Abstract
Purpose: Nanomicelles (NMs) have been widely used for various biomedical applications due to its unique physiochemical properties. The present study aims to investigate the effects of vascular cell adhesion molecule-1 (VCAM-1)-targeted and peroxisome proliferator-activated receptor δ (PPARδ) agonist (GW0742)-loaded NMs on apoptosis and migration in oxidized low-density lipoprotein (ox-LDL)-induced human aortic vascular smooth muscle cells (HAVSMCs).Methods: The GW0742-loaded NMs (M-GW) and VCAM-1-targeted NMs loaded with GW0742 (TM-GW) were prepared, and then the morphologies and the size distribution of M-GM and TM-GM were observed by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. In vitro drug release assay of M-GM and TM-GM were performed as well. Next, HAVSMCs were cultured in medium containing ox-LDL to mimic atherosclerotic environment, and the effects of free GW0742, M-GM and TM-GM on endocytosis, cell migration and apoptosis, as well as the expression of VCAM-1, and proteins associated with migration and apoptosis were measured in HAVSMCs treated with ox-LDL.Results: M-GM and TM-GM were successfully prepared. VCAM-1 was overexpressed in HAVSMCs treated with ox-LDL, and TM-GM had a strong targeting ability to HAVSMCs treated with ox-LDL compared with M-GM. In addition, compared with free GW0742, both M-GM and TM-GM significantly diminished cell apoptosis and migration in HAVSMCs treated with ox-LDL.Conclusions: TM-GM had a superior suppressing effect on apoptosis and migration of ox-LDL-induced HAVSMCs.
Highlights
As a chronic progressive inflammatory disease, atherosclerosis is one of the most important types of arteriosclerotic vascular diseases, characterized by subendothelial lipoprotein retention and endothelial injury in the arterial wall [1,2]
Cumulative drug release profiles revealed that both Methods: The GW0742-loaded NMs (M-GW) and targeted NMs loaded with GW0742 (TM-GW) exhibited a burst release of GW0742 within 5 h and a slow release from 5 to 24 h at pH 7.4 and 5.0 (Figure 1C)
In the present study, we investigated the effect of peroxisome proliferator-activated receptor δ (PPARδ) agonist GW0742 on oxidized low-density lipoprotein (ox-LDL)-induced human aortic vascular smooth muscle cell (HAVSMC)
Summary
As a chronic progressive inflammatory disease, atherosclerosis is one of the most important types of arteriosclerotic vascular diseases, characterized by subendothelial lipoprotein retention and endothelial injury in the arterial wall [1,2]. Atherosclerosis is usually responsible for various cardiac–cerebral vascular disease and peripheral vascular disease, with high rates of disability and mortality [1,3]. The drug treatments for atherosclerosis have the intensive progress, unsatisfactory adverse effects such as liver injury and myopathy still exist [4]. It is essential to search for novel treatment methods of atherosclerosis. The initial inflammatory damage of endothelial cells leads to the permeability of lipid-increasing proteins and the adhesion of leukocytes, and adhere leukocytes to swallow oxidized low-density lipoprotein (ox-LDL)
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