ABSTRACT
Accumulation of cholesterol in arterial wall macrophages is a main hallmark of atherosclerosis. The ABCG1 transporter mediates cholesterol efflux to high density lipoproteins (HDL) and plays an important role in macrophage foam cell formation. The goal of our study was to investigate the potential role of ABCG1 in atherosclerosis development in humans. ABCG1 gene expression has been examined in leukocytes, monocytes and monocyte-derived macrophages of patients with atherosclerosis and in the control group. Real time PCR and Western blotting were used to determine ABCG1 mRNA and ABCG1 protein levels. Monocyte ABCG1 mRNA level was inversely correlated with the rate of artery occlusion (r = -0.45, P = 0.016). Patients with 100% artery occlusions had decreased monocyte ABCG1 mRNA levels compared to patients who had smaller plaques and controls (P < 0.05). ABCG1 mRNA (P < 0.001) and ABCG1 protein (P < 0.05) levels in macrophages of patients with coronary artery stenosis were significantly reduced compared to the control group. No significant correlation between the ABCG1 gene expression in mononuclear cells and HDL cholesterol concentration has been found. Our study suggests that decrease in the ABCG1 gene expression in macrophages is associated with atherosclerosis.
Subject(s)
ATP-Binding Cassette Transporters/metabolism , Atherosclerosis/genetics , Coronary Occlusion/genetics , Macrophages/metabolism , Monocytes/metabolism , RNA, Messenger/metabolism , ATP Binding Cassette Transporter, Subfamily G, Member 1 , ATP-Binding Cassette Transporters/genetics , Arteries/metabolism , Arteries/pathology , Atherosclerosis/metabolism , Atherosclerosis/pathology , Biological Transport , Cholesterol, HDL/metabolism , Coronary Occlusion/metabolism , Coronary Occlusion/pathology , Disease Progression , Female , Gene Expression , Humans , Macrophages/pathology , Male , Middle Aged , Monocytes/pathology , RNA, Messenger/geneticsABSTRACT
ABCA1 transporter is known to play important role in the cholesterol transport from peripheral tissues. However its contribution in atherosclerosis development remains not completely understood. Using Real Time PCR, a significant reduction of ABCA1 mRNA level in leukocytes of patients with atherosclerosis was determined when compared with controls. Mean ABCA1 expression levels in leukocytes for the group of patients and for the control group are 0.57 +/- 0.28 and 0.93 +/- 0.14 (p = 0.02). At the same time we detected a significant increase of ABCA1 mRNA level in macrophages of patients when compared with controls. Mean ABCA1 expression levels in macrophages for the group of patients and for the control group are 1.32 +/- 0.10 and 0.90 +/- 0.14 (p = 0.014). In summary, we suggest that expression level of ABCA1 gene may contribute to the development of atherosclerosis.
Subject(s)
ATP-Binding Cassette Transporters/genetics , Atherosclerosis/genetics , Gene Expression , ATP Binding Cassette Transporter 1 , Adult , Female , Humans , Lymphocytes/metabolism , Macrophages/metabolism , Male , Middle AgedABSTRACT
Intimal hyperplasia (IH) appears to rank high amongst plausible causes of reconstructed arteries restenosis. It always occurs in the area of a surgical intervention on a vessel in response to a mechanical lesion. IH is the cause of thrombosis in 15 to 50% of cases following vascular reconstruction during the first year after the operation (with the exception of early thromboses, which are probably caused by an improperly performed interventional technique). Of a wide variety of clinical situations leading to development of IH in the vascular wall, for the purposes of the present review, we singled out the problem concerning the onset and development of this tissue reaction in intervascular anastomoses, which is currently one of the most important issues. Analysing the publications on the problem concerned showed that amongst significantfactors influencing the development of IH in the anastomosis, the investigators single out different parameters of the anastomoses, configuration (either an end-to-end or an end-to-side anastomosis, the use of special inserts and patches within the latter), as well as the use of autologous or synthetic conduits, blanket suture or interrupted suture, peculiarities of local haemodynamics (linear blood flow rate, distribution of parietal fraction forces, zones of stagnation and flow separation), etc. To a certain degree, the published data are rather controversial. There remain many problems, which are either unaddressed as yet, or insufficiently studied, if at all. For instance, while establishing an anastomosis between a bypass graft and an artery, surgeons often resort to endarterectomy. It is not known whether or not this technique would influence the IH pattern in the anastomosis concerned. Neither is it clear whether the high velocity flow exerts a direct damaging action upon the endothelium, whether it promotes the development of IH in the area of the lesion, and if affirmative, then what the mechanisms of this effect really are. Not studied is the role of various types of synthetic fibres and synthetic grafts (except PTFE), various kinds of suture material in the development of IH in the zone of a vascular anastomosis concerned. This of course is far from being a complete list of the challenges requiring further investigation.
