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)

The diabetic heart shows increased fibrosis, which impairs cardiac function. Endothelin (ET)-1 and nuclear factor-kappaB (NF-kappaB) interactively regulate fibroblast growth. We have recently demonstrated that Punica granatum flower (PGF), a Unani anti-diabetic medicine, is a dual activator of peroxisome proliferator-activated receptor (PPAR)-alpha and -gamma, and improves hyperglycemia, hyperlipidemia, and fatty heart in Zucker diabetic fatty (ZDF) rat, a genetic animal model of type 2 diabetes and obesity. Here, we demonstrated that six-week treatment with PGF extract (500 mg/kg, p.o.) in Zucker diabetic fatty rats reduced the ratios of van Gieson-stained interstitial collagen deposit area to total left ventricular area and perivascular collagen deposit areas to coronary artery media area in the heart. This was accompanied by suppression of overexpressed cardiac fibronectin and collagen I and III mRNAs. Punica granatum flower extract reduced the up-regulated cardiac mRNA expression of ET-1, ETA, inhibitor-kappaBbeta and c-jun, and normalized the down-regulated mRNA expression of inhibitor-kappaBalpha in Zucker diabetic fatty rats. In vitro, Punica granatum flower extract and its components oleanolic acid, ursolic acid, and gallic acid inhibited lipopolysaccharide-induced NF-kappaB activation in macrophages. Our findings indicate that Punica granatum flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats, at least in part, by modulating cardiac ET-1 and NF-kappaB signaling.
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PMID:Pomegranate flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats: modulation of cardiac endothelin-1 and nuclear factor-kappaB pathways. 1630 13

Most collagen diseases are more common in women except polyarteritis nodosa, but aging makes this gender difference smaller in some of the diseases. In systemic lupus erythematosus the incidence difference between men and women diminishes while Sjogren syndrome is more common in women at all ages. Diabetes mellitus and hyperlipidemia are also very common complications with steroid treatment. DM is more common in those aged over 45 years old. On the contrary, hyperlipidemia is common at all ages with the peak in those 45-54 years old and only 22% over 75 years old have hyperlipidemia. According to the introduction of aggressive therapy for rheumatoid arthritis, complications in the elderly should be carefully managed.
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PMID:[Age and gender difference in rheumatology]. 1640 3

To investigate the physiological role of novel genes and proteins in platelet activation, various knockout mice have been produced. A number of standard inbred mouse strains each possessing genetically unique characters such as high tumor generation, hyperglycemia or hyperlipidemia, have been bred. In breeding knockout mice for investigation of specific physiological functions, appropriate selection of parental or backcross strains is necessary. Thus, examination of strain-specific platelet characteristics is important. In the present study, platelet aggregation responses of 13 laboratory mouse strains, 129/Sv, A, AKR, BALB/c, C3H/He, C57BL/6J, CBA, DBA/1, DBA/2, ddY, FVB, ICR, and NZW, and the diabetic strain C57BL/KsJ db/db, were compared. Marked strain differences were observed in ADP- and collagen-induced platelet aggregation. The highest responses with both were seen in AKR/J and NZW/N, whereas the lowest were seen in DBA/2 and DBA/1. There was a 5-fold difference in the platelet aggregation threshold index (PATI) for ADP-induced PRP aggregation between AKR/J (0.6 microM) and DBA/2 (3.0 microM). With whole blood aggregation, the highest response was seen in AKR, whereas the lowest was seen in DBA/2 and DBA/1. The present study demonstrated that there is considerable strain difference in platelet aggregation among laboratory mice, which should be taken into account in backcrossing knockout strains.
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PMID:Genetic strain differences in platelet aggregation of laboratory mice. 1654 75

A 41-year-old man with hypertension and hyperlipidemia who complained of left hemiparesis after a temporal headache was admitted to our hospital. A cervical MRI with gadolinium enhancement revealed an intramural hematoma is compatible with right extracranial internal carotid artery dissection. Two weeks later, he complained of sudden onset of pain in the right side of his neck. The right extracranial internal carotid artery dissection followed by the right extracranial vertebral artery dissection was diagnosed. Spontaneous cervical artery dissection (SCAD) is one of the causes of stroke in young adults. The pathogenesis of SCAD remains unknown. Minor trauma like an excessive sneeze, migraine, and connective tissue disorders such as fibromuscular dysplasia and Ehlers-Danlos syndrome are well-known as risk factors for SCAD. Pathologically skin collagen abnormalities have been seen in German patients with SCAD without clinical evidence for any specific connective tissue disorder. We examined the ultrastructural morphology of the Japanese patient's dermal connective tissue components by electron microscopy. The patient's collagen fibers contained fibrils with highly variable diameters, and there were other ultrastructural abnormalities, including flower-like fibrils and large-diameter composite fibrils. This is the first report of a case of ultrastructural abnormalities of dermal connective tissue in a Japanese patient with SCAD.
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PMID:[Skin collagen abnormalities in a Japanese patient with extracranial internal carotid artery dissection followed by extracranial vertebral artery dissection]. 1661 39

Genetic mouse models provide a unique opportunity to investigate gene function in the natural course of the disease. Although diabetic nephropathy (DN) in models of type II diabetes has been well characterized, diabetic renal disease in hypoinsulinemic diabetic mice is still incompletely understood. Here, we characterized renal changes in the pdx1(PB)-HNF6 transgenic mouse that exhibits beta-cell dysfunction and nonobese hypoinsulinemic diabetes. Male transgenic mice developed hyperglycemia by the age of 7 wk and survived for over 1 yr without insulin treatment. Diabetes ensued earlier and progressed more severely in the HNF6 males than the females. The HNF6 males exhibited albuminuria as early as 10 wk of age, and the urinary albumin excretion increased with age, exceeding 150 microg/24 h at 11 mo of age. Diabetic males developed renal hypertrophy after 7 wk of age, whereas glomerular hyperfiltration was not observed in the mice. Hypertension and hyperlipidemia were not observed in the diabetic mice. Histological analysis of the HNF6 kidneys displayed diabetic glomerular changes, including glomerular enlargement, diffuse mesangial proliferation and matrix expansion, thickened glomerular basement membrane, and arteriolar hyalinosis. Mesangial matrix accumulation increased with age, resulting in nodular lesions by 44 wk of age. Immunohistochemistry showed accumulation of type IV collagen and TGF-beta1 in the mesangial area. No significant immune complex deposition was observed in the HNF6 glomeruli. Thus the HNF6 mouse exhibits diabetic renal changes that parallel the early phase of human DN. The model should facilitate studies of genetic and environmental factors that may affect DN in hypoinsulinemic diabetes.
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PMID:Characterization of diabetic nephropathy in a transgenic model of hypoinsulinemic diabetes. 1670 46

Plasma lipid composition, platelet aggregation, cholesterol (Ch)/glycoprotein IIb-IIIa (GP) and phospholipid (Ph)/GP molar ratios, fatty acid composition and structural order (1, 6-diphenyl-1, 3, 5-hexatriene (DPH) fluorescence anisotropy at 35 degrees C (r(DPH,35)) of human platelet plasma membranes (HPPM) were measured in four DPH,35 groups of hyperlipidemic patients (II: plasma Ch < 250 mg/dl and TG (triglycerides) <220 mg/dl, n = 21; III: Ch > 250 mg/dl and TG < 220 mg/dl, n = 23; IV: Ch < 250 mg/dl and TG > 220 mg/dl, n = 18; and V: Ch > 250 mg/dl and TG > 220 mg/dl, n = 12) and compared with those of the control group (I). Our results were: (i) in groups III, IV and V the HPPM (Ch + Ph)/GP molar ratio increased 7.0+/-7.7% (mean SD); (ii) the Ph/GP molar ratio increased significantly in groups III, IV and V, but most in IV and V, while the Ch/GP molar ratio increased only in groups III and V; (iii) the mean relative increase of Ch with respect to Ph in the HPPM of groups III, IV and V was 140% 21% and 54%, respectively; (iv) the Ch/GP molar ratio was correlated with LDL-Ch (0.41+/-0.16, P < 0.002, n = 55, for all the subjects and 0.60+/-0.11, P < 2.10(-4), n = 33, for subjects with TG < 220 mg/dl), however, it was totally uncorrelated with HDL-Ch; (v) the HPPM Ch/Ph molar ratio was positively correlated with plasma Ch (r = 0.51+/-0.08, P < 1.10(-6), n = 83) and with (LDL + HDL) Ch (r = 0.64+/-0.07, P < 1.10(-6), n = 73), the former correlation increased significantly ( r = 0.67+/-0.07, P < 1.10(-6), n = 53) when done only for subjects with TG < 220 mg/dl; (vi) the Ch/Ph molar ratio was only increased in group III (0.70+/-0.03, P < 3.10(-5), n = 23) and decreased in group IV (0.62+/-0.02, P < 0.001, n = 18); (vii) the fatty acid/GP molar ratio was significantly increased in groups IV and V, however, a significant absolute and relative increase of C16:0 and C18:1 was observed only in severe hypertriglyceridemia (> 500 mg/dl), together with a relative decrease of C18:0 and C20:4 ( n - 6); (viii) the HPPM structural order, as probed by r(DPH,35), was negatively correlated with DPH,35 plasma TG (r =- 0.61+/-0.10, P < 4.10(-5), n = 39), the Ph/GP molar ratio (r =-0.58+/-0.10, P < 2.10(-4), n = 39) and the the (C18:1 + C18:2))/GP molar ratio (r =- 0.80+/-0.05, P < 1.10(-6), n = 39), however, it was independent of plasma and HPPM Ch; (ix) the higher HPPM Ch/Ph molar ratio in group III was associated (r = 0.58+/-0.12, P < 0.005, n = 22) with a moderately higher platelet reactivity to collagen. We conclude that Ch and Ph were distinctly incorporated to HPPM in the different groups of hyperlipidemia and, therefore, that the absolute increase of Ch and Ph was more informative to understand the structural and functional modifications of the HPPM in hyperlipidemias, than the Ch/Ph molar ratio. On the other hand, the r was sensitive to the DPH,35 increase in the content of HPPM Ph and C18:1 + C18:2 and it was insensitive to the increase in the Ch content.
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PMID:Distinct cholesterol and phospholipid incorporation at the platelet plasma membrane of hyperlipidemic subjects: structural order and function. 1679 20

Retinal vein occlusion (RVO) is the most common retinal vascular disorder second to diabetic retinopathy. The main risk factors in patients with RVO are hypertension, diabetes, hyperlipidemia, increased blood viscosity and glaucoma. The pathogenesis of RVO has not yet been clarified. In these events platelets could play a very important role. In the present study the platelet response to collagen was deeply investigated. Experiments were carried out on a selected group of RVO patients, which were compared to a group of healthy subjects matched for age, sex, clinical and metabolic characteristics. In resting and activated platelets of both groups of subjects p72syk phosphorylation, phospholipase Cgamma2 phosphorylation, protein kinase C activation, intra-cellular calcium levels and nitric oxide formation were measured. Results show that platelets of patients were more responsive to collagen or ADP than healthy subjects and that the response was significantly different (p < 0.0005) at low concentrations of these agonists. In platelets of patients stimulated with collagen increased phosphorylation of p72syk and phospholipase Cgamma2 was found. Also protein kinase C was more activated in patients. In addition intracellular calcium rise induced by collagen was significantly higher in patients than in healthy subjects. RVO patients showed a lower basal level of nitric oxide both in resting and stimulated platelets compared to healthy subjects. Altogether these results suggest that the platelet hyperaggregability described in patients might be an important factor in the development of RVO contributing to the thrombogenic effects.
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PMID:Platelet activation by collagen is increased in retinal vein occlusion. 1726 50

Rats are employed to investigate the role of platelets in thrombus formation under flow conditions in vivo and to evaluate the pre-clinical potential of antiplatelet drugs. While Wistar and Sprague-Dawley (SD) strains are commonly used in thrombosis models, a number of rat strains have been established. Each strain possesses genetically unique characteristics such as hypertension, hyperglycemia or hyperlipidemia. The appropriate selection of a strain might have advantages for physiological and pharmacological studies. Comparative investigation of platelet aggregation among laboratory strains of rats is useful for the development of thrombosis models. In the present study, platelet aggregation response in eight laboratory rat strains, ACI, Brown Norway (BN), Donryu, Fischer 344 (F344), LEW, SD, Wistar and WKAH, were compared. Considerable strain differences were observed in ADP-, collagen- and TRAP-induced platelet aggregation. SD and BN are high-platelet-aggregation strains, while F344 and ACI are low-response strains. In the arteriovenous shunt thrombosis model, SD formed larger thrombi than F344 and Wistar rats. In the FeCl(3)-induced thrombosis model with the carotid artery, the time to occlusion of SD was significantly shorter than of F344 and ACI rats. F344 and ACI rats had significantly increased bleeding times compared with SD rat. The present study demonstrates that there are considerable strain differences in platelet aggregation among laboratory rats, which reflect thrombus formation.
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PMID:Genetic strain differences in platelet aggregation and thrombus formation of laboratory rats. 1739 31

Peroxisome proliferator-activated receptor alpha (PPARalpha) ligands are medications used to treat hyperlipidaemia and atherosclerosis. Increasing evidence suggests that these agents are immunosuppressive. In the following studies we demonstrate that WY14,643, a PPARalpha ligand, attenuates expression of anti-glomerular basement membrane disease (AGBMD). C57BL/6 mice were fed 0.05% WY14,643 or control food and immunized with the non-collagenous domain of the alpha3 chain of Type IV collagen [alpha3(IV) NC1] in complete Freund's adjuvant (CFA). WY14,643 reduced proteinuria and greatly improved glomerular and tubulo-interstitial lesions. However, the PPARalpha ligand did not alter the extent of IgG-binding to the GBM. Immunohistochemical studies revealed that the prominent tubulo-interstitial infiltrates in the control-fed mice consisted predominately of F4/80(+) macrophages and WY14,643-feeding decreased significantly the number of renal macrophages. The synthetic PPARalpha ligand also reduced significantly expression of the chemokine, monocyte chemoattractant protein (MCP)-1/CCL2. Sera from mice immunized with AGBMD were also evaluated for antigen-specific IgGs. There was a significant increase in the IgG1 : IgG2c ratio and a decline in the intrarenal and splenocyte interferon (IFN)-gamma mRNA expression in the WY14,643-fed mice, suggesting that the PPARalpha ligand could skew the immune response to a less inflammatory T helper 2-type of response. These studies suggest that PPARalpha ligands may be a novel treatment for inflammatory renal disease.
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PMID:WY14,643, a PPARalpha ligand, attenuates expression of anti-glomerular basement membrane disease. 1788 25

Platelet hyperactivity is likely to contribute to the progression of atherogenesis and organized thrombus formation on vascular surfaces. The purpose of this study was to examine the effect of hypercholesterolemia on the cholesterol content of platelets, on platelet responsiveness and other platelet indices using platelets from 5 groups of age-matched subjects (n = 30 each), which includes healthy controls. All groups except controls had a high plasma lipid profile. While subjects in group I had only hyperlipidemia, those in groups II and III had hyperlipidemia in conjunction with diabetes mellitus and hypertension, respectively. The fourth group consisted of patients with confirmed coronary artery disease (CAD). The parameters studied include packed cell volume of platelets (platelet crit), platelet distribution width (PDW), platelet cholesterol and platelet aggregation in response to adenosine diphosphate and collagen. All the patient groups showed increased platelet aggregation (p < 0.05) and low platelet crit compared with controls (p < 0.05). In addition, platelet cholesterol was increased in patients with coronary disease, hyperlipidemia and diabetes mellitus (p < 0.05) but not in patients with hypertension (p > 0.05); PDW was high only in CAD (p < 0.05). A higher PDW indicated a prothrombotic tendency in CAD patients. Our data suggest that hyperlipidemia increases the lipid content in platelets and enhances their reactivity. Hyperactive platelets with increased platelet cholesterol may contribute to accelerated atherogenesis associated with CAD.
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PMID:Increased platelet cholesterol and decreased percentage volume of platelets as a secondary risk factor for coronary artery disease. 1833 14


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