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)

The accelerated formation of advanced glycation/lipoxidation end products (AGEs/ALEs) has been implicated in the pathogenesis of various diabetic complications. Several natural and synthetic compounds have been proposed and advanced as inhibitors of AGE/ALE formation. We examined the effects of two new AGE/ALE inhibitors, LR-9 and LR-74, on the prevention of early renal disease and dyslipidemia in streptozotocin (STZ)-induced diabetic rats. Diabetic rats were treated with either LR-9 or LR-74 for 32 weeks. Progression of renal disease was evaluated by measurements of urinary albumin and plasma creatinine concentrations. AGE-induced chemical modification of the tail tendon collagen and levels of Nepsilon-(carboxymethyl)- and (carboxyethyl)- lysines (CML and CEL) in skin collagen were measured. AGE/ALE levels in kidneys were determined by immunohistochemistry. Plasma lipids and their lipid hydroperoxide concentrations were also determined. Treatment of either LR-9 or LR-74 significantly inhibited the increase in albuminuria, plasma creatinine, hyperlipidemia, and plasma lipid peroxidation in diabetic rats without any effects on hyperglycemia. Both compounds also reduced CML-AGE accumulation in kidney glomeruli and tubules, AGE-linked fluorescence and cross-linking of tail collagen, and levels of CML and CEL in skin collagen. These results suggest that both LR compounds can inhibit the progression of renal disease and also prevent dyslipidemia in experimental diabetes. These compounds may have an additional beneficial effect as an antioxidant against lipid peroxidation, and thus may provide alternative therapeutic options for the treatment of various diabetic macrovascular complications.
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PMID:Renoprotective and lipid-lowering effects of LR compounds, novel advanced glycation end product inhibitors, in streptozotocin-induced diabetic rats. 1603 4

Studies show that systemic diseases such as diabetes, hyperthyroidism, osteoporosis, and dyslipidemia may influence periodontal inflammation. However, few studies relate the influence of arterial hypertension on periodontitis. The present study was undertaken to assess the severity of the experimental ligature-induced periodontitis in an experimental model of genetic arterial hypertension. The experimental periodontitis model was induced in 6 spontaneously hypertensive rats (SHR) and 6 Wistar normotensive rats (NT) by cotton ligature, which was placed subgingivaly around the neck of the first left inferior molar tooth. In the same animal, the first right molar tooth was sham-ligated and used as a control. After 7 days, the mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious animals. As expected, MAP was significantly higher in SHR (151 +/- 6 mmHg) than in NT (105 +/- 3 mmHg), without significant differences in HR. The histopathologic examination of the periodontal structure showed alveolar integrity and lack of neutrophils and osteoclasts in the control side of both SHR and NT. In contrast, examination of the ligated side in all animals showed collagen degradation in the alveolar process from a moderate (50%) to severe (50%) level in SHR and mild in NT (100%). These data show that experimental periodontitis, characterized by the spreading of the inflammatory process from the gingiva deep into periodontium tissues, is greatly exacerbated in SHR.
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PMID:Experimental-induced periodontitis is exacerbated in spontaneously hypertensive rats. 1608 44

Dyslipidemia often accompanies and accelerates renal disease, partly by promoting fibrosis. However, the mechanisms mediating this effect are unclear. We hypothesized that hypercholesterolemia modulates several interlinked pathways that promote deposition and blunt degradation of extracellular matrix, and that these could be manipulated by reversal of hypercholesterolemia. Fourteen pigs were fed a 16-week 2% high-cholesterol diet (HC-HC; n=7) or normal diet (n=7), whereas in 7 others, a 10-week HC was followed by a 6-week normal diet (HC-N). Renal endothelial function was assessed in vivo with electron-beam computed tomography, and renal tissue was then studied ex vivo using Western blot, real-time quantitative polymerase chain reaction, gelatin zymography, and immunostaining. HC-HC kidneys showed endothelial dysfunction, accompanied by increased intrarenal oxidative stress, inflammation, activation of the endothelin and transforming-growth factor-beta systems, and decreased matrix metalloproteinase expression and activity. Accordingly, HC-HC kidneys showed increased collagen IV expression and fibrosis. A lipid-lowering dietary intervention reversed most of these changes. In conclusion, this study indicates that renal fibrosis in early atherosclerosis is a result of a simultaneous increase in extracellular matrix deposition and blunted matrix metalloproteinase-mediated degradation, overall promoting perivascular and tubulointerstitial fibrosis. Notably, many of these pathways may be reversible in hypercholesterolemia, and crucial targets could potentially be identified for early interventions to preserve the kidney.
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PMID:Pathways of renal fibrosis and modulation of matrix turnover in experimental hypercholesterolemia. 1617 24

The study was designed to assess blood platelet sensitivity to acetylsalicylic acid and its associations with dyslipidaemia and inflammation in coronary artery disease patients. Platelet non-responsiveness to aspirin is associated with an increased risk of serious cardiovascular events. Several environmental and hereditary factors are reportedly involved in sub-optimal acetylsalicylic acid response. Forty-five coronary artery disease patients and 45 non-coronary artery disease controls received acetylsalicylic acid at a daily dose of 75-150 mg. Controls were examined twice: on the day of entering the study and 10 days later. Urinary 11-dehydrothromboxane B2 was assessed as the marker of platelet thromboxane generation. Aggregation was studied in platelet-rich plasma using turbidimetric aggregometry with collagen and arachidonic acid. Fifty to seventy percent of coronary artery disease patients showed an extent of collagen-induced aggregation above the upper quartile of the reference range compared with 8-15% in controls (P<0.003). For arachidonic acid-activated aggregation these proportions were 45-50% in coronary artery disease versus 7% in controls (P<0.007). In coronary artery disease patients, the acetylsalicylic acid-mediated platelet inhibition positively correlated with increased triglycerides (in arachidonic acid-stimulated platelets, r=0.30, P=0.0018), total cholesterol (r=0.33, P<0.0001 in coll and arachidonic acid-activated platelets) and elevated serum C-reactive protein (CRP) (r=0.27, P=0.0024). In coronary artery disease patients urine 11-dehydrothromboxane B2 concentrations were significantly increased compared to controls after 10 day acetylsalicylic acid intake (563; 313-728 pg/mg creatinine versus 321; 246-488 pg/mg creatinine, P=0.04). The incidence of suboptimal acetylsalicylic acid response incidence was more common in patients with coronary artery disease. Acetylsalicylic acid inhibition of blood platelet reactivity and thromboxane generation was less effective in these patients. Dyslipidaemia and chronic inflammatory states may promote suboptimal acetylsalicylic acid response in coronary artery disease patients.
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PMID:Reduced blood platelet sensitivity to aspirin in coronary artery disease: are dyslipidaemia and inflammatory states possible factors predisposing to sub-optimal platelet response to aspirin? 1663 10

Insulin resistance and the consequent metabolic disorders are associated with a state of platelet hyperactivity. Oxidative stress is responsible for the persistent platelet activation. We sought to study the inhibitory effect of cardiotonic pills, an oral herbal component, on platelet function in a dog model with insulin resistance induced by high-fat feeding. We fed 18 dogs with a high-fat diet and six dogs with normal chow as control for 6 months. Then, six dogs were fed with a high-fat diet and received additional aspirin (250 mg/day), and another six dogs received additional cardiotonic pills (1,000 mg/day) for 4 months. Time-course changes in metabolic parameters and platelet function were detected. After high-fat feeding for 6 months, 18 dogs developed a series of metabolic disorders including obesity, dyslipidemia, oxidative stress and insulin resistance. In addition, a platelet hyperactivity state, characterized by increased agonist (arachidonic acid, ADP and collagen) induced platelet aggregation, platelet expression of adhesion molecules (P-selectin and GP IIb/IIIa), and platelet intracellular calcium concentration, was indicated. Cardiotonic pills showed a significant antioxidative activity by presenting an increase in plasma superoxide dismutase and decrease in erythrocyte glutathione, as well as a lipid-lowering effect (decrease in both plasma cholesterol and triglyceride). Either aspirin or cardiotonic pills could significantly reverse the platelet hypersensitivity and hyperfunction. Compared with aspirin, cardiotonic pills showed a more exaggerated inhibitory effect on platelet function (a significantly decreased collagen-stimulated platelet aggregation, and expression of adhesion molecules). In conclusion, cardiotonic pills inhibited platelet hyperfunction in dogs with insulin resistance. This inhibitory effect may mainly be explained by antioxidative activity and metabolic control.
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PMID:Inhibitory effects of cardiotonic pills on platelet function in dogs fed a high-fat diet. 1665 67

Statins reduce coronary heart disease risk by altering blood lipids and other mechanisms. One of the possible other mechanisms is through an effect on thrombosis. We assessed the effect of simvastatin 80 mg daily versus placebo given in a single blind crossover fashion on platelet size in response to standard ex vivo stimuli, a surrogate for platelet activation, in 12 subjects with type 2 diabetes and mixed dyslipidemia. Exposure to collagen, cold, and heat caused the expected changes in platelet volume. Contrary to our expectations, ex vivo platelet size during collagen and cold exposure increased by 2.6 and 1.7%, respectively (P < 0.05), during simvastatin treatment as opposed to the placebo period. We conclude that some of the effects of high dose simvastatin therapy on platelets may not necessarily be anti-atherogenic.
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PMID:The effect of high dose simvastatin on, platelet size in patients with, type 2 diabetes mellitus. 1692

Type 2 diabetes (DM-2) has become a major global health problem that has been fueled mainly by increasing obesity and aging of the population. Most studies show that arterial stiffening occurs across all age groups in both type 1 diabetes and DM-2, and among those with impaired fasting glucose, impaired glucose tolerance, and the metabolic syndrome. Arterial stiffening in DM-2 results, in part, from the clustering of hyperglycemia, dyslipidemia and hypertension, all of which may promote insulin resistance, oxidative stress, endothelial dysfunction, and the formation of pro-inflammatory cytokines and advanced glycosylation end-products. Likewise, aging may increase arterial stiffening by altering the proportions of elastin and collagen in the aorta. The consequences of arterial stiffening are increased pulse pressure, hypertension, and a greater risk of cardiovascular disease. Treatment strategies to reduce or prevent arterial stiffening include pharmacologic agents that block the renin-angiotensin-aldosterone system, relax vascular smooth muscle, enhance release of nitric oxide from endothelial cells, and break glycosylation end-product cross-links, and fish oil supplementation.
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PMID:Diabetes and arterial stiffening. 1707 13

Age-related changes in the hepatic sinusoid, called pseudocapillarization, may contribute to the pathogenesis of dyslipidemia. Caloric restriction (CR) is a powerful model for the study of aging because it extends lifespan. We assessed the effects of CR on the hepatic sinusoid to determine whether pseudocapillarization is preventable and hence a target for the prevention of age-related dyslipidemia. Livers from young (6 months) and old (24 months) CR and ad libitum fed (AL) F344 rats were examined using electron microscopy and immunohistochemistry. In old age, there was increased thickness of the liver sinusoidal endothelium and reduced endothelial fenestration porosity. In old CR rats, endothelial thickness was less and fenestration porosity was greater than in old AL rats. Immunohistochemistry showed that CR prevented age-related decrease in caveolin-1 expression and increase in peri-sinusoidal collagen IV staining, but did not alter the age-related increase of von Willebrand's factor. CR reduces age-related pseudocapillarization of the hepatic sinusoid and correlates with changes in caveolin-1 expression.
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PMID:Caloric restriction reduces age-related pseudocapillarization of the hepatic sinusoid. 1720 88

Functional and structural modifications in large arteries play an important role in the pathogenesis of cardiovascular diseases. The diabetes mellitus besides arterial hypertension and ageing can induce these alterations in different arterial sites, and so leading to the development of atherosclerosis and its cardiovascular consequences. The main functional change of large arteries is an increase of stiffness, while the main structural modification is an increase of the intima-media thickness of carotid artery, and both changes have been recognized in both type 1 and type 2 diabetes. The mechanisms of these structural and functional arterial modifications in diabetes include insulin resistance, collagen increase due to inadequate enzymatic glycation, endothelial and autonomic dysfunction. The increase of arterial stiffness is an independent cardiovascular risk marker in diabetic patients, and the treatment of diabetes per se and even of associated dyslipidemia and arterial hypertension can favorably modify these arterial changes.
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PMID:[Modifications of structural and functional properties of large arteries in diabetes mellitus]. 1750 24

Prediabetes [impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG)] is a major risk factor for T2DM as well as for cardiovascular disease and mortality. In the present study, the platelet aggregation and fibrinogen levels were investigated in prediabetic subjects who had no confounding factors such as hypertension, obesity or dyslipidemia. Thirty-nine subjects with prediabetes (24 IFG and 15 IGT) and age, sex and BMI matched 36 healthy controls were enrolled. Platelet aggregation, fibrinogen and hsCRP levels, HOMA-IR and HOMA-beta indexes were determined. Platelet aggregation induced by collagen, epinephrine or ADP was not different (p=0.93, p=0.90 and p=0.29, respectively) between two groups, whereas fibrinogen levels were significantly higher (p=0.006) in the prediabetics when compared to controls. hsCRP levels, HOMA-IR and HOMA-beta indexes in the two groups were not different. The power of the study was calculated according to the results and established as 0.97 for collagen, 0.95 for epinephrine and 0.83 for ADP. Despite the high plasma fibrinogen levels, the platelet aggregation in prediabetics was not different when compared to healthy controls. These data suggest that platelet aggregation may not be involved in the mechanism of prothrombotic state in prediabetic state.
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PMID:Platelet aggregation is not enhanced in patients with prediabetes. 1848 75


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