Synthetic dimyristoylphosphatidylcholine liposomes assimilating into high-density lipoprotein promote regression of atherosclerotic lesions in cholesterol-fed rabbits

Abstract

We have reported recently that enrichment of high-density lipoprotein (HDL) with phosphatidylcholine (PC) liposomes is effective in solubilizing cholesterol from isolated human atherosclerotic plaques. In the present study, we investigated the in vivo effect of enrichment of HDL with PC on regression of diet-induced atherosclerosis in rabbits. As part of the study, a preliminary in vitro study on blood collected from the cholesterol-fed rabbits was performed to assess the capacity of the HDL density (d > 1.063 g/mL) plasma fraction from cholesterol-fed rabbits to assimilate multilamellar liposomes of synthetic dimyristoylphosphatidylcholine (DMPC). This was compared with the capacities of egg- and soy-PC liposomes to be assimilated into the HDL density plasma fraction. The capacity of the HDL density fraction to absorb PC from DMPC liposomes (11.5 mg/mL) was more than 10 times greater than egg or soy liposomes. Therefore, DMPC liposomes were chosen to infuse into cholesterol-fed rabbits. Cholesterol-fed rabbits infused weekly with DMPC liposomes (300 mg/kg body weight) for five weeks had significantly decreased aortic cholesterol contents (P < 0.05) compared with saline-infused cholesterol-fed controls. Atherosclerotic plaque volume, as measured by a type of new magnetic resonance imaging analysis, also decreased significantly (P < 0.05) after DMPC treatment. The present findings suggest that the enrichment of HDL with PC via intravenous infusion of synthetic DMPC liposomes could be a potential therapeutic approach for atherosclerotic plaque regression.

In vivo efficacy of HDL-like nanolipid particles containing multivalent peptide mimetics of apolipoprotein A-I

“…PBS controls. There are some previous indications that DMPC can reduce the development of atherosclerosis in vivo ( 62,63 ). In view of these data, it is possible that the lipid component of the nanoparticles is contributing somewhat to the observed atheroprotective effects.…”

Regression of coronary atherosclerosis: Current evidence and future perspectives

“…Nanoparticles can be used for site-targeted delivery of therapeutic agents, including local administration of statins at very high doses that would be toxic if administered systematically [69], and for synthesis of HDLs that result in significant reduction of atherosclerosis in experimental models [70]. While these approaches appear promising for individualizing therapeutics, they still need to be tested in the setting of clinical trials.…”

Ocena wiedzy studentów farmacji w zakresie profilaktyki chorób układu krążenia. Część 1. Wiedza w zakresie prewencji pierwotnej

“…Stężenie cholesterolu LDL w surowicy krwi, utrzymujące się na wysokim poziomie, nasila procesy zapalne w blaszce miażdżycowej, natomiast obniżenie poziomu cholesterolu we wczesnych fazach zmian może powodować ich zahamowanie, a nawet cofanie się [9]. W redukcji poziomu cholesterolu w blaszkach miażdżycowych znaczącą rolę odgrywają lipoproteiny frakcji HDL (high density lipoprotein) [10]. Dane pochodzące z literatury dowodzą, że niskie stężenie cholesterolu frakcji HDL w surowicy krwi jest istotnym czynnikiem ryzyka wystąpienia ChNS [11].…”