of previous studies we postulated that it could be linked to the presence of human herpesvirus-8. A retrospective analysis of post-mortem reports showed a strong correlation between Kaposi's sarcoma and the presence of atheroma. This hypothesis merits further investigation.
AIDS 2001 Sep 28
PMID:Association between Kaposi's sarcoma and atherosclerosis: implications for gammaherpesviruses and vascular disease. 1157 62

We report the case of a 40-year-old HIV-positive man, undergoing three-drug antiretroviral therapy for 2 years that included a protease inhibitor (ritonavir). The patient was admitted to our Coronary Care Unit with an acute anterior myocardial infarction. He smoked 20 cigarettes/day and had a family history of hypertension. At the time of hospitalization, triglyceride levels were found to be high (290 mg/dl). Metabolic alterations associated with the prolonged use of protease inhibitors, such as insulin resistance, dyslipidemia and lipodystrophy, have recently been described. This side effect may lead to premature coronary artery disease. Therefore it is mandatory to be aware that treatment with protease inhibitors in HIV-positive patients, despite survival prolongation and lowering of AIDS complications, may accelerate atherosclerosis and precipitate acute coronary events, especially in patients with pre-existing cardiovascular risk factors.
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PMID:[Acute myocardial infarct in HIV-positive patients in treatment with protease inhibitors]. 1177 17

Nuclear factor kappa B (NF-kappaB) is a family of inducible transcription factors found virtually ubiquitously in all cells. Since its discovery by Sen and Baltimore in 1986, much has been discovered about its mechanisms of activation, its target genes, and its function in a variety of human diseases including those related to inflammation, asthma, atherosclerosis, AIDS, septic shock, arthritis, and cancer. Due to its role in a wide variety of diseases, NF-kappaB has become one of the major targets for drug development. Here, we review our current knowledge of NF-kappaB, the possible mechanisms of its activation, its potential role in cancer, and various strategies being employed to target the NF-kappaB signaling pathway for cancer drug development.
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PMID:Nuclear transcription factor-kappaB as a target for cancer drug development. 1204 Apr 37

Free radical attack upon DNA generates a multiplicity of DNA damage, including modified bases. Some of these modifications have considerable potential to damage the integrity of the genome. This article reviews recent data that suggest the involvement of oxidative DNA damage in carcinogenesis, atherosclerosis, and acquired immunodeficiency syndrome (AIDS). There is evidence that oxidative DNA damage may play a causative role in atherosclerosis. Oxidative DNA damage may lead to apoptotic cell death of patients infected with human immunodeficiency virus (HIV) and may influence the progression of AIDS. While many details regarding the role of reactive oxygen species-induced DNA damage in the etiology of complex multifactorial diseases like cancer are yet to be discovered, evidence suggests that oxidants act at several stages in the malignant transformation of cells. However, the quantitative relationship between the measured DNA damage and the development of cancer is still lacking.
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PMID:Oxidative DNA damage: assessment of the role in carcinogenesis, atherosclerosis, and acquired immunodeficiency syndrome. 1210 15

Controlled trials suggest that acyclovir/valacyclovir can provide significant clinical benefits when used for prophylaxis in the immunocompromised host. These findings implicate herpesvirus(es) in the pathogenesis of complex medical conditions, including graft rejection and death. However, it is not known which of the 8 herpesviruses are important under particular circumstances. Prime candidates for triggering adverse outcomes are cytomegalovirus (CMV) in solid organ transplant recipients (causing rejection), CMV and human herpesvirus type 6 (HHV-6) in bone marrow transplant patients (causing marrow suppression), and herpes simplex virus, HHV-6, and CMV in AIDS patients (accelerating the rate of human immunodeficiency virus disease progression and death). Other diseases that may have a herpesvirus component or trigger susceptible antiviral agents include atherosclerosis and multiple sclerosis. In the future, clinicians should be alert to novel findings of randomized trials that may provide insight into the pathogenesis of these diseases and the contributions made by clinically silent herpesvirus infections.
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PMID:Tomorrow's challenges for herpesvirus management: potential applications of valacyclovir. 1235 98

The use of Human Immunodeficiency Virus (HIV) protease inhibitors as part of the Highly Active Antiretroviral Therapy (HAART) is associated with atherogenic dyslipoproteinemia, insulin resistance, hypertension and endothelial dysfunction, all of which contribute to premature coronary heart disease. These abnormalities appear to be associated with an increase in cardiovascular events in HIV-infected patients. Beneficial metabolic effects of anti-diabetic agents used in HIV-infected patients have been reported. The thiazolidinediones (TZDs), a new group of antidiabetic drugs, may modulate the proliferative and inflammatory cascades involved in atherosclerosis. Thus, an increasing totality of evidence suggests that TZDs may represent a unique and powerful research tool to find a common denominator underlying the pathophysiology and treatment of the metabolic cardiovascular risk factors associated with HIV infection.
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PMID:Thiazolidinediones could improve endothelial dysfunction and risk of premature coronary heart disease in HIV-infected patients. 1249 Sep 65

We recently identified two stably expressed cell surface markers, IL-18R and ST2L, which are selectively expressed on T1/NK1 and T2/NK2 cells, respectively. Here we use these molecules in direct ex vivo analysis of PBMCs from patients with AIDS, psoriasis (PS) atherosclerosis and to show the importance of these markers as determinants of the functional dichotomy of lymphocyte subsets, in particular NKT. In a cohort of 22 HIV patients made up of a mixture of long term non-progressors, seroconvertors, progressors and asymptomatics, we found a clear NKT1 to NKT2 shift (P=0.001) in the HIV-infected individuals. We also show a predominance of NKT2 cells over NKT1 cells in the PBMCs of patients with mild to moderate PS (N=13, P=0.005) but not in atopic dermatitis or healthy controls. However, in patients (N=6) requiring surgery for aneurysm, a predominance of Type 1 (IL-18R(+)) NKT lymphocytes over NKT2 was detected among infiltrating lymphocytes isolated from atherosclerotic plaques. Our data therefore demonstrate that ST2L and IL-18R could serve as important determinants of the immune status of human diseases.
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PMID:NKT cell subsets in infection and inflammation. 1252 23

The endothelium participates in haemostasis, inflammation, blood pressure regulation and other physiological systems. Consequently, endothelial dysfunction has been related to hypertension, thrombosis and atherosclerosis. Both von Willebrand factor (vWF) and tissue-type plasminogen activator (t-PA) are synthesized by the endothelium and their plasma levels increased during endothelium activation or injury. So far, they are well-known markers of endothelial cell function. Many circumstances activate or damage the endothelium, such as viruses, bacterium and inflammation. Circulating vWF and t-PA were studied in 92 unselected human immunodeficiency virus-1 (HIV-1)-infected patients [27 patients with and 65 patients without acquired immunodeficiency syndrome (AIDS)] and correlated with plasma levels of pro-inflammatory cytokines (tumour necrosis factor-alpha, interleukin-6), viral load, CD4 T-cell count and infectious status. HIV-1-infected patients had significantly higher plasma levels of vWF (152 versus 90%), tumour necrosis factor-alpha (31.3 versus 9.0 pg/ml) and interleukin-6 (3.5 versus 1.9 pg/ml) but not t-PA (5.9 versus 4.2 ng/ml) than the control group. These two endothelial markers correlated significantly with viral load and interleukin-6 levels in HIV-1-infected patients. The highest levels of vWF and t-PA were found in patients with AIDS. In conclusion, endothelial cell perturbation is present in HIV infection and may be a consequence of different mechanisms such as viral load, cytokines and advanced diseases.
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PMID:Viral load and disease progression as responsible for endothelial activation and/or injury in human immunodeficiency virus-1-infected patients. 1254 23

Recent evidence suggests that as a group protease inhibitors (PIs) may accelerate certain factors associated with atherosclerosis. The objective of this study was to evaluate the effect of individual PIs (indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir) on certain factors associated with atherosclerosis. Persons who took saquinavir and/or ritonavir were compared with those on other PIs. Between May 2000 and July 2001, the lipid profiles, C-reactive protein (CRP) levels, coronary artery calcium (CAC) scores, and blood cell morphologic parameters were measured in 98 black adult participants aged 25 to 45 years with HIV-1 infection in Baltimore, Maryland. Among these 98, there were 55 (56.1%) taking PIs. Students' t-test and chi2 test were used to detect the between-group differences. Study participants in both the PI and non-PI groups were similar in age, sex, body mass index, blood pressure, red and white blood cell counts, time since HIV diagnosis, and duration on anti-retroviral therapy. Compared with those who took non-PI regimens, those who took indinavir, nelfinavir, or saquinavir had significantly higher levels of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Those taking any PI had significantly higher total cholesterol and low-density lipoprotein. Those taking nelfinavir, ritonavir, or saquinavir were more likely to have a higher CAC score (>5) than those on non-PI regimens. There were no differences in the lipid profiles, MCV, MCH, CRP, and CAC between those taking saquinavir and/or ritonavir and those taking other PIs. Overall, the changes noted might lead to anticipation of clinical changes linked to accelerated atherosclerosis in patients on PIs.
AIDS Patient Care STDS 2003 May
PMID:Factors associated with accelerated atherosclerosis in HIV-1-infected persons treated with protease inhibitors. 1281 15

Whether the atherogenic metabolic side effects of highly active antiretroviral therapy (HAART) (lipid disorders and glucose intolerance/diabetes) will translate, in the long term, into an increased incidence of cardiovascular events that would offset the survival benefits of this type of therapy is a matter of intense concern. This concern has been substantiated by a series of case reports of HIV-infected patients who had experienced unexplained cardiovascular disease. However, in the absence of prospective, large cohort studies, the answer to this question at present remains elusive. Indirect evidence, from retrospective cohort analyses and non-invasive imaging of peripheral arteries, indicates that HIV-infected persons are at higher risk for atherosclerosis than HIV-negative individuals. However, this risk does not appear to be attributable to HAART. Pending the availability of further data, a global assessment of the risk for heart disease should be performed in all HAART-treated HIV-infected patients, taking into account age and the presence of major risk factors. There is so far no evidence, from a cardiovascular standpoint, to limit administration of HAART. However, interventions on modifiable risk factors, including smoking cessation, are strongly recommended, particularly in high-risk patients.
AIDS 2003 Apr
PMID:Atherosclerosis and HIV in the highly active antiretroviral therapy era: towards an epidemic of cardiovascular disease? 1287 May 32


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