Abstract:Background
Low-density lipoprotein (LDL) is an important plasma lipoprotein transporting lipids to peripheral tissues/cells. The oxidation of LDL plays critical roles in atherogenesis and its oxidized form (oxLDL) is an important risk factor of atherosclerosis. The biomechanical properties of LDL/oxLDL are closely correlated with the disease. To date, however, the oxidation-induced changes in size and biomechanical properties (stiffness and stickiness) of LDL particles are less investigated.
Methods
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“…Low density lipoprotein (LDL) is a kind of lipoprotein particle that carries cholesterol into peripheral tissue cells and can be oxidized into oxidized LDL [ 38 , 39 ]. There are many unsaturated fatty acids (PUFAs) in the core fatty acids of LDL, accounting for about 35–70% of the total fatty acids of LDL, which are prone to self-oxidation.…”
Long-term sunlight exposure will cause the accumulation of free radicals in the skin and lead to oxidative damage and aging, antioxidant drugs have gradually become the focus of research, but there is little research on antioxidant drugs for percutaneous treatment. The purpose of this study was to prepare ligustrazine hydrochloride (TMPZ)-loaded liposome–hydrogel (TMPZ-LG), evaluate its antioxidant properties, and apply it on the skin of mice to observe whether it had preventive and therapeutic effect on the irradiation under the ultraviolet rays, in an attempt to make it into a new kind of delivery through the skin. TMPZ-LG was prepared by the combination of film dispersion and sodium carboxymethylcellulose (2%, CMC-Na) natural swelling method. The release rates in vitro permeation across the dialysis membrane and ex vivo transdermal had both reached 40%; the scavenging effect of TMPZ-LG on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and H2O2 were 65.57 ± 4.13% and 73.06 ± 5.65%; the inhibition rate of TMPZ-LG on malondialdehyde (MDA) production in liver homogenate and anti-low density lipoprotein (LDL) oxidation experiments ex vivo were 15.03 ± 0.9% and 21.57 ± 1.2%. Compared with untreated mice, the skin pathological symptoms of mice coated with TMPZ-LG were significantly reduced after ultraviolet irradiation, and there was statistical significance. The results showed TMPZ-LG could exert good antioxidant activity in vitro and ex vivo; therefore, it is feasible to prevent and treat skin oxidation.
“…Low density lipoprotein (LDL) is a kind of lipoprotein particle that carries cholesterol into peripheral tissue cells and can be oxidized into oxidized LDL [ 38 , 39 ]. There are many unsaturated fatty acids (PUFAs) in the core fatty acids of LDL, accounting for about 35–70% of the total fatty acids of LDL, which are prone to self-oxidation.…”
Long-term sunlight exposure will cause the accumulation of free radicals in the skin and lead to oxidative damage and aging, antioxidant drugs have gradually become the focus of research, but there is little research on antioxidant drugs for percutaneous treatment. The purpose of this study was to prepare ligustrazine hydrochloride (TMPZ)-loaded liposome–hydrogel (TMPZ-LG), evaluate its antioxidant properties, and apply it on the skin of mice to observe whether it had preventive and therapeutic effect on the irradiation under the ultraviolet rays, in an attempt to make it into a new kind of delivery through the skin. TMPZ-LG was prepared by the combination of film dispersion and sodium carboxymethylcellulose (2%, CMC-Na) natural swelling method. The release rates in vitro permeation across the dialysis membrane and ex vivo transdermal had both reached 40%; the scavenging effect of TMPZ-LG on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and H2O2 were 65.57 ± 4.13% and 73.06 ± 5.65%; the inhibition rate of TMPZ-LG on malondialdehyde (MDA) production in liver homogenate and anti-low density lipoprotein (LDL) oxidation experiments ex vivo were 15.03 ± 0.9% and 21.57 ± 1.2%. Compared with untreated mice, the skin pathological symptoms of mice coated with TMPZ-LG were significantly reduced after ultraviolet irradiation, and there was statistical significance. The results showed TMPZ-LG could exert good antioxidant activity in vitro and ex vivo; therefore, it is feasible to prevent and treat skin oxidation.
“…Previous studies on native and oxidized LDL reported smaller particles and a reduced Young's modulus under acidic conditions compared to neutral environment (Wang et al, 2020(Wang et al, , 2021. The oxidized form of LDL (oxLDL) is a known risk factor in atherosclerosis.…”
Lipoproteins (LPs) are micelle-like structures with a similar size to extracellular vesicles (EVs) and are therefore often co-isolated, as intensively discussed within the EV community. LPs from human blood plasma are of particular interest as they are responsible for the deposition of cholesterol ester and other fats in the artery, causing lesions, and eventually atherosclerosis. Plasma lipoproteins can be divided according to their size, density and composition into chylomicrons (CM), very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Here, we use atomic force microscopy for mechanical characterization of LPs. We show that the nanoindentation approach used for EV analysis can also be used to characterize LPs, revealing specific differences between some of the particles. Comparing LPs with each other, LDL exhibit a higher bending modulus as compared to CM and VLDL, which is likely related to differences in cholesterol and apolipoproteins. Furthermore, CM typically collapse on the surface after indentation and HDL exhibit a very low height after surface adhesion both being indications for the presence of LPs in an EV sample. Our analysis provides new systematic insights into the mechanical characteristics of LPs. K E Y WO R D S atomic force microscopy (AFM), chylomicrons (CM), high-density lipoproteins (HDL), lipoproteins (LPs), low-density lipoproteins (LDL), mechanical properties, very-low-density lipoproteins (VLDL)
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
“…In agreement with previously published works of other groups [ 39 , 40 , 41 , 42 , 43 ], the AFM measurements of HDL particles were adapted for our Atomic Force Microscope (JPK BioAFM—NanoWizard 4, JPK, Berlin, Germany). AFM probes made of silicon nitride with a nominal spring constant of 0.25 N/m and a nominal tip radius between 5 and 8 nm (FASTSCAN-D, Bruker Nano Inc., Camarillo, CA, USA) were used.…”
Lipoprotein particles (LPs) are excellent transporters and have been intensively studied in cardiovascular diseases, especially regarding parameters such as their class distribution and accumulation, site-specific delivery, cellular internalization, and escape from endo/lysosomal compartments. The aim of the present work is the hydrophilic cargo loading of LPs. As an exemplary proof-of-principle showcase, the glucose metabolism-regulating hormone, insulin, was successfully incorporated into high-density lipoprotein (HDL) particles. The incorporation was studied and verified to be successful using Atomic Force Microscopy (AFM) and Fluorescence Microscopy (FM). Single-molecule-sensitive FM together with confocal imaging visualized the membrane interaction of single, insulin-loaded HDL particles and the subsequent cellular translocation of glucose transporter type 4 (Glut4).
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