Molecular mechanisms of vascular remodelling
Per Hellstrand, Sebastian Albinsson, Anirban Bhattachariya, Karolina Turczyńska
Blood flow through the different vascular beds in the body is driven by the heart and modulated by the local resistance to flow. This resistance is determined by the structure of the blood vessels and by their degree of contraction (“vascular tone”). Both pressure and flow influence vascular tone, and long-standing effects of such stimuli result in structural alterations of the blood vessels, termed “remodelling”. This may increase vascular resistance, which causes excessive load on the heart and can lead to serious cardiovascular complications. The project aims to investigate the mechanisms behind the remodelling phenomenon.
Pressure within a blood vessel stretches its wall, which stimulates growth processes to normalize the mechanical stress in the tissue. Stretch of the vascular smooth muscle activates growth-stimulating pathways and also causes increased filament organization of the intracellular “cytoskeleton”, composed primarily of the protein actin. This in turn stimulates synthesis of proteins associated with the cytoskeleton and the contractile system. Endothelial cells sense shear stress from the flow of blood, which causes them to release vasodilating substances, such as nitric oxide (NO). This reduces vascular tone but, if pressure is maintained, also increases mechanical stress on the muscle layer, which activates the remodelling process. Current efforts are directed towards elucidating the basic mechanisms by which mechanical stress in the tissue is transmitted to the cytoskeleton and also to clarify the role of the calcium ion in the process. Calcium activates muscle contraction and affects many other cellular processes. Its release into the cytoplasm as well as its elimination occurs by several different routes, which may have specific roles in the regulation of gene expression and may eventually be targeted for prevention or reversal of harmful vascular remodelling.
Health beneficial effects of oats in vascular disease.
Kristina Andersson, Per Hellstrand
Elevated plasma cholesterol is an important risk factor for development of atherosclerosis. Even though efficient lipid-lowering drugs are available, intake of functional foods is an approach that does not require medication and can be widely used in preventive health care to improve public health. The cholesterol-lowering properties of oats are well documented, and are mostly ascribed to its contents of soluble dietary fibres, β-glucans. It is however insufficiently known what chemical properties of the β-glucans are crucial for their cholesterol-reducing capacity. We collaborate with food chemists to elucidate how alterations of molecular weight, structure and protein/carbohydrate interactions affect the cholesterol-reducing capacity of the β-glucans. Oats also contains other potentially bioactive phytochemical components, such as vitamin E, phenolic compounds and flavonoids, that could contribute to reduced atherosclerosis via anti-inflammatory and anti-oxidative effects. We evaluate the contribution of different components in oats to reduced risk of atherosclerosis. The physiological actions of oat components are studied in mouse models where effects on plasma lipids, cholesterol and bile acid excretion, inflammation markers and atherosclerosis are evaluated. The results will be used to form a rational basis for development of new oat products with improved health properties.
EU-project – SmArt (SMall ARTery remodelling)
Per Hellstrand, Ina Nordström, Anirban Bhattachariya and Karolina Turczynska
SmArt is a Marie Curie Initial Training Network (ITN) on SMall ARTery remodelling, funded by the European Commission (website: http://www.smallartery.eu). The network consists of 9 academic groups and one industrial from 7 European countries specialized in the biology of vascular cells and their surrounding extracellular matrix (ECM). 13 early stage researchers (ESR) are supported for 3 years and 1 experienced researcher (ER) for 2 years. The network is coordinated from Lund University by Professor Per Hellstrand. Project manager is Ina Nordström.
The primary scientific objective of the SmArt network is to determine the molecular mechanisms of cell-matrix and cell-cell interactions in small artery remodeling, aiming to aid in the development of new therapies. The following key areas are in focus: 1) Signalling mechanisms in endothelial and smooth muscle cells, 2) Structural and functional rearrangements in the vessel wall, 3) Role of recruited cells in remodelling
Two ESRs at Lund University are supervised by Per Hellstrand. Their projects are focused on the influences of pressure, flow and active tone on signal mechanisms involved in vascular remodelling.
Effects of polyamine synthesis inhibition on vascular smooth muscle cell proliferation and cell cycle progression.
Bengt-Olof Nilsson (PI), Per Hellstrand and Ina Nordström
Polyamines have been shown to regulate cancer cell growth and proliferation but their mechanism of action is not fully understood. Arginine is the common precursor for polyamine and NO formation and thus polyamine and NO synthesis compete for arginine as substate. Elevated polyamine levels enhance vascular smooth muscle cell proliferation promoting vascular smooth muscle cell proliferation, while elevated NO formation, e.g. by causing vasodilatation, is regarded to be beneficial for cardiovascular function and health. In this project we investigate the effects of polyamine synthesis inhibitors and their mechanism of action on vascular smooth muscle cell proliferation and cell cycle progression using a variety of techniques and approaches. Inhibition of polyamine formation may be a way to prevent unwanted vascular smooth muscle cell proliferation as observed in atherosclerosis and restenosis.
Identification of estrogen target genes in vascular and periodontal tissues
Bengt-Olof Nilsson (PI), Gunilla Bratthall, Daniel Jönsson, Daniel Nebel, Marie-Louise Lydrup
Post-menopausal women, lacking endogenous estrogen production, have a higher incidence of cardiovascular and periodontal disease than pre-menopausal women, suggesting that estrogen withdrawal aggravates these serious conditions. Development of atherosclerosis as well as periodontitis is associated with inflammation suggesting inflammation as a common denominator in the pathogenesis. The mechanism for the beneficial effect of estrogen has not been identified. In this project we investigate estrogen receptor distribution and expression in vascular smooth muscle and endothelial cells and in human periodontal ligament cells. Gene array and PCR and ELISA and Western blotting are used to study effects of estrogen on mRNA and protein levels, respectively. Identification of estrogen target genes in vascular and periodontal cells is of primary importance to understand the physiological and pathophysiological role of estrogen. Much of our interest is focused on inflammatory associated genes since we have identified a group of lipopolysaccharide (LPS) responsive genes which are down-regulated by estrogen treatment.
Page Manager: Anna Appelberg
Last modified: 2012-01-11
