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 effect of hyperlipemia associated with diabetes on the contractility of resistance arteries to prostaglandin F2alpha (PGF2alpha) was investigated employing 4 weeks simultaneously hyperlipemic-diabetic (HD), hyperlipemic (H), diabetic (D) and normal hamsters (controls, C). The isometric force produced by explanted arteries in the presence of 10(-8) to 10(-5) M PGF2alpha was recorded by the myograph technique. The results showed that compared with controls, the contractile response to 10(-5) M PGF2alpha was approx. 2 fold increased in HD group, and approx. 1.75 and 1.62-fold enhanced in H and D groups, respectively. Activation of protein kinase C with 10(-6) M phorbol 12-myristate 13-acetate increased the contractility to PGF2alpha in all groups and particularly in HD hamsters (approx. 10.16-fold). Inhibition of cyclooxygenase by indomethacin increased approx. 1.81-fold the arterial contractility to PGF2alpha in C group, whereas in H, D and HD hamsters had no effect. Blockage of Ca(2+)-activated K(+)-channels with 10(-3) M tetraethylammonium augmented the contraction to PGF2alpha approx. 6.43-fold in C group, and at significantly lower levels in H, D and HD groups, i.e. approx. 3.84, 3.72 and 3.33-fold, respectively. The results validate two conclusions: (i) simultaneous insult of hyperlipemia-hyperglycemia is associated with the highest contractility of the resistance arteries to PGF2alpha; the highest circulating glucose and cholesterol levels, and the enhancement in the protein kinase C pathway underlay the augmented contractility; (ii) no matter the pathology induced (hyperlipemia, diabetes or both simultaneously) a common dysfunctional response to PGF2alpha was installed; this consists in a reduced effect of cyclooxygenase inhibition, and a altered activity of Ca(2+) dependent K(+) channels.
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PMID:The contractile response of the mesenteric resistance arteries to prostaglandin F2alpha; effects of simultaneous hyperlipemia-diabetes. 1501 13

An open-label prospective cross-over trial was performed to evaluate the antioxidative effect of fluvastatin in Japanese type 2 diabetics with hyperlipidemia. The study subjects were 10 patients who were on pravastatin (10 mg/day) or simvastatin (5 mg/day). After at least 12 weeks of continuous pravastatin or simvastatin therapy, the drugs were washed out for 12 weeks and replaced with fluvastatin (30 mg/day), then the treatment was continued for another 12 weeks. Total cholesterol and LDL cholesterol were efficiently and comparably reduced by all three statin agents. There were no differences in serum parameters of oxidative stress such as malondialdehyde-modified low-density lipoprotein, thiobarbituric acid-reactive substances, and 8-iso-prostaglandin F2alpha between pravastatin/simvastatin and fluvastatin. However, fluvastatin, but not pravastatin/simvastatin, significantly reduced 3,5,7-cholestatriene in erythrocyte membrane, representing the extent of membrane cholesterol peroxidation. Our data demonstrated that fluvastatin has a unique anti-oxidative effect in patients with type 2 diabetes and hyperlipidemia, compared with other statins.
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PMID:Anti-oxidative effect of fluvastatin in hyperlipidemic type 2 diabetic patients. 1586 58

Low concentrations of selenium (Se) predict mortality and cardiovascular diseases in some populations. The effect of Se on in vivo indicators of oxidative stress and inflammation, two important features of atherosclerosis, in human populations is largely unexplored. This study investigated the longitudinal association between serum selenium (s-Se) and a golden standard indicator of oxidative stress in vivo (8-iso-prostaglandin F2alpha, a major F2-isoprostane), an indicator of cyclooxygenase (COX)-mediated inflammation (prostaglandin F2alpha), high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and serum amyloid A protein (SAA) in a follow-up study of 27 years. The s-Se was measured in 615 Swedish men at 50 years of age in a health investigation. The status of oxidative stress and inflammation was evaluated in a re-investigation 27 years later by quantification of urinary 8-iso-PGF2alpha and 15-keto-dihydro-PGF2alpha (a major metabolite of PGF2alpha) and serum hsCRP, SAA and IL-6. Men in the highest quartile of s-Se at age 50 had decreased levels of 8-iso-PGF2alpha compared to all lower quartiles and decreased levels of PGF2alpha compared to all lower quartiles at follow-up. These associations were independent of BMI, diabetes, hyperlipidemia, hypertension, smoking, alpha-tocopherol and beta-carotene at baseline. The s-Se was not associated with hsCRP, SAA or IL-6 at follow-up. In conclusion, high concentrations of s-Se predict reduced levels of oxidative stress and subclinical COX-mediated (but not cytokine-mediated) inflammation in a male population. The associations between Se, oxidative stress and inflammation, respectively, might be related to the proposed cardiovascular protective property of Se.
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PMID:Serum selenium predicts levels of F2-isoprostanes and prostaglandin F2alpha in a 27 year follow-up study of Swedish men. 1603 56

Diabetes is a risk factor of ischemic heart disease, cerebral ischemia, and atherosclerosis, in which endothelial dysfunction plays a role in the pathogenesis. We examined vascular responses in the aorta of pre-diabetic db/db mice with normoglycemia, hyperlipidemia, and hyperinsulinemia (6 weeks old), and diabetic db/db mice with hyperglycemia, hyperlipidemia, and hyperinsulinemia (11 weeks old) in comparison with age-matched non-diabetic db/+ mice. Prostaglandin F2alpha (PGF2alpha)-induced contraction was significantly enhanced in the aorta of diabetic but not pre-diabetic db/db mice compared to age-matched non-diabetic db/+ mice. Acetylcholine (ACh), adenosine-5'-diphosphate (ADP), NaF, a G protein activator and A-23187, a Ca-ionophore, caused endothelium-dependent and nitric oxide (NO)-mediated relaxation, and sodium nitroprusside (SNP), an NO donor, caused endothelium-independent relaxation in the pre-contracted aorta of db/db mice. Maximal endothelium-dependent ACh-induced relaxation was reduced in diabetic but not pre-diabetic db/db mice compared to age-matched db/+ mice, while maximal SNP-induced relaxation was not different between diabetic and non-diabetic mice. ACh-induced relaxation in diabetic db/db mice was not affected by ozagrel, a thromboxane A2 (TXA2) synthetase inhibitor, or acetylsalicylic acid (aspirin), a cyclooxygenase inhibitor, suggesting no involvement of endogenous TXA2 or prostanoids in the reduction of relaxation. Maximal endothelium-dependent ADP-, A-23187-, and NaF-induced relaxation was not reduced in diabetic db/db mice. EC50 values for ACh- and SNP-induced relaxation were increased in diabetic but not pre-diabetic db/db mice, suggesting decreases in sensitivity to NO in diabetic mice. Two-week treatment with KV-5070, a PPARgamma agonist, lowered plasma glucose, triglyceride (TG), and insulin but not cholesterol, and reversed the reduced ACh-induced relaxation. In conclusion, ACh-induced endothelium-dependent relaxation is impaired in diabetic db/db mice, probably due to the dysfunction of ACh receptors and/or receptor-G protein coupling. Endothelial dysfunction was not genetic and was considered to be initiated primarily by hyperglycemia, and was improved by anti-diabetic treatment with a PPARgamma agonist.
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PMID:Impairment of endothelium-dependent ACh-induced relaxation in aorta of diabetic db/db mice--possible dysfunction of receptor and/or receptor-G protein coupling. 1822 1