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- Österberg, Klas, 1966, et al.
(författare)
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Intimal hyperplasia in mouse vein grafts is regulated by flow
- 2005
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Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 42:1, s. 13-20
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Tidskriftsartikel (refereegranskat)abstract
- Altered flow conditions are presumed to cause stenosis in vein grafts due to exaggerated neointimal formation. The aim of this study was to establish a mouse model of flow-regulated intimal hyperplasia (IH) in vein grafts. The caval vein was grafted into the common carotid artery of 38 mice, followed by modulation of the blood flow, resulting in vein grafts with high (HF) and low flow (LF). The vessel wall thickening was evaluated after 3, 14 and 42 days by morphometric analyses and immunohistochemistry. There was an immediate significant change in flow, which was persistent throughout the time of observation. After 42 days, flow was increased 2.7 times in HF animals compared to LF animals. The vessel wall was composed of two layers where the inner layer was positive for alpha-actin and considered as IH. The area of neointimal formation was 74% larger in the LF group compared to the HF group. The present study demonstrates that flow regulates IH in vein grafts in mice. This model gives the potential to study the effect of shear stress on vascular biology in genetically modified animals.
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- Österberg, Klas, 1966
(författare)
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Vascular Wall Responses to Bypass Grafting - Studies in Mice
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abstract Vein grafts are frequently used in bypass surgery for treatment of coronary artery disease and lower limb ischemia. Unfortunately the long-term patency is impaired by vein graft stenoses due to intimal hyperplasia (IH). It is assumed that exaggerated intimal thickening is initiated by vessel wall injuries or local flow disturbances. Accumulation and proliferation of smooth muscle cells (SMCs) are key events in the formation of IH. It has been an established opinion that these cells have their solely origin in the underlying media. This theory has been challenged by recent research, which has demonstrated recruitment of SMCs from other sources than the local vessel wall. Mice models including genetically modified strains have had a major impact on the reformed view upon vascular repair. In this thesis, recruitment pathways of intimal SMCs and the impact of blood flow on vein graft intimal thickening were investigated. A new mouse model, which enables studies of different blood flow through vascular grafts was established. The area of IH in vein grafts was measured in two groups, which had a 2.7 times difference in blood flow. The area was 70% larger in the low flow group compared to high flow, which shows that vein graft IH is regulated by the magnitude of blood flow. Recruitment pathways of SMCs to IH in vein grafts were studied in genetically modified mice, expressing the enzyme LacZ. Thirty percent of the cells originated from sources apart from the grafts. External shielding of the vein grafts resulted in decreased contribution of cells from recipient mice, which point at transadventitial migration as an important recruitment pathway. SMC migration from the adjacent artery could not be detected, which indicate that the connected artery does not play any role for formation of vein graft stenoses. The ability of externally recruited SMCs to regenerate the vessel wall was investigated by implantation of grafts in which cells had been abolished. Acellular vein grafts developed similar degree of IH as cellular vein grafts, which demonstrate that externally recruited SMCs by themselves can form intimal thickening. Acellular arteries were also implanted. The externally recruited SMCs to the arteries had limited ability to regenerate the medial SMC population and no vasomotor function was observed. This demonstrates that recipient derived SMC progenitor cells can contribute to pathological cellular formations, but lack ability to re-establish the normal morphology and function of the arterial wall. In conclusion, the results from this thesis show that the vein wall in response to bypass grafting develops IH, which is regulated by the magnitude of blood flow. The intimal SMCs can be derived from sources outside the vessel wall and may partly be recruited by transadventitial migration but not from the adjacent artery. The SMCs with external origin have ability to contribute to IH but not to the functional population of medial SMCs.
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