| 1. |
- De Basso, Rachel, et al.
(författare)
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Increased cardiovascular risk without generalized arterial dilating diathesis in persons who do not have abdominal aortic aneurysm but who are first-degree relatives of abdominal aortic aneurysm patients
- 2015
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Ingår i: Clinical and Experimental Pharmacology and Physiology. - : Wiley. - 1440-1681 .- 0305-1870. ; 42:6, s. 576-581
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Tidskriftsartikel (refereegranskat)abstract
- There is a strong genetic predisposition towards abdominal aortic aneurysm (AAA), but it is unknown whether persons without AAA but with first-degree relatives who are AAA patients have a generalized dilating diathesis, defect arterial wall mechanics, or increased cardiovascular risk. The aim of the study was to investigate arterial diameters and wall mechanics at multiple arterial sites in these subjects and compare them with controls without a family history of AAA. This study included 118 first-degree relatives of patients with AAA and 66 controls (age: 40-80years). The abdominal aorta, common carotid artery, common femoral artery, and popliteal artery were investigated by echo-tracking ultrasound. The relatives had no arterial dilatation, but they did tend to have smaller diameters than controls. Relatives had a higher heart rate, diastolic blood pressure, and mean arterial pressure than controls. The distensibility coefficient and the compliance coefficient were decreased in all arteries in male relatives, adjusted for age and smoking; these coefficients were normalized after adjustment for mean arterial pressure and heart rate. Female relatives had a lower compliance coefficient in the abdominal aorta, adjusted for age and smoking. After adjustment for mean arterial pressure and heart rate, the difference disappeared. No general arterial dilatation in relatives without AAA was found, supporting the hypothesis that the dilating diathesis is linked to the aneurysmal manifestation in the abdominal aorta. Although the threat of aneurysmal dilatation and rupture seems to be lacking in these subjects, heart rate, blood pressure, and arterial wall stiffness were all increased, which may indicate a higher risk of developing cardiovascular morbidity and mortality.
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| 2. |
- De Basso, Rachel, et al.
(författare)
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Increased carotid plaque burden in men with the fibrillin-1 2/3 genotype
- 2014
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Ingår i: Clinical and Experimental Pharmacology and Physiology. - : Wiley. - 1440-1681 .- 0305-1870. ; 41:9, s. 637-642
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Tidskriftsartikel (refereegranskat)abstract
- Fibrillin-1 (FBN1) is an important constituent of the vascular wall and earlier studies have indicated an effect of the FBN1 2/3 genotype on blood pressure as well as aortic stiffness in men. The aim of the present study was to determine whether the FBN1 2/3 genotype was associated with the presence of carotid plaque and incident cardiovascular morbidity and mortality in middle-aged subjects. The FBN1 genotype was characterized in 5765 subjects (2424 men, 3341 women; age 45-69years) recruited from the Malmo Diet and Cancer Study Cardiovascular Cohort, Sweden. Plaque occurrence and intima-media thickness (IMT) of the carotid artery were assessed by ultrasound. The incidence of first cardiovascular events (myocardial infarction and stroke) and cause-specific mortality were monitored over a mean follow-up period of 13.2years. The most common FBN1 genotypes were 2/2, 2/3 and 2/4, which accounted for 92.2% (n=5317) of subjects. There were no differences between the three genotypes regarding age, blood pressure, glucose, lipids, smoking habits, common carotid artery diameter and intima-media thickness in men and women. The presence of plaque in the carotid artery was higher in men with the 2/3 genotype compared with the 2/2 and 2/4 genotypes (55% vs 46% and 50%, respectively; P=0.007). No similar differences were observed in women. No significant relationship was observed between FBN1 genotypes and the incidence of cardiovascular disease or all-cause mortality. The increased prevalence of plaque in the carotid artery of middle-aged men with the FBN1 2/3 genotype indicates pathological arterial wall remodelling with a more pronounced atherosclerotic burden.
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| 3. |
- Ermund, Anna, et al.
(författare)
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Hypertonic saline releases the attached small intestinal cystic fibrosis mucus.
- 2015
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Ingår i: Clinical and experimental pharmacology & physiology. - : Wiley. - 1440-1681 .- 0305-1870. ; 42:1, s. 69-75
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Tidskriftsartikel (refereegranskat)abstract
- Hypertonic saline inhalation has become a cornerstone in the treatment of cystic fibrosis (CF), but its effect on CF mucus is still not understood. In CF, mucus stagnates in the airways, causing mucus plugging, and forming a substrate for bacterial invasion. Using horizontal Ussing-type chambers to allow easy access to the tissue, we have recently shown that the small intestinal mucus of CF mice is attached to the epithelium and not freely movable as opposed to normal mucus, thus pointing to a similarity between the CF mucus in the ileum and airways. In the same type of system, we investigated how hypertonic saline affects mucus thickness, attachment and penetrability to fluorescent beads the size of bacteria in ileal explants from the cystic fibrosis transmembrane conductance regulator mutant (ΔF508) mouse, in order to characterize how this common therapy affects mucus properties. Hypertonic saline (1.75-5%) detached the mucus from the epithelium, but the mucus remained impenetrable to beads the size of bacteria. This approach might be used to test other mucolytic interventions in CF.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Johansson, Barbro
(författare)
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Hypertension mechanisms causing stroke
- 1999
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Ingår i: Clinical and Experimental Pharmacology and Physiology. - : Wiley. - 1440-1681 .- 0305-1870. ; 26:7, s. 563-565
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Tidskriftsartikel (refereegranskat)abstract
- 1. Although it is well established that hypertension is the main risk factor for stroke, the complexity of cerebrovascular problems related to hypertension is not generally appreciated. 2. Hypertension can cause stroke through many mechanisms. A high intraluminal pressure will lead to extensive alteration in endothelium and smooth muscle function in intracerebral arteries. The increased stress on the endothelium can increase permeability over the blood-brain barrier and local or multifocal brain oedema. Endothelial damage and altered blood cell-endothelium interaction can lead to local thrombi formation and ischaemic lesions. Fibrinoid necrosis can cause lacunar infarcts through focal stenosis and occlusions. Degenerative changes in smooth muscle cells and endothelium predisposes for intracerebral haemorrhages. Furthermore, hypertension accelerates the arteriosclerotic process, thus increasing the likelihood for cerebral lesions related to stenosis and embolism originating from large extracranial vessels, the aortic arch and from the heart. 3. Adaptive structural changes in the resistance vessels, while having the positive effect of reducing the vessel wall tension, have the negative consequence of increased peripheral vascular resistance that may compromise the collateral circulation and enhance the risk for ischaemic events in connection with episodes of hypotension or distal to a stenosis. 4. Hypertension is clearly a risk factor for vascular dementia. All the mechanisms referred to above may be important.
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| 8. |
- Odenlund, Malin, et al.
(författare)
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Stimulation of oestrogen receptor-expressing endothelial cells with oestrogen reduces proliferation of cocultured vascular smooth muscle cells.
- 2008
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Ingår i: Clinical and Experimental Pharmacology and Physiology. - : Wiley. - 1440-1681 .- 0305-1870. ; 35:3, s. 245-248
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Tidskriftsartikel (refereegranskat)abstract
- 1. Oestrogen reduces vascular smooth muscle cell proliferation in mouse vascular injury models. Data on the antiproliferative effect of oestrogen in cultured vascular smooth muscle cells (VSMC) are less conclusive than those obtained in whole animal studies. 2. In the present study, we investigated the hypothesis that oestrogen-induced attenuation of VSMC proliferation is facilitated by the presence of endothelial cells (EC) using a coculture system of EC and VSMC. 3. Treatment with a physiological concentration of oestrogen (17beta-estradiol (E2); 100 nmol/L) had no effect on fetal calf serum (FCS)-stimulated DNA synthesis in either A7r5 VSMC or bEnd.3 EC. However, stimulation of bEnd. 3 cells with E2 in a coculture system of bEnd.3 and A7r5 cells reduced FCS-induced DNA synthesis in A7r5 cells by approximately 45%. The nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (l-NAME; 100 micromol/L) did not reverse the oestrogen-induced attenuation of DNA synthesis. The antiproliferative effect of E2 may be mediated via either oestrogen receptor (ER) alpha, ERbeta or both because the bEnd.3 cells expressed immunoreactivity for both ER subtypes. 4. These data show that ERalpha- and ERbeta-expressing endothelial cells, which are stimulated with a physiological concentration of oestrogen, release a factor(s) that arrests the proliferation of cocultured VSMC. Oestrogen-induced attenuation of vascular smooth muscle cell proliferation is not prevented by L-NAME, suggesting that a mechanism other than endothelial NO is involved.
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| 9. |
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| 10. |
- Ermund, Anna, et al.
(författare)
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OligoG CF-5/20 normalizes cystic fibrosis mucus by chelating calcium.
- 2017
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Ingår i: Clinical and experimental pharmacology & physiology. - : Wiley. - 1440-1681 .- 0305-1870. ; 44:6, s. 639-647
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Tidskriftsartikel (refereegranskat)abstract
- The goal of this study was to determine whether the guluronate (G) rich alginate OligoG CF-5/20 (OligoG) could detach cystic fibrosis (CF) mucus by calcium chelation, which is also required for normal mucin unfolding. Since bicarbonate secretion is impaired in CF, leading to insufficient mucin unfolding and thereby attached mucus and since bicarbonate has the ability to bind calcium, we hypothesized that the calcium chelating property of OligoG would lead to detachment of CF mucus. Indeed, OligoG could compete with the N-terminus of the MUC2 mucin for calcium binding as shown by microscale thermophoresis. Further, effects on mucus thickness and attachment induced by OligoG and other alginate fractions of different length and composition were evaluated in explants of CF mouse ileum mounted in horizontal Ussing-type chambers. OligoG at 1.5% caused effective detachment of CF mucus and the most potent alginate fraction tested, the poly-G fraction of about 12 residues, had similar potency compared to OligoG whereas mannuronate-rich (M) polymers had minimal effect. In conclusion, OligoG binds calcium with appropriate affinity without any overt harmful effect on the tissue and can be exploited for treating mucus stagnation. This article is protected by copyright. All rights reserved.
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