The ATP-binding cassette transporter A1 (ABCA1) facilitates the efflux of cholesterol and phospholipids to lipid-free apolipoprotein A1 and small dense high-density lipoproteins. Various studies... Show moreThe ATP-binding cassette transporter A1 (ABCA1) facilitates the efflux of cholesterol and phospholipids to lipid-free apolipoprotein A1 and small dense high-density lipoproteins. Various studies have shown that leukocyte ABCA1 is an anti-atherogenic factor. Dietary cholesterol lowering stabilizes atherosclerotic lesions, however the role of ABCA1 in this process is unknown. Therefore, this study aims to investigate the effect of leukocyte ABCA1 on diet-induced atherosclerotic lesions after withdrawal of the atherogenic diet. Leukocyte ABCA1 was studied by transplanting bone marrow cells from donor mice that were either knock-out (ABCA1-/-) or wild-type for ABCA1 or that overexpressed ABCA1 (ABCA1Tg) into low-density lipoprotein receptor knock-out (LDLr-/-) mice. All three groups of chimeric mice were fed a Western-type diet (WTD: 0.25%cholesterol, 15Êcao butter) for 6 weeks to induce atherosclerotic lesion development. After this period, a baseline group was sacrificed (ABCA1-/- >LDLr-/- n=12; wild-type >LDLr-/- n=14; ABCA1Tg >LDLr-/- n=9) for lesion assessment. The remainder of chimeric mice was switched to a chow diet (low fat, no added cholesterol) for 3 weeks to lower plasma cholesterol levels (ABCA1-/- >LDLr-/- n=14; wild-type >LDLr-/- n=14; ABCA1Tg >LDLr-/- n=12).Withdrawal of the atherogenic diet normalized plasma cholesterol levels in all three groups. As a result, lesion development was stabilized in both the wild-type >LDLr-/- and ABCA1Tg >LDLr-/- mice, however not in the ABCA1-/- >LDLr-/- mice, which displayed a 1.5-fold increase (p<0.01) in atherosclerotic lesion size. Leukocyte ABCA1 is required to halt atherosclerotic lesion progression after dietary cholesterol lowering. Overexpression of ABCA1 did not result in any additional beneficial effects. Show less
The aim of this thesis was to evaluate the safety, feasibility and potential efficacy of autologous bone marrow mononuclear cell injection in patients with chronic ischemic heart disease. For this... Show moreThe aim of this thesis was to evaluate the safety, feasibility and potential efficacy of autologous bone marrow mononuclear cell injection in patients with chronic ischemic heart disease. For this purpose, 30-100 million autologous bone marrow cells were injected into the ischemically-damaged myocardium of 50 patients with chronic ischemic heart disease. The results of the current studies demonstrate that intramyocardial injection of autologous bone marrow mononuclear cells in patients with chronic ischemic heart disease is feasible and safe. In particular, the electrophysiological properties of the injected myocardium remain unchanged and aggravation of coronary atherosclerosis is not observed. Moreover, autologous bone marrow cell injection seems to be associated with a beneficial effect on anginal symptoms, myocardial perfusion and left ventricular (systolic and diastolic) function. The beneficial effects of cardiac cell therapy appear to be sustained over a longer period of follow-up. Show less
