scholarly journals Enhanced Anti-Atherosclerotic Efficacy of pH-Responsively Releasable Ganglioside GM3 Delivered by Reconstituted High-Density Lipoprotein

2021 ◽  
Vol 22 (24) ◽  
pp. 13624
Author(s):  
Tong Rong ◽  
Bo Wei ◽  
Meiying Ao ◽  
Haonan Zhao ◽  
Yuanfang Li ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
Inhibitory Effect ◽  
High Density ◽  
Ph Responsive ◽  
High Concentration ◽  
Ganglioside Gm3 ◽  
In Vivo Experiments

Recently, the atheroprotective role of endogenous GM3 and an atherogenesis-inhibiting effect of exogenous GM3 suggested a possibility of exogenous GM3 being recruited as an anti-atherosclerotic drug. This study seeks to endow exogenous GM3 with atherosclerotic targetability via reconstituted high-density lipoprotein (rHDL), an atherosclerotic targeting drug nanocarrier. Unloaded rHDL, rHDL loaded with exogenous GM3 at a low concentration (GM3L-rHDL), and rHDL carrying GM3 at a relatively high concentration (GM3H-rHDL) were prepared and characterized. The inhibitory effect of GM3-rHDL on lipid deposition in macrophages was confirmed, and GM3-rHDL did not affect the survival of red blood cells. In vivo experiments using ApoE−/− mice fed a high fat diet further confirmed the anti-atherosclerotic efficacy of exogenous GM3 and demonstrated that GM3 packed in HDL nanoparticles (GM3-rHDL) has an enhanced anti-atherosclerotic efficacy and a reduced effective dose of GM3. Then, the macrophage- and atherosclerotic plaque-targeting abilities of GM3-rHD, most likely via the interaction of ApoA-I on GM3-rHDL with its receptors (e.g., SR-B1) on cells, were certified via a microsphere-based method and an aortic fragment-based method, respectively. Moreover, we found that solution acidification enhanced GM3 release from GM3-rHDL nanoparticles, implying the pH-responsive GM3 release when GM3-rHDL enters the acidic atherosclerotic plaques from the neutral blood. The rHDL-mediated atherosclerotic targetability and pH-responsive GM3 release of GM3-rHDL enhanced the anti-atherosclerotic efficacy of exogenous GM3. The development of the GM3-rHDL nanoparticle may help with the application of exogenous GM3 as a clinical drug. Moreover, the data imply that the GM3-rHDL nanoparticle has the potential of being recruited as a drug nanocarrier with atherosclerotic targetability and enhanced anti-atherosclerotic efficacy.

scholarly journals Potensi Hipolipidemik Yogurt dari Isolat Protein Biji Kecipir (Psophocarpus tetragonolobus) pada Tikus Hiperkolesterol dengan Perlakuan Jumlah Pakan

2017 ◽  
Vol 37 (1) ◽  
pp. 1
Author(s):  
Agus Slamet ◽  
Bayu Kanetro
Keyword(s):  
High Density Lipoprotein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Protein Isolate ◽  
High Density ◽  
Winged Bean ◽  
Low Density ◽  
Sprague Dawley ◽  
High Concentration

Protein content of winged bean is almost the same as soybean, but the beany flavor is more poweful than soybean. Therefore the protein of winged bean was isolated prior to use as raw material of yogurt. This research was aimed to determine the potency of  hypocholestrolemic activity of yogurt protein isolate of winged  bean through in vivo bioassay by using Sprague Dawley male rats. The treatments of the research were yogurt feed treatment with concentration of yogurt 0 (standard feed without yogurt as a control), 2, and 4 g yogurt/day as low and high concentration treatment respectively for 4th weeks after hypercholesterol feed  treatment for 1 week. The blood lipid profile of rats, including triglyceride, cholesterol total, High Density Lipoprotein (HDL), Low  Density Lipoprotein (LDL) cholesterol were analysed on the 2nd  and 4th weeks for the yogurt feed treatment while for before  yogurt feed treatment, the evaluation were based on the  adaptation phase and the 1st week for hypercholesterol phase.  The result of this research showed that the blood triglyceride,  cholesterol total, LDL increased, and the blood HDL decreased in hypercholesterol phase before yogurt feed treatment. The potency of hypocholestrolemic of yogurt from protein isolate of winged  bean was shown by the decreasing of blood triglyceride,  cholesterol total, LDL and increasing the HDL cholesterol after the yogurt feed treatment with low and high concentration. That  indicated that yogurt that was made of protein isolate of winged  bean could reduced cholesterol. ABSTRAKBiji kecipir memiliki kadar protein yang hampir sama dengan  kedelai, namun bau langunya lebih tajam daripada kedelai,  sehingga perlu diisolasi proteinnya sebelum digunakan sebagai  bahan baku yogurt. Tujuan penelitian ini adalah menentukan  potensi hipokolesterolemik yogurt isolat proteun biji kecipir  melalui uji biologis in vivo menggunakan tikus jantan Sprague Dawley. Perlakuan penelitian ini adalah perlakuan pakan yogurt  dengan konsentrasi 0 (pakan standar tanpa penambahan yogurt sebagai kontrol), 2, dan 4 g yogurt/hari berturut-turut sebagai  perlakuan konsentrasi rendah dan tinggi selama 4 minggu  perlakuan pakan yogurt sesudah pemberian pakan hiperkolesterol selama 1 minggu. Profil lipida darah tikus meliputi kadar trigliserida, total kolesterol, kolesterol High Density  Lipoprotein (HDL), dan Low Density Lipoprotein (LDL) dianalisis  pada minggu ke 2 dan 4 minggu selama perlakuan pakan yogurt  dan sebelum perlakuan pakan yogurt yaitu pada fase pemeliharaan adaptasi dan 1 minggu pada fase pemeliharan  hiperkolesterol. Hasil penelitian ini menunjukkan bahwa  trigliserida, total kolesterol, dan kolesterol LDL meningkat dan kolesterol HDL menurun selama fase pemberian pakan  hiperkolesterol sebelum perlakuan pakan yogurt. Potensi  hipokolesterol yogurt isolat protein biji kecipir ditunjukkan dengan penurunan trigliserida, total kolesterol, dan kolesterol LDL, serta peningkatan kolesterol HDL sesudah perlakuan pakan yogurt dengan konsentrasi rendah maupun tinggi. Hal tersebut mengindikasikan bahwa yogurt isolat protein biji kecipir mampu menurunkan kolesterol.

scholarly journals Structure and Dynamics of Oxidized Lipoproteins In Vivo: Roles of High-Density Lipoprotein

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 655
Author(s):  
Hiroyuki Itabe ◽  
Naoko Sawada ◽  
Tomohiko Makiyama ◽  
Takashi Obama
Keyword(s):  
Cardiovascular Diseases ◽  
High Density Lipoprotein ◽  
Foam Cell ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
High Density ◽  
Oxidative Modification ◽  
Foam Cell Formation ◽  
Oxidized Lipoproteins

Oxidative modification of lipoproteins is implicated in the occurrence and development of atherosclerotic lesions. Earlier studies have elucidated on the mechanisms of foam cell formation and lipid accumulation in these lesions, which is mediated by scavenger receptor-mediated endocytosis of oxidized low-density lipoprotein (oxLDL). Mounting clinical evidence has supported the involvement of oxLDL in cardiovascular diseases. High-density lipoprotein (HDL) is known as anti-atherogenic; however, recent studies have shown circulating oxidized HDL (oxHDL) is related to cardiovascular diseases. A modified structure of oxLDL, which was increased in the plasma of patients with acute myocardial infarction, was characterized. It had two unique features: (1) a fraction of oxLDL accompanied oxHDL, and (2) apoA1 was heavily modified, while modification of apoB, and the accumulation of oxidized phosphatidylcholine (oxPC) and lysophosphatidylcholine (lysoPC) was less pronounced. When LDL and HDL were present at the same time, oxidized lipoproteins actively interacted with each other, and oxPC and lysoPC were transferred to another lipoprotein particle and enzymatically metabolized rapidly. This brief review provides a novel view on the dynamics of oxLDL and oxHDL in circulation.

Rapid transformation of [3H]cholesteryl ester m rat high-density lipoprotein: in vivo and in vitro studies

Steroids ◽  
1990 ◽  
Vol 55 (7) ◽  
pp. 308-313
Author(s):  
I.J. Goldberg ◽  
R.S. Rosenfeld ◽  
I. Paul ◽  
L.K. Miller ◽  
M.L. Tiell
Keyword(s):  
High Density Lipoprotein ◽  
Cholesteryl Ester ◽  
Density Lipoprotein ◽  
High Density ◽  
In Vitro Studies ◽  
Rapid Transformation
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