Effect of Dexamethasone Palmitate-Low Density Lipoprotein Complex on Cholesterol Ester Accumulation in Aorta of Atherogenic Model Mice.

Abstract

In order to confirm the efficacy of dexamethasone palmitate (DP)-low density lipoprotein (LDL) complex on experimental atherosclerosis in vivo, we examined whether DP-LDL complex could be effective for cholesterol ester accumulation in the aorta of atherogenic mice. Nonatherogenic and atherogenic mice were fed with normal and atherogenic diet for 14 weeks, respectively. Dexamethasone (DEX), lipid emulsion containing DP (DP-LE), or DP-LDL complex was intravenously injected once a week from 8 to 14 weeks. Cholesterol levels in serum and aorta in the atherogenic mice were significantly higher than those of nonatherogenic mice. Injection of DP-LDL complex significantly reduced cholesterol ester (CE) accumulation in the aorta of atherogenic mice. The reduction of CE accumulation in aorta treated with DP-LDL complexes was 10 and 100 times more potent than that with DP-LE and DEX, respectively. The radioactivity in the aorta of atherogenic mice treated with 3 H-DP-LDL complex was significantly higher than that with 3 H-DP-LE and 3 H-DEX at 24 h after injection. Even 7 d after injection, a significant amount of radioactivity was present only in the aorta of atherogenic mice treated with DP-LDL complex. This result suggests that DP-LDL complex is selectively delivered to the atherogenic lesions in the aorta of atherogenic mice, and then DP released from the complex inhibits CE accumulation in the aortic intima. Therefore, DP-LDL complex may be a good drug-carrier in drug delivery system for atherosclerosis.

Carotid intima media thickness is increased and associated with morning cortisol in subjects with non-functioning adrenal incidentaloma

“…It has been shown that exogenous glucocorticoids are associated with impaired cholinergic vasodilatation via disturbances in endothelial nitric oxide system [28]. However, it must be noted that studies in animals have shown the atheroprotective effects of medium-term glucocorticoid receptor agonist therapy in mice [29] and rabbits [30]. The data regarding cardiovascular risk in both Cushing Syndrome and sCS emphasized the role of metabolic disturbances [5,31,32].…”

Intra-vascular glucocorticoid metabolism as a modulator of vascular structure and function

“…Further, the systemic effects of glucocorticoids on cardiovascular risk factors (glucose, insulin, lipids and blood pressure) may offset beneficial effects within the vessel wall. Dexamethasone reduces cholesterol ester accumulation in the aorta [133], and glucocorticoids (dexamethasone, hydrocortisone) inhibit neointimal lesion formation in rats [134,135], rabbits [136][137][138] and dogs [139] (with a few contradictory reports [140,141]). Clinical trials in humans, by contrast, have proved disappointing (with notable exceptions [130]): methylprednisolone did not inhibit restenosis after coronary angioplasty [142] or stent implantation [143], whilst the combination of a glucocor-570 P. W. F. Hadoke et al Intra-vascular glucocorticoid metabolism ticoid with colchicine increased the risk of coronary aneurysm following stent placement [144].…”

A Novel Liposomal Dexamethasone Palmitate Formulation and Anti‐inflammatory Effects on Mice

“…[1][2][3][4] Because of its insolubility in water and thus relatively low bioavailability by oral administration, research on the drug delivery system of dexamethasone palmitate has raised many interests. Liposomes, closed bilayer vesicles with around 100 nm in diameter, formed by the distribution of lipid and cholesterol in water, have a positive effect on body's drug absorption because of their similarity and compatibility with cell membrane.…”