| 1. |
- Albinsson, Sebastian, et al.
(författare)
-
Stretch-dependent smooth muscledifferentiation in theportal vein - role of actin polymerization, calcium signaling and microRNAs.
- 2014
-
Ingår i: Microcirculation. - : Wiley. - 1549-8719 .- 1073-9688. ; 21:3, s. 230-238
-
Forskningsöversikt (refereegranskat)abstract
- The mechanical forces acting onsmooth muscle cells in the vascular wall are known to regulate processes such as vascular remodeling and contractile differentiation. However, investigations to elucidate the underlying mechanisms of mechanotransduction in smooth muscle have been hampered by technical limitations associated with mechanical studies on pressurized small arteries, due primarily to the small amount of available tissue. The murine portal vein is a relatively large vessel showing myogenic tone that in many respects recapitulates the properties of small resistance vessels. Studies on stretched portal veins to elucidate mechanisms of mechanotransduction in the vascular wall have shown that stretch-sensitive regulation of contractile differentiation is mediated via Rho-activation and actin polymerization, while stretch-induced growth is regulated by the MAP-kinase pathway. In this review, we have summarized findings on mechanotransduction in the portal vein with focus on stretch-induced contractile differentiation and the role of calcium, actin polymerization and microRNAs in this response. This article is protected by copyright. All rights reserved.
|
|
| 2. |
- Andersson, Kristina E, et al.
(författare)
-
Dietary oats and modulation of atherogenic pathways.
- 2012
-
Ingår i: Molecular Nutrition and Food Research. - : Wiley. - 1613-4133 .- 1613-4125. ; 56:7, s. 1003-1013
-
Forskningsöversikt (refereegranskat)abstract
- Consumption of oats has long been known to lower plasma total and low-density lipoprotein (LDL) cholesterol levels, an effect usually attributed to the soluble fibers β-glucans. On the basis of this cholesterol-lowering effect, oats are ascribed cardiovascular health-promoting properties. However, besides cholesterol levels, effects of oats on parameters relating to atherosclerosis development have not been extensively investigated. Since oxidation of lipoproteins and inflammation are characteristics of atherosclerosis in addition to lipid accumulation in the vessel wall, micronutrients in oats (phytochemicals) with antioxidative and anti-inflammatory properties may contribute to an atheroprotective action. Here, we summarize evidence on antiatherogenic properties of oats obtained from in vitro assays, animal experiments, and human studies. Possible effects involving anti-inflammatory and antioxidative actions, as well as preservation of endothelial function, are considered in addition to those related to reduction of plasma cholesterol. Since results of in vitro assays with isolated oat components are difficult to compare with effects of whole oats in humans and experimental animals, more observational studies with isolated oat components or fractions of oats are warranted. Also, there is a lack of epidemiological studies focusing on effects of oat intake on the cardiovascular disease panorama.
|
|
| 3. |
- Andersson, Kristina E, et al.
(författare)
-
Diverse effects of oats on cholesterol metabolism in C57BL/6 mice correlate with expression of hepatic bile acid-producing enzymes.
- 2013
-
Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 52:7, s. 1755-1769
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We previously reported that two substrains of C57BL/6 mice respond differently to oats with respect to reduction in plasma cholesterol. Analysis of this difference might offer clues to mechanisms behind the cholesterol-lowering effect of oats. Here, we address the possible roles of hepatic steroid metabolism and the intestinal microbiota in this respect. METHODS: Female C57BL/6 mice were fed an atherogenic diet with oat bran (27 %) or control fibres for 4 weeks. RESULTS: C57BL/6 NCrl mice responded to oat bran with 19 ± 1 % (P < 0.001) lower plasma cholesterol, 40 ± 5 % (P < 0.01) higher excretion of bile acids and increased expression of the bile acid-producing hepatic enzymes CYP7A1 and CYP8B1, but none of these effects were found in C57BL/6JBomTac mice. However, on control diet, C57BL/6JBomTac had tenfold higher expression of CYP7A1 and levels of hepatic cholesterol esters than C57BL/6NCrl mice. Plasma levels of fructosamine indicated improved glycemic control by oat bran in C57BL/6NCrl but not in C57BL/6JBomTac. C57BL/6JBomTac had higher intestinal microbiota diversity, but lower numbers of Enterobacteriaceae, Akkermansia and Bacteroides Fragilis than C57BL/6NCrl mice. Oat bran increased bacterial numbers in both substrains. Microbiota diversity was reduced by oats in C57BL/6JBomTac, but unaffected in C57BL/6NCrl. CONCLUSIONS: Our data do not support a connection between altered microbiota diversity and reduced plasma cholesterol, but the bacterial composition in the intestine may influence the effects of added fibres. The cholesterol-lowering properties of oats involve increased production of bile acids via the classical pathway with up-regulation of CYP7A1 and CYP8B1. Altered cholesterol or bile acid metabolism may interfere with the potential of oats to reduce plasma cholesterol.
|
|
| 4. |
- Andersson, Kristina E, et al.
(författare)
-
Effects of oats on plasma cholesterol and lipoproteins in C57BL/6 mice are substrain specific.
- 2010
-
Ingår i: British Journal of Nutrition. - 1475-2662. ; 103, s. 513-521
-
Tidskriftsartikel (refereegranskat)abstract
- Cholesterol-lowering effects of oats have been demonstrated in both animals and human subjects. However, the crucial properties of oat-containing diets that determine their health effects need to be further investigated to optimise their use. A mouse model would be a valuable tool, but few such studies have been published to date. We investigated the effects of oat bran on plasma cholesterol and lipoproteins in two substrains of C57BL/6 mice. Western diet was made atherogenic by the addition of 0.8 % cholesterol and 0.1 % cholic acid. After 4 weeks on atherogenic diet, total plasma cholesterol had increased from 1.86-2.53 to 3.77-4.40 mmol/l. In C57BL/6NCrl mice, inclusion of 27 and 40 % oat bran reduced total plasma cholesterol by 19 and 24 %, respectively, reduced the shift from HDL to LDL+VLDL and caused increased faecal cholesterol excretion. There was no effect of oat bran on plasma levels of the inflammatory markers fibrinogen, serum amyloid A or TNF-alpha. Contrary to findings in C57BL/6NCrl mice, there was no sustained effect of oat bran (27 or 40 %) on plasma cholesterol in C57BL/6JBomTac mice after 4 weeks of feeding. Thus, C57BL/6NCrl mice fed an atherogenic diet are a good model for studies of physiological effects of oats, whereas a substrain derived from C57BL/6J, raised in a different breeding environment and likely possessing functional genetic differences from C57BL/6N, is considerably less responsive to oats. The present finding that two substrains of mice respond differently to oats is of practical value, but can also help to elucidate mechanisms of the cholesterol-lowering effect of oats.
|
|
| 5. |
- Andersson, Kristina E, et al.
(författare)
-
Oats (Avena sativa) reduce atherogenesis in LDL-receptor-deficient mice.
- 2010
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; Jul 1, s. 93-99
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: The cholesterol-lowering properties of oats, largely ascribed to its contents of soluble fibers, beta-glucans, are well established, whereas effects on atherogenesis are less well elucidated. Oats also contains components with reported antioxidant and anti-inflammatory effects that may affect atherogenesis. In this work we examined effects of oat bran on plasma cholesterol, markers of inflammation, eNOS expression and development of atherosclerosis in LDL-receptor-deficient (LDLr(-/-)) mice. METHODS AND RESULTS: Female LDLr(-/-) mice were fed Western diet+/-oat bran. Two concentrations of oat bran (40 and 27%) were compared regarding effects on plasma lipids. There was a dose-dependent reduction of plasma cholesterol by 42 and 20% with 40 and 27% oat bran, respectively. Both concentrations also lowered plasma triglycerides (by 45 and 33%) and relative levels of plasma LDL+VLDL. The reduction of plasma lipids was accompanied by increased faecal excretion of cholesterol and bile acids. Oat bran (40%) efficiently reduced atherosclerotic lesion area in the descending aorta (-77%) and aortic root (-33%). Plasma levels of fibrinogen and soluble vascular cell adhesion molecule-1 (VCAM-1) were significantly lower, and immunofluorescence of aortic sections revealed a 75% lower expression of VCAM-1 in oat-fed mice. The expression of eNOS protein in the aortic wall was increased in mice fed oat bran. CONCLUSIONS: Oat bran supplemented to a Western diet lowers plasma cholesterol, reduces levels of some inflammatory markers, increases eNOS expression and inhibits atherosclerotic lesion development in LDLr(-/-) mice. It remains to be investigated which components in oats contribute to these effects.
|
|
| 6. |
- Bhattachariya, Anirban, et al.
(författare)
-
Expression of microRNAs is essential for arterial myogenic tone and pressure-induced activation of the PI3-kinase/Akt pathway.
- 2014
-
Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 1755-3245 .- 0008-6363. ; 101:2, s. 288-296
-
Tidskriftsartikel (refereegranskat)abstract
- The myogenic response is the intrinsic ability of small arteries to constrict in response to increased intraluminal pressure. Although microRNAs have been shown to play a role in vascular smooth muscle function, their importance in the regulation of the myogenic response is not known. In this study, we investigate the role of microRNAs in the regulation of myogenic tone by using smooth muscle-specific and tamoxifen-inducible deletion of the endonuclease Dicer in mice.
|
|
| 7. |
- Bhattachariya, Anirban, et al.
(författare)
-
PYK2 selectively mediates signals for growth versus differentiation in response to stretch of spontaneously active vascular smooth muscle.
- 2014
-
Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 2:7
-
Tidskriftsartikel (refereegranskat)abstract
- Stretch of vascular smooth muscle stimulates growth and proliferation as well as contraction and expression of contractile/cytoskeletal proteins, all of which are also regulated by calcium-dependent signals. We studied the role of the calcium- and integrin-activated proline-rich tyrosine kinase 2 (PYK2) in stretch-induced responses of the rat portal vein loaded by a hanging weight ex vivo. PYK2 phosphorylation at Tyr-402 was increased both by a 10-min stretch and by organ culture with load over several days. Protein and DNA synthesis were reduced by the novel PYK2 inhibitor PF-4594755 (0.5-1 μmol/L), while still sensitive to stretch. In 3-day organ culture, PF-4594755 caused maintained myogenic spontaneous activity but did not affect contraction in response to high-K(+) (60 mmol/L) or to α1-adrenergic stimulation by cirazoline. Basal and stretch-induced PYK2 phosphorylation in culture were inhibited by PF-4594755, closely mimicking inhibition of non-voltage-dependent calcium influx by 2-APB (30 μmol/L). In contrast, the L-type calcium channel blocker, nifedipine (1 μmol/L) eliminated stretch-induced but not basal PYK2 phosphorylation. Stretch-induced Akt and ERK1/2 phosphorylation was eliminated by PF-4594755. PYK2 inhibition had no effect on mRNA expression of several smooth muscle markers, and stretch-sensitive SM22α synthesis was preserved. Culture of portal vein with the Ang II inhibitor losartan (1 μmol/L) eliminated stretch sensitivity of PYK2 and Akt phosphorylation, but did not affect mRNA expression of smooth muscle markers. The results suggest that PYK2 signaling functionally distinguishes effects of voltage- and non-voltage-dependent calcium influx. A small-molecule inhibitor of PYK2 reduces growth and DNA synthesis but does not affect contractile differentiation of vascular smooth muscle.
|
|
| 8. |
- Eussen, Simone R. B. M., et al.
(författare)
-
Simultaneous intake of oat bran and atorvastatin reduces their efficacy to lower lipid levels and atherosclerosis in LDLr-/- mice
- 2011
-
Ingår i: Pharmacological Research. - : Elsevier BV. - 1096-1186 .- 1043-6618. ; 64:1, s. 36-43
-
Tidskriftsartikel (refereegranskat)abstract
- The present study aimed to investigate the effects of separate and simultaneous dietary intake of atorvastatin (ATO) and the soluble fiber oat bran on serum and hepatic lipid levels and the degree of atherosclerosis. Ninety female LDL-receptor-deficient (LDLr-/-) mice were fed a Western-type diet containing either low dose (0.0025%), high dose (0.01%) or no ATO, with or without oat bran (27%) (n = 15 per group) for 16 weeks. Both ATO and oat bran were effective in reducing serum total cholesterol levels (low ATO: -5.48, high ATO: -9.12, oat bran: -3.82 mmol/l, compared to control (no ATO/no oat bran), all p < 0.0001). When oat bran was added to a low dose ATO, the cholesterol-lowering effects of this combination were 50% smaller compared to the low dose ATO diet alone (between-group difference: 2.77 mmol/l, p = 0.002), whereas total cholesterol decreased to a similar extent in the groups fed a high dose ATO, with or without oat bran (between-group difference: 1.10 mmol/l, p = 0.21). Serum LDL- and HDL-cholesterol, triglycerides, hepatic lipid levels and atherosclerotic lesion development showed a similar pattern. In conclusion, the efficacy of oat bran and atorvastatin to lower lipid levels and atherosclerosis is reduced after simultaneous intake. We hypothesize that oat bran inhibits the intestinal absorption of atorvastatin, and consequently its cholesterol-lowering effects. The effects are likely dependent on the type of statin and dietary fiber, and on the relative timing of intake of the statin and the dietary fiber. Future studies should focus on these aspects to provide further insight into the exact mechanism of this food-drug interaction. (C) 2011 Elsevier Ltd. All rights reserved.
|
|
| 9. |
- Forte, Amalia, et al.
(författare)
-
Local inhibition of ornithine decarboxylase reduces vascular stenosis in a murine model of carotid injury
- 2013
-
Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 168:4, s. 3370-3380
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Polyamines are organic polycations playing an essential role in cell proliferation and differentiation, as well as in cell contractility, migration and apoptosis. These processes are known to contribute to restenosis, a pathophysiological process often occurring in patients submitted to revascularization procedures. We aimed to test the effect of alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, on vascular cell pathophysiology in vitro and in a rat model of carotid arteriotomy-induced (re) stenosis. Methods: The effect of DFMO on primary rat smooth muscle cells (SMCs) and mouse microvascular bEnd. 3 endothelial cells (ECs) was evaluated through the analysis of DNA synthesis, polyamine concentration, cell viability, cell cycle phase distribution and by RT-PCR targeting cyclins and genes belonging to the polyamine pathway. The effect of DFMO was then evaluated in arteriotomy-injured rat carotids through the analysis of cell proliferation and apoptosis, RT-PCR and immunohistochemical analysis of differential gene expression. Results: DFMO showed a differential effect on SMCs and on ECs, with a marked, sustained anti-proliferative effect of DFMO at 3 and 8 days of treatment on SMCs and a less pronounced, late effect on bEnd. 3 ECs at 8 days of DFMO treatment. DFMO applied perivascularly in pluronic gel at arteriotomy site reduced subsequent cell proliferation and preserved smooth muscle differentiation without affecting the endothelial coverage. Lumen area in DFMO-treated carotids was 49% greater than in control arteries 4 weeks after injury. Conclusions: Our data support the key role of polyamines in restenosis and suggest a novel therapeutic approach for this pathophysiological process. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
|
|
| 10. |
- Forte, Amalia, et al.
(författare)
-
The Polyamine Pathway as a Potential Target for Vascular Diseases: Focus on Restenosis
- 2011
-
Ingår i: Current Vascular Pharmacology. - 1570-1611. ; 9:6, s. 706-714
-
Tidskriftsartikel (refereegranskat)abstract
- Polyamines are organic polycations expressed by all living organisms, which are known to play an essential role in cell proliferation and differentiation. Recent studies revealed their involvement also in cell contractility and migration and in programmed cell death. These processes are known to contribute to restenosis, a pathophysiological process occurring in 10-20% of patients submitted to revascularization procedures. The advent of bare metal stents and of drug-eluting stents has significantly reduced but not eliminated the incidence of restenosis, which thus remains a clinically relevant problem. Despite the potential role of the polyamine pathway as a therapeutic target due to its involvement in proliferation, apoptosis and migration of vascular cells, experimental inhibition of polyamine synthesis and/or uptake has been poorly investigated in animal models of vascular disease. Here we review the current knowledge about molecular mechanisms related to polyamine functions, with particular reference to the role played by polyamines in vascular cell pathophysiology, together with experimental evidence obtained so far in animal models of (re) stenosis. We also evaluate the advantages of different routes of administration of polyamine synthesis/transport inhibitors and polyamine analogue molecules. Increasing knowledge about the molecular mechanisms and functions of polyamines is expected to shed new light on their potential role as a therapeutic target for restenosis reduction.
|
|
