| 1. |
- Anwaar, I., et al.
(författare)
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Endothelial derived vasoactive factors and leukocyte derived inflammatory mediators in subjects with asymptomatic atherosclerosis
- 1998
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Ingår i: Angiology. - : SAGE Publications. - 0003-3197 .- 1940-1574. ; 49:12, s. 957-966
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Tidskriftsartikel (refereegranskat)abstract
- To clarify relationships between the (endothelial vasodilatory and vasoconstrictive function) and leukocyte inflammatory mediators in subjects with asymptomatic atherosclerosis, we measured (intraplatelet cyclic 3', 5' guanosine monophosphate [cGMP] and cyclic 3', 5' adenosine monophosphate [cAMP]), plasma endothelin (ET-1), and plasma neopterin in 197 subjects with asymptomatic atherosclerosis (median age 63 years, range 49-69 years). We measured neutrophil protease 4 (NP4), tumor necrosis factor (TNFμ), soluble tumor necrosis factor receptor-1 (sTNFR-1), and neutrophil gelatinase associated lipocalin (NGAL) in 152 of the 197 subjects. Intraplatelet cGMP correlated inversely with plasma ET-1 (r=-0.22; p=0.01), which confirms earlier in vitro data of the inhibitory effect of ET-1 on NO production and/or the cGMP mediated inhibitory effect of NO on ET-1 production. Plasma neopterin as well as NP4 correlated directly with intraplatelet cGMP (r=0.24; p<0.01 and r=0.33; p<0.001, respectively). Intraplatelet cAMP correlated directly with plasma TNFμ (r=0.17; p<0.05) and sTNFR-1 (r=0.20; p<0.05). The relationship between leukocyte derived inflammatory mediators and intraplatelet cyclic nucleotides suggest an antiaggregating effect of leukocytes upon platelets, which may constitute a negative feedback mechanism that inhibits platelet activation during the atherosclerotic inflammatory process.
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| 2. |
- Anwaar, I., et al.
(författare)
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Hormone replacement therapy in healthy postmenopausal women. Effects on intraplatelet cyclic guanosine monophosphate, plasma endothelin-1 and neopterin
- 2000
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 247:4, s. 463-470
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To evaluate beneficial effects of postmenopausal hormone replacement therapy (HRT) on endothelial function, measured as intraplatelet cyclic guanosine monophosphate (cGMP, mediator of nitric oxide), cyclic adenosine monophosphate (cAMP, mediator of prostacyclin) and plasma endothelin-1 (ET-1), and on monocyte activation, measured as plasma neopterin. Design. Part 1: double-blind randomized trial for 3 months; part 2: open study for 9 months. Setting. The study was performed at the Department of Endocrinology, University Hospital, Malmo, Sweden. Subjects. Fifty-one postmenopausal women participated in part 1 and 46 in part 2. Inclusion criteria included a history of amenorrhoea for at least 6 months before the study and body mass index ≥ 24 kg m-2 Intervention. Randomization for either placebo (n = 24) or HRT (n = 27). HRT was given as 2 mg oestradiol valerate for the first 3 months with the addition of 10 mg medroxyprogesterone for 10 days every third month thereafter. Measurements. Performed at baseline and after 3 and 12 months of the study. Results. In the HRT group, intraplatelet cGMP increased from 0.56 (0.35-0.94) to 0.61 (0.423.40) and 0.65 (0.43-1.08) pmol (109 platelets)-1 after 3 and 12 months, respectively (P = 0.01), whereas plasma ET-1 decreased from 3.2 (1.1.-6.8) to 2.0 (0.8-5.1) and 1.8 (0.4-15.4) pg mL-1 (P < 0.001). Intraplatelet cAMP and plasma neopterin were unchanged. When smokers (n = 15) and non-smokers (n = 12) in the HRT group were analysed separately, significant effects were seen only amongst smokers. The control group showed unchanged levels of cGMP, cAMP, ET-1 and neopterin. Conclusions. These data suggest beneficial effects of HRT on endothelial function which may account for anti-atherogenic effects of HRT in postmenopausal women, especially in smokers. No effects of HRT were seen upon monocyte activation.
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| 3. |
- Anwaar, I., et al.
(författare)
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Increased plasma endothelin-1 and intraplatelet cyclic guanosine monophosphate in men with disturbed glucose metabolism
- 2000
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Ingår i: Diabetes Research and Clinical Practice. - 0168-8227. ; 50:2, s. 127-136
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Tidskriftsartikel (refereegranskat)abstract
- Plasma endothelin-1, the nitric oxide (NO) mediator intraplatelet cyclic guanosine monophosphate (cGMP), the prostacyclin mediator cyclic adenosine monophosphate (cAMP) and the macrophage derived inflammatory mediator plasma neopterin were measured in men with Type 2 diabetes mellitus (n = 91), impaired glucose tolerance (IGT; n = 51), previously abnormal glucose tolerance (PAGT; n = 20), and 34 healthy control men. Plasma endothelin-1 was higher in men with Type 2 diabetes mellitus than in controls [4.1 (1.0-14.3) vs. 2.1 (0.2-8.7) ng/l; P < 0.001). Intraplatelet cGMP was higher in men with PAGT [0.84 (0.57-2.76) pmol/109 platelets; P < 0.05], IGT [0.85 (0.48-3.53); P < 0.001] and Type 2 diabetes mellitus [0.90 (0.47-3.86); P < 0.001] than in controls [0.70 (0.42-1.70]. No differences existed between groups concerning intraplatelet cAMP or plasma neopterin. Plasma endothelin-1 correlated with fasting plasma glucose (r = 0.33; P < 0.001) and HbA1(c) (r = 0.29; P < 0.001). In conclusion, elevated plasma endothelin-1 in Type 2 diabetes mellitus and its relationship to glucose and HbA1(c) suggest a putative role for endothelin-1 in diabetic endothelial cell damage. Increased cGMP indicating enhanced production/activity of NO suggests that factors other than reduced NO activity contribute to enhanced platelet aggregation in diabetes. (C) 2000 Elsevier Science Ireland Ltd.
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| 4. |
- Anwaar, I., et al.
(författare)
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Increasing levels of leukocyte-derived inflammatory mediators in plasma and cAMP in platelets during follow-up after acute cerebral ischemia
- 1998
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Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 8:6, s. 310-317
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory mediators secreted by activated leukocytes play a role in the pathogenesis of atherosclerosis. They may also affect the production of vasodilatory and platelet antiaggregatory factors such as nitric oxide (NO) and prostacyclin (PGI2) from the vascular endothelium. Production of NO and PGI2, the effecs of which are mediated by cyclic 3',5'-guanosine monophosphate (cGMP) and cyclic 3',5'-adenosine monophosphate (cAMP), respectively, is disturbed in atherosclerosis, whereas increased NO levels have been found in acute cerebral ischemia. To investigate leukocyte activation and its possible influence upon endothelial function in cerebral ischemia we measured plasma neutrophil gelatinase-associated lipocalin (NGAL) and soluble tumor necrosis factor receptor protein-1 (sTNFR-1) by ELISA, and intraplatelet cAMP and cGMP by radioimmunoassay in 59 patients with acute ischemic stroke or transient ischemic attack (mean age 71 years, 27 males) and after a 1-year follow-up in 57/59 (97%) patients. NGAL (152 ± 58 vs. 126 ± 48 μg/l), sTNFR-1 (3.50 ± 2.2 vs. 2.59 ± 1.31 μg/l), and cAMP(5.12 ± 1.71 vs. 4.06 ± 0.92 pmol/109 platelets) were higher (p < 0.001) after follow-up than in acute cerebral ischemia. At follow-up sTNFR-1 and cGMP partially correlated (r = 0.31; p < 0.05), controlling for age and platelet count. In conclusion, plasma NGAL and sTNFR-1 and intraplatelet AMP increase after acute cerebral ischemia, indicating chronic inflammatory activity and endothelial activation. Plasma sTNFR-1 levels are related to intraplatelet cGMP levels.
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| 5. |
- Anwaar, I., et al.
(författare)
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Intraplatelet cyclic 3'-5' guanosine monophosphate is related to serum cholesterol
- 1996
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Ingår i: International Angiology. - 0392-9590. ; 15:3, s. 201-206
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Tidskriftsartikel (refereegranskat)abstract
- Nitric oxide (NO) exerts its vasodilator and antiaggregatory effects through activation of soluble guanylate cyclase and the consequent increase in the concentration of cGMP in target cells. We conducted this study in order to evaluate relationships between intraplatelet cGMP levels and risk factors for atherosclerosis in middle aged subjects. Intraplatelet cGMP was determined by radioimmunoassay and related to age, BMI, blood pressure, antihypertensive treatment, total, LDL and HDL cholesterol, triglycerides, blood glucose, HbA1c, smoking habit and intimal thickness of the common carotid artery in 265 subjects participating in a health survey (age 59 ± 6 years, range 48-68 years, 121 females, 144 males). Intraplatelet cGMP concentration was inversely correlated with total serum cholesterol (r = -0.18; p < 0.01) and HDL cholesterol (r = -0.14, p < 0.05) as well as with platelet count (r = -0.29; p < 0.001). When platelet count was adjusted for, only the correlation between total serum cholesterol and cGMP remained significant. No significant correlations could be demonstrated between intraplatelet cGMP levels and measurable parameters of atherosclerosis. Lower levels of the vasodilating and antiaggregating mediator cGMP in platelets are related to higher levels of serum total cholesterol. These results favour the hypothesis of a relationship between lipid levels and NO associated vasodilator and antiaggregating fuction in atherosclerosis.
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| 6. |
- Gottsäter, A., et al.
(författare)
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Homocysteine is related to neopterin and endothelin-1 in plasma of subjects with disturbed glucose metabolism and reference subjects
- 2000
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Ingår i: Angiology. - : SAGE Publications. - 0003-3197 .- 1940-1574. ; 51:6, s. 489-497
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Tidskriftsartikel (refereegranskat)abstract
- Hyperhomocysteinemia is an independent risk factor for vascular disease. In order to evaluate relations between hyperhomocysteinemia and endothelial and leukocyte function, the investigators related homocysteine to indices of endothelial function (plasma endothelin-1 [p-ET-1] and intraplatelet levels of the nitric oxide [NO] and prostacyclin mediators 3'-5' guanosine monophosphate [cGMP] and cyclic 3'-5' adenosine monophosphate [cAMP]) and the monocyte-derived inflammatory mediator neopterin in 168 men (mean age 69, range 49-72 years) with disturbed glucose metabolism and a reference group of 52 male subjects (mean age 70, range 61-79 years). Among the 168 patients with disturbed glucose metabolism plasma (p)-homocysteine correlated- significantly with age (r = 0.20; p<0.01), glycosylated hemoglobin (HbA(1c)) (r = 0.17; p<0.05), triglycerides (r = 0.20; p<0.05), intraplatelet GMP (r = 0.16; p<0.05), p-ET-1 (r = 0.21; p<0.05), and p-neopterin (r = 0.31; p<0.001). The correlation between p-homocysteine and p-ET-1 persisted (p<0.01) in multiple regression analysis. Among the 52 reference subjects p- homocysteine correlated significantly with p-ET-1 (r = 0.32; p<0.05) and p- neopterin (r = 0.37; p<0.01). The correlation between p-homocysteine and p- neopterin persisted (p<0.05) in multiple regression analysis. In conclusion, homocysteine is related to neopterin and endothelin-1 in plasma of subjects with disturbed glucose metabolism and in reference subjects, suggesting that homocysteine exerts its deleterious effects on vascular function through interference with endothelial and leukocyte function.
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| 7. |
- Gottsäter, Anders, et al.
(författare)
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Increasing plasma fibrinogen, but unchanged levels of intraplatelet cyclic nucleotides, plasma endothelin-1, factor VII, and neopterin during cholesterol lowering with fluvastatin
- 1999
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Ingår i: Blood Coagulation and Fibrinolysis. - : Ovid Technologies (Wolters Kluwer Health). - 0957-5235. ; 10:3, s. 133-140
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Tidskriftsartikel (refereegranskat)abstract
- Lipid-lowering statin treatment reduces cardiovascular morbidity and mortality and improves endothelial function in patients with hypercholesterolemia. The aim of the present study was to evaluate plasma levels of fibrinogen, factor VII, and the macrophage-derived inflammatory mediator neopterin during lipid lowering. In addition, the endothelial production of platelet antiaggregatory and vasodilatory factors such as nitric oxide and prostacyclin, and vasoconstrictive factors such as endothelin-1, was assessed. Plasma fibrinogen, factor VII, endothelin-1, and the neopterin and intraplatelet nitric oxide and prostacyclin mediators cyclic 3'-5'guanosine monophosphate (cGMP) and cyclic 3'-5'adenosine monophosphate (cAMP) were measured before and 6 months after the institution of treatment with fluvastatin in 17 patients (eight men and nine women, median age 60 years) with vascular disease and previously untreated hypercholesterolemia. After 6 months, a decrease of 1.62 mmol/l [1.26-2.18 (19%); P < 0.01] was noted in levels of total cholesterol, and a decrease of 1.70 mmol/l [1.52-2.30 (28%); P < 0.01] in levels of low-density lipoprotein cholesterol. Plasma levels of fibrinogen had increased [from 4.81 g/l (4.26- 5.27) to 5.17 g/l (4.81-5.67); P < 0.05], whereas no significant changes had occurred in intraplatelet levels of cGMP [decrease by 0.05 pmol/109 platelets (-0.17 to 0.24); NS], cAMP [decrease by 0.13 pmol/109 platelets (- 0.37 to 0.86); NS], plasma endothelin-1 [decrease by 0.05 pg/ml (-0.60 to 0.70); NS], plasma factor VII [from 1.14 IE/ml (0.58-1.38) to 1.22 IE/ml (0.96-1.46); NS], or plasma neopterin [from 8.6 nmol/l (7.1-11.5) to 8.7 nmol/l (7.9-11.3); NS]. In conclusion, during cholesterol-lowering treatment with fluvastatin, plasma levels of fibrinogen increased whereas intraplatelet cyclic nucleotide levels and plasma endothelin-1, factor VII and neopterin levels were unchanged.
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