Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to evaluate the influence of hyperlipemia on the specific cell defence reaction in type-II diabetes mellitus in humans, 20 diabetics were recruited in this study. They were divided into two groups on the basis of the absence or coexistence of abnormal serum lipid pattern. The lymphocyte and monocyte cells drawn from the type-II diabetic patients with abnormally elevated serum levels of cholesterol and triglycerides showed a decreased expression of major histocompatibility complex (MHC) class-II antigens and an impaired secretion of interleukin (IL-1). Values of MHC class-II antigen expression in diabetics without lipid metabolic alterations were not significantly different from those found in healthy subjects. In conclusion, abnormalities of lipid metabolism often found in type-II diabetes mellitus may play a key role in the impaired specific cell reaction toward infectious diseases of these patients.
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PMID:HLA class II antigens and interleukin-1 in patients affected by type-II diabetes mellitus and hyperlipemia. 850 2

Cardiac allograft vasculopathy (CAV) remains a troublesome long-term complication of heart transplantation. It is manifested by a unique and unusually accelerated form of coronary disease affecting both intramural and epicardial coronary arteries and veins.CAV is characterized by vascular injury induced by a variety of noxious stimuli, including the immune system response to the allograft, ischemia-reperfusion injury, viral infection, immunosuppressive drugs, and classic risk factors such as hyperlipidemia, insulin resistance, and hypertension. The obstructive vascular lesions are thought to progress through repetitive endothelial injury followed by repair response. The role of major histocompatibility complex donor-recipient differences in the pathogenesis of CAV has not yet been completely elucidated. Intracoronary ultrasound studies reveal a dual morphology with donor-transmitted or de novo focal, noncircumferential plaques in proximal segments and/or a diffuse, concentric pattern observed in distal segments. A lack of correlation between microvascular and epicardial vessel disease suggests discordant manifestations and progression of CAV. Apoptosis and loss of functional vascular remodeling have to be considered as important mediators of clinically relevant CAV. Strategies for blocking T-cell costimulation and expression of adhesion molecules may help prevent chronic rejection in clinical transplantation. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and antiproliferative drugs may slow progression of CAV by various effects. Methods to augment endogenous nitric oxide bioavailability as well as newer immunosuppressive regimens may be protective. Balloon angioplasty has a limited role in the treatment of focal lesions. Experiences with coronary stenting, coronary artery bypass grafting, and transmyocardial laser revascularization are limited. Retransplantation has a worse outcome than initial transplantation.
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PMID:Cardiac allograft vasculopathy: a review. 932

Calcineurin inhibitors such as cyclosporine (CsA) and tacrolimus (FK506) show similar efficacy to prevent rejection within the first year after organ transplantation. However, their use is limited by side effects, such as kidney damage, hypertension, new-onset diabetes, and hyperlipidemia. The consensus opinion suggests that compared with CsA, FK506 has fewer negative effects on blood pressure, serum lipids, and renal function. Nevertheless, FK506 use is associated with a higher incidence of posttransplantation diabetes mellitus. FTY720 is a new compound that has shown beneficial effects in animal models of rejection in transplantation, ischemia/reperfusion injury, autoimmune diseases, and tumor development. Our aim was to investigate whether FTY720 + tacrolimus association could provide additional immunosuppression without causing renal toxicity. FTY720 as a monotherapy or in association with FK506 was administered to C57BL/6 mice for 21 days to prevent skin graft rejection and to evaluate renal function and structure. Increased skin allograft survival in the FTY720 + FK506 group was associated with decreased cell numbers in the spleen, blood, and axillary lymph nodes. Changes in major histocompatibility complex (MHC) class II and intercellular adhesion molecule-1 (ICAM-1) expressions in splenocytes were also found in this group. The major effects already described for FK506 (diabetes) or FTY720 (lymphopenia) were observed after 21 days administration even when the drugs were associated. FTY720 associated with FK506 caused fewer changes in kidney structure, and blood glucose levels were lower than in FK506 monotherapy.
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PMID:Skin allograft survival and analysis of renal parameters after FTY720 + tacrolimus treatment in mice. 1845 36

Innate immune cells express danger-associated molecular pattern (DAMP) receptors, T-cell costimulation/coinhibition receptors, and major histocompatibility complex II (MHC-II). We have recently proposed that endothelial cells can serve as innate immune cells, but the molecular mechanisms involved still await discovery. Here, we investigated whether human aortic endothelial cells (HAECs) could be transdifferentiated into innate immune cells by exposing them to hyperlipidemia-up-regulated DAMP molecules, i.e. lysophospholipids. Performing RNA-seq analysis of lysophospholipid-treated HAECs, we found that lysophosphatidylcholine (LPC) and lysophosphatidylinositol (LPI) regulate largely distinct gene programs as revealed by principal component analysis. Metabolically, LPC up-regulated genes that are involved in cholesterol biosynthesis, presumably through sterol regulatory element-binding protein 2 (SREBP2). By contrast, LPI up-regulated gene transcripts critical for the metabolism of glucose, lipids, and amino acids. Of note, we found that LPC and LPI both induce adhesion molecules, cytokines, and chemokines, which are all classic markers of endothelial cell activation, in HAECs. Moreover, LPC and LPI shared the ability to transdifferentiate HAECs into innate immune cells, including induction of potent DAMP receptors, such as CD36 molecule, T-cell costimulation/coinhibition receptors, and MHC-II proteins. The induction of these innate-immunity signatures by lysophospholipids correlated with their ability to induce up-regulation of cytosolic calcium and mitochondrial reactive oxygen species. In conclusion, lysophospholipids such as LPC and LPI induce innate immune cell transdifferentiation in HAECs. The concept of prolonged endothelial activation, discovered here, is relevant for designing new strategies for managing cardiovascular diseases.
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PMID:Lysophospholipids induce innate immune transdifferentiation of endothelial cells, resulting in prolonged endothelial activation. 2976 17