Notably, inhibition of miR-33 by a subcutaneously delivered 2′F/MOE-modified antimiR for 4 weeks in hyperlipidemic low-density lipoprotein receptor (Ldlr−/−) knockout mice fed a standard chow diet enhanced reverse cholesterol transport and showed atherosclerotic plaque regression, consistent with accumulation of the antimiR-33 in plaque macrophages (Rayner et al, 2011a).
The anti-atherogenic properties of HDL are mainly related to reverse cholesterol transport, stabilization of atherosclerotic plaque, and anti-inflammatory and anti-oxidant effects [ 1, 3].
Subsequently, anterograde axonal transport delivers Abeta to plaques (Lazarov et al. 2002; Stokin et al. 2005).
We explored the possibility that downregulation of proteins involved in reverse cholesterol transport away from atheromatous plaques contributes to increased atherogenesis associated with COX inhibition.
Additionally, any approach promoting the transport of excess cholesterol from plaque macrophages back to the liver via plasma high-density lipoprotein (HDL) for biliary and final fecal excretion is expected to prevent atherosclerosis, a mechanistic concept called reverse cholesterol transport (RCT) (Cuchel and Rader, 2006; Degoma and Rader, 2011; Rader and Daugherty, 2008).
This finding suggests that amyloid plaque disrupts the transport of vitamin C into mitochondria via altered Glut1 and induce extracellular oxidative damage that cannot be blocked by insufficient levels of vitamin C. The structure of mitochondria features a double-membrane construction involving an outer and an inner membrane.
Early on, potential anti-atherogenic effects of HDL were mainly attributed to its function in macrophage RCT, i.e. the removal of excess cholesterol from lipid-laden macrophage foam cells in the atherosclerotic plaque and its transport to the liver for excretion in the bile (Rader, 2006; Ross & Glomset, 1973).
Similarly, the low frequency of FOXP3+ Treg in the adventitia could be the result of plaque derived lipoproteins, transported via Vasa vasorum microvessels to the adventitia.
The fact that fructose is characteristically enhanced in the CSF of MS patients irrespective of the presence of active plaques suggests enhanced transport across the brain-CSF barrier, while decreased fructose uptake by blood seems less likely.
This study revealed that cholesterol removal from atherosclerotic plaques requires active transport of HDL through lymphatic endothelial cells, which is mediated by SR-BI.
