Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HIV infection induces an early decrease of cholesterol and a late increase of triglycerides (TG) with a reduction of HDL. These changes are proportional with the lowering of CD4, which reflects the infection's severity. Both the increase of TG synthesis and the decrease of TG catabolism, in relation with a reduction of lipoprotein lipase activity, are responsible of these changes. Moreover, LDL catabolism is enhanced by macrophage scavenger receptors, due to a high proportion of small, dense LDL which are more easily oxidized. Many cytokines (interferon alpha, interleukins, TNF) play probably a pathogenic role in the dyslipidemia. Some HIV patients who received antiproteases may develop lipodystrophy with central obesity, insulino-resistance, glucose intolerance and sometimes diabetes (like in syndrome X). Other patients present a cushingoid, buffalo hump. This complication may be observed also with antiretroviral treatment other than antiproteases. The physiopathology of these findings could be in relation with structural homologies between antiproteases and some important proteins, involved in lipid and adipocyte metabolism. Cardiovascular risk linked to these perturbations is evident. The treatment is not different from the treatment for seronegative, hyperlipidemic patients: struggle against risk factors, diet advices, fibrates or statins. The antiproteases bring huge contribution to the prognosis of AIDS patients but the risk of cardiovascular complications could impair this therapeutic progress. So, it is essential to understand the pathogeny of these complications in order to discover new antiproteases, without these adverse side effects.
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PMID:[Lipids and AIDS]. 1074 83

Highly-active antiretroviral therapy (HAART) has lead to a dramatic decrease in the morbidity of patients infected with the human immunodeficiency virus (HIV). However, metabolic side effects, including lipodystrophy-associated (LD-associated) dyslipidemia, have been reported in patients treated with antiretroviral therapy. This study was designed to determine whether successful HAART was responsible for a dysregulation in the homeostasis of tumor necrosis factor-alpha (TNF-alpha), a cytokine involved in lipid metabolism. Cytokine production was assessed at the single cell level by flow cytometry after a short-term stimulation of peripheral blood T cells from HIV-infected (HIV(+)) patients who were followed during 18 months of HAART. A dramatic polarization to TNF-alpha synthesis of both CD4 and CD8 T cells was observed in all patients. Because it was previously shown that TNF-alpha synthesis by T cells was highly controlled by apoptosis, concomitant synthesis of TNF-alpha and priming for apoptosis were also analyzed. The accumulation of T cells primed for TNF-alpha synthesis is related to their escape from activation-induced apoptosis, partly due to the cosynthesis of interleukin-2 (IL-2) and TNF-alpha. Interestingly, we observed that LD is associated with a more dramatic TNF-alpha dysregulation, and positive correlations were found between the absolute number of TNF-alpha CD8 T-cell precursors and lipid parameters usually altered in LD including cholesterol, triglycerides, and the atherogenic ratio apolipoprotein B (apoB)/apoA1. Observations from the study indicate that HAART dysregulates homeostasis of TNF-alpha synthesis and suggest that this proinflammatory response induced by efficient antiretroviral therapy is a risk factor of LD development in HIV(+) patients.
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PMID:Alteration of tumor necrosis factor-alpha T-cell homeostasis following potent antiretroviral therapy: contribution to the development of human immunodeficiency virus-associated lipodystrophy syndrome. 1080 87

There have been increasing reports of acute coronary thrombotic events in patients with HIV. Although these clinical events have been attributed primarily to dyslipidemia associated with protease inhibitor therapy, autopsy studies in children with HIV suggest the presence of an underlying arteriopathy. This study demonstrates that the HIV envelope protein, gp120, activates human arterial smooth muscle cells to express tissue factor, the initiator of the coagulation cascade. The induction of tissue factor by gp120 is mediated by two biologically relevant coreceptors for HIV infection, CXCR4 and CCR5, and is also dependent on the presence of functional CD4. Induction of tissue factor by gp120 requires activation of mitogen-activating protein kinases, activation of protein kinase C, and generation of reactive oxygen species, signaling pathways that have protean effects on smooth muscle cell physiology. The activation of smooth muscle cells by gp120 may play an important role in the vascular, thrombotic, and inflammatory responses to HIV infection.
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PMID:HIV envelope gp120 activates human arterial smooth muscle cells. 1150 23

The aim of the study was the assessment of selected inflammatory markers in patients with stable and unstable angina pectoris, in comparison to patients with dyslipidemia without coronary artery disease. The study group included 61 patients (37-79 years old), divided into three subgroups: group I. 26 (43%) with unstable angina, group 2. 19 (26%) with stable angina, group III. 16 (26%) dyslipidemia without coronary artery disease. We measured serum levels of cytokines (IL-1B, IL-1Ra, IL-2, IL-6, TNF-alpha), immunoglobulins (IgG, IgE, IgM), fibrinogen. C-reactive protein and subclass of lymphocytes T CD4 and T CD8. In stable and unstable angina pectoris group we found lower percentage of T CD4, T CD8 and higher level of TNF-alpha. In unstable angina group the level of IL-1 beta was lower and the concentration of C-reactive protein, IgE was higher in comparison to group without coronary artery disease. Observed immunoregulatory disorders confirm immune mechanism in the origin of unstable angina pectoris.
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PMID:[Selected inflammatory markers in patients with acute coronary syndrome]. 1236 2

Atazanavir (formerly BMS-232632), an azapeptide protease inhibitor (PI), is a new human immunodeficiency virus (HIV) treatment that has recently received marketing approval from the FDA. It has a pharmacokinetic profile that supports once-daily dosing and has demonstrated a unique resistance profile and superior virologic potency compared with other antiretrovirals in vitro. In subjects with HIV, atazanavir (400 mg once daily) produced rapid and sustained improvements in viral load and CD4 counts in both antiretroviral-naive as well as previously treated patients when used in combination with dual nucleoside reverse transcriptase inhibitor (NRTI) treatment. In these studies atazanavir demonstrated comparable anti-HIV efficacy to nelfinavir (twice or three times daily), efavirenz and the combination of ritonavir and saquinavir. However, unlike these comparator agents, atazanavir did not adversely affect the plasma lipid profile, an advantage that sets it apart from other currently available PIs. Atazanavir was inferior to lopinavir/ritonavir in patients who previously failed an initial protease inhibitor containing regimen. Preliminary results in multiple PI-experienced patients indicate comparable efficacy to lopinavir/ritonavir in subjects receiving a boosted regimen of atazanavir plus ritonavir. In summary, atazanavir offers several therapeutic advantages, including a convenient once-daily dosing schedule, neutral lipid effects and a distinct resistance profile. These characteristics may ultimately help improve adherence, reduce the potential risk of long-term cardiovascular events associated with dyslipidemia, and increase the range of therapeutic options available for patients failing other antiretroviral regimens.
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PMID:Atazanavir: A novel once-daily protease inhibitor. 1564 3

Lipodystrophy syndrome comprises several conditions (lipoatrophy; lipohypertrophy; mixed syndrome, often associated with dyslipidemia; and insulin resistance). These conditions, though sometimes occurring together, may occur independently, suggesting a complex, multifactorial cause. To elucidate the relative contribution of risk factors of drug, disease, and host to fat redistribution, large epidemiologic studies using multivariate analysis were reviewed. In studies assessing lipoatrophy, the most common statistically significant risk factors were use of specific nucleoside analogues, increasing age, presence of markers of disease severity (CD4/HIV RNA), duration of therapy, and white race. In studies assessing lipohypertrophy, the most common statistically significant risk factors were duration of therapy, markers of disease severity, and protease inhibitor use. The pathogenesis of these disorders is complex, but recent hypotheses and evidence suggest that impairment to adipocyte differentiation, impairment of adipokine regulation, unopposed production of proinflammatory cytokines, dysregulation of 11-beta-hydroxysteroid dehydrogenase, and mitochondrial toxicity may play a role.
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PMID:Redefining lipodystrophy syndrome: risks and impact on clinical decision making. 1601 Jan 59

L-Carnitine (LC) and acetyl-L-carnitine (ALC) play major roles in cell energy and lipid metabolism. Supplementation with these nutrients, which are highly popular in USA, has been associated with favorable effects, including anti-oxidant action, neuro- and cardioprotection, immunomodulation, and cognitive enhancement. Patients with HIV infection and undergoing highly active antiretroviral therapy (HAART) often develop complications, such as polyneuropathy, skeletal myopathy, dyslipidemia and lipodystrophy, which have been linked to mitochondrial dysfunction. Moreover, these patients are often LC-deficient. Thus, they may benefit from LC and ALC supplementation. Indeed, oral, i.v., or i.m. administration of large doses of LC and/or ALC to HIV positive subjects untreated/treated with HAART was shown to: (1) increase the number of CD4 cells and reduce lymphocyte apoptosis; (2) improve symptoms of polyneuropathy; (3) prevent cardiovascular damage from wasting and diarrhea syndromes; (4) decrease serum levels of triglycerides and TNFalpha. No significant toxicities were associated with LC and ALC treatment. Although promising, most of these findings derive from small uncontrolled clinical trials. Further research is warranted to prove the efficacy and safety of LC and ALC supplementation in patients with complications of HIV infection and HAART.
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PMID:L-Carnitine and acetyl-L-carnitine in the treatment of complications associated with HIV infection and antiretroviral therapy. 1612 Mar 81

Metabolic abnormalities are common in patients with human immunodeficiency virus (HIV) infection and range from protein catabolism to lipodystrophy and dyslipidemia associated with the use of highly active antiretroviral therapy. One abnormality is increased resting energy expenditure, which even occurs in clinically stable HIV-infected patients. Increased resting energy expenditure may aggravate the tendency towards weight loss and wasting, which are independent predictors of mortality. Despite much investigation, the factors associated with altered resting energy expenditure remain unclear; viral load, CD4 cell count, use of antiretroviral drugs, body composition, hormones, and proinflammatory cytokines have been imputed. Mechanisms that could explain increased resting energy expenditure include the HIV accessory protein viral protein R, antiretroviral drugs that affect mitochondrial function, and futile cycling within adipocytes. Other components of energy expenditure are also important to overall energy balance and may also be affected. Identifying unifying mechanisms will be an important step to finding effective treatments for HIV-related alterations in energy expenditure and to reversing metabolic risks in patients with HIV infection.
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PMID:Dysregulated energy expenditure in HIV-infected patients: a mechanistic review. 1747 51

Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Various risk factors such as hypertension, dyslipidemia, and a proinflammatory and prothrombotic state contribute to atherogenesis in this high-risk population, but the pathophysiologic mechanisms leading to this characteristic pattern remain largely unexplored. Recent data suggest that the proinsulin cleavage product C-peptide could play a causal role in atherogenesis by promoting monocyte and CD4-positive lymphocyte recruitment in early arteriosclerotic lesions and by inducing the proliferation of vascular smooth muscle cells. The following review will summarize the effects of C-peptide in vascular cells and discuss the potential relevance of such C-peptide effects on atherogenesis in diabetic patients.
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PMID:C-peptide as a mediator of lesion development in early diabetes--a novel hypothesis. 1830 98

Human immunodeficiency virus (HIV) infection is associated with accelerated atherosclerosis and vasculopathy, although the mechanisms underlying these findings have not been determined. Hypotheses for these observations include: 1) an increase in the prevalence of established cardiac risk factors observed in HIV-infected individuals who are currently experiencing longer life expectancies; 2) the dyslipidemia reported with certain HIV anti-retroviral therapies; and/or 3) the proinflammatory effects of infiltrating HIV-infected monocytes/macrophages. An unexplored possibility is whether HIV itself can infect vascular smooth muscle cells (SMCs) and, by doing so, whether SMCs can accelerate vascular disease. Our studies demonstrate that human SMCs can be infected with HIV both in vivo and in vitro. The HIV protein p24 was detected by fluorescence confocal microscopy in SMCs from tissue sections of human atherosclerotic plaques obtained from HIV-infected individuals. Human SMCs could also be infected in vitro with HIV by a mechanism dependent on CD4, the chemokine receptors CXCR4 or CCR5, and endocytosis, resulting in a marked increase in SMC secretion of the chemokine CCL2/MCP-1, which has been previously shown to be a critical mediator of atherosclerosis. In addition, SMC proliferation appeared concentric to the vessel lumen, and minimal inflammation was detected, unlike typical atherosclerosis. Our data suggest that direct infection of human arterial SMCs by HIV represents a potential mechanism in a multifactorial paradigm to explain the exacerbated atherosclerosis and vasculopathy reported in individuals infected with HIV.
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PMID:Human immunodeficiency virus (HIV) infects human arterial smooth muscle cells in vivo and in vitro: implications for the pathogenesis of HIV-mediated vascular disease. 1831 May 3


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