scholarly journals Apolipoprotein and LRP1-Based Peptides as New Therapeutic Tools in Atherosclerosis

2021 ◽  
Vol 10 (16) ◽  
pp. 3571
Author(s):  
Aleyda Benitez Amaro ◽  
Angels Solanelles Curco ◽  
Eduardo Garcia ◽  
Josep Julve ◽  
Jose Rives ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Foam Cell ◽  
Cell Formation ◽  
Experimental Models ◽  
Foam Cell Formation ◽  
Cholesterol Transport ◽  
Mimetic Peptides ◽  
Arterial Intima ◽  
Therapeutic Tools ◽  
Underlying Mechanisms

Apolipoprotein (Apo)-based mimetic peptides have been shown to reduce atherosclerosis. Most of the ApoC-II and ApoE mimetics exert anti-atherosclerotic effects by improving lipid profile. ApoC-II mimetics reverse hypertriglyceridemia and ApoE-based peptides such as Ac-hE18A-NH2 reduce cholesterol and triglyceride (TG) levels in humans. Conversely, other classes of ApoE and ApoA-I mimetic peptides and, more recently, ApoJ and LRP1-based peptides, exhibit several anti-atherosclerotic actions in experimental models without influencing lipoprotein profile. These other mimetic peptides display at least one atheroprotective mechanism such as providing LDL stability against mechanical modification or conferring protection against the action of lipolytic enzymes inducing LDL aggregation in the arterial intima. Other anti-atherosclerotic effects exerted by these peptides also include protection against foam cell formation and inflammation, and induction of reverse cholesterol transport. Although the underlying mechanisms of action are still poorly described, the recent findings suggest that these mimetics could confer atheroprotection by favorably influencing lipoprotein function rather than lipoprotein levels. Despite the promising results obtained with peptide mimetics, the assessment of their stability, atheroprotective efficacy and tissue targeted delivery are issues currently under progress.

scholarly journals C-Terminus apoA-1 mimetic peptides to detect cognate auto-antibodies and reverse HIV-induced foam cell formation

2019 ◽  
Vol 2 (2) ◽  
Author(s):  
Nathalie Satta ◽  
Sabrina Pagano ◽  
Baris Gencer ◽  
Laurent Kaiser ◽  
Oliver Hartley ◽  
...  
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
C Terminus ◽  
Mimetic Peptides

scholarly journals Adenosine A2Areceptor occupancy stimulates expression of proteins involved in reverse cholesterol transport and inhibits foam cell formation in macrophages

2004 ◽  
Vol 76 (3) ◽  
pp. 727-734 ◽  
Author(s):  
Allison B. Reiss ◽  
Mohammad M. Rahman ◽  
Edwin S. L. Chan ◽  
M. Carmen Montesinos ◽  
Nahel W. Awadallah ◽  
...  
Keyword(s):  
Reverse Cholesterol Transport ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Cholesterol Transport

scholarly journals CD36 N-terminal cytoplasmic domain is not required for the internalization of oxidized low-density lipoprotein

2008 ◽  
Vol 28 (3) ◽  
pp. 145-151 ◽  
Author(s):  
Chris McDermott-Roe ◽  
Juliette Martin ◽  
Sophie Collot-Teixeira ◽  
John L. McGregor
Keyword(s):  
Foam Cell ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Cytoplasmic Domain ◽  
Foam Cell Formation ◽  
Low Density ◽  
Hek 293 ◽  
Human Embryonic Kidney Cells ◽  
Arterial Intima

The uptake of OxLDLs (oxidized low density lipoproteins) by CD36-expressing macrophages in the arterial intima and the subsequent ‘foam cell’ formation represents a crucial step in the initiation and development of atherosclerotic plaques. The present study has addressed the function of the CD36 N-terminal cytoplasmic domain in the binding and internalization of OxLDL. A selection of CD36 N-terminal cytoplasmic domain mutants were generated and stably expressed in HEK-293 (human embryonic kidney) cells. The capacity of three mutants [CD36_C3/7-A (CD36-C3A/C7A), CD36_D4/R5-A (CD36-D4A/R5A) and CD36_nCPD− (CD36 lacking the N-terminal cytoplasmic domain)] to bind and endocytose OxLDL was then studied using immunofluorescence microscopy and quantitative fluorimetry. Each of the CD36 constructs was expressed at differing levels at the cell surface, as measured by flow cytometry and Western blotting. Following incubation with DiI (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate)–OxLDL, cells bearing the CD36_wt (wild-type CD36), CD36_C3/7-A, CD36_D4/R5-A and CD36_nCPD− constructs all internalized DiI–OxLDL into endosomal structures, whereas empty-vector-transfected cells failed to do so, indicating that, unlike the C-terminal cytoplasmic domain, the N-terminal cytoplasmic domain is not essential for the endocytosis of OxLDL. In conclusion, the uptake of OxLDL by CD36 is not reliant on the presence of the CD36 N-terminal cytoplasmic domain. However, the N-terminal cytoplasmic domain may conceivably be implicated in the maturation of CD36.

C-terminus apoa-1 mimetic peptides to detect cognate auto-antibodies and reverse HIV-induced foam cell formation

2020 ◽  
Vol 315 ◽  
pp. e125
Author(s):  
N. Satta ◽  
S. Pagano ◽  
B. Gencer ◽  
L. Kaiser ◽  
O. Hartley ◽  
...  
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
C Terminus ◽  
Mimetic Peptides

scholarly journals Infliximab Reverses Suppression of Cholesterol Efflux Proteins by TNF-α: A Possible Mechanism for Modulation of Atherogenesis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Iryna Voloshyna ◽  
Sangeetha Seshadri ◽  
Kamran Anwar ◽  
Michael J. Littlefield ◽  
Elise Belilos ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Cholesterol Transport ◽  
Tnf Α ◽  
Atp Binding Cassette Transporters ◽  
Modified Lipoproteins ◽  
Control Set ◽  
Necrosis Factor

Tumor necrosis factor- (TNF-)αis a proinflammatory proatherogenic cytokine. Infliximab, an anti-TNF-αmonoclonal antibody, is effective in treating rheumatoid arthritis. However, its impact on cardiovascular burden and lipid transport is unclear. The present study investigates the effect of TNF-αand infliximab on reverse cholesterol transport (RCT) proteins. Uptake of modified lipoproteins by macrophages in the vasculature leads to atherogenic foam cell formation. RCT is mediated by proteins including ATP binding cassette transporters A1 (ABCA1), G1 (ABCG1), liver X receptor- (LXR-)α, and 27-hydroxylase. RCT counteracts lipid overload by ridding cells of excess cholesterol. THP-1 human monocytes were incubated with either TNF-αalone or TNF-αwith infliximab. Expression of proteins involved in cholesterol efflux was analyzed. TNF-αsignificantly reduced both ABCA1 and LXR-αmRNA (to68.5±1.59%,P<0.05, and41.2±0.25%,P<0.01, versus control set as 100%, resp.). Infliximab nullified the TNF-αeffect. Results were confirmed by Western blot. Infliximab abolished the increase in foam cells induced by TNF-α. TNF-αtreatment significantly reduces ABCA1 and LXR-αexpression in monocytes, thus bringing about a proatherogenic state. The anti-TNF drug infliximab, commonly used in rheumatology, restored RCT proteins. This is the first report of an atheroprotective effect of infliximab on RCT in monocytes.

scholarly journals Puerarin Inhibits oxLDL-Induced Macrophage Activation and Foam Cell Formation in Human THP1 Macrophage

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Heng Zhang ◽  
Zhenhua Zhai ◽  
Hongyu Zhou ◽  
Yao Li ◽  
Xiaojie Li ◽  
...  
Keyword(s):  
Macrophage Activation ◽  
Foam Cell ◽  
Scientific Evidence ◽  
Scavenger Receptor ◽  
Cell Formation ◽  
Vascular Diseases ◽  
Foam Cell Formation ◽  
Proinflammatory Gene ◽  
Underlying Mechanisms

Puerarin, an isoflavone derived from Kudzu roots, has been widely used for treatment of cardiovascular and cerebral vascular diseases in China and other Asian countries. However, the underlying mechanisms are largely unknown. The present study investigated whether puerarin inhibited atherogenic lipid oxLDL-mediated macrophage activation and foam cell formation in human THP1 macrophage. Treatment with oxLDL significantly increased the mRNA expression of proinflammatory cytokines tumor necrosis factorα(TNFα, 160%) and interleukin (IL) 1β(13 fold) accompanied by upregulation of toll-like receptor 4 (TLR4, 165%) and the ratio of phospho-IκBα/IκBαin THP1 macrophage. Puerarin dose-dependently prevented an increase in oxLDL-induced proinflammatory gene expression with downregulation of TLR4 and the ratio of phospho-IκBα/IκBα. Furthermore, puerarin prevented oxLDL-mediated lipid deposition and foam cell formation associated with downregulation of scavenger receptor CD36. Flow cytometry analysis showed that puerarin reduced the number of early apoptotic cells of macrophages induced by oxLDL. Our results show that puerarin has anti-inflammatory and antiatherogenic effects in vitro; the underlying mechanisms may involve the inhibition of TLR4/NFκB pathway and downregulation of CD36 expression. The results from the present study provide scientific evidence and may expand our armamentarium to use puerarin for prevention and treatment of cardiovascular and atherosclerotic diseases.

scholarly journals Endoplasmic Reticulum Stress in Macrophages: The Vicious Circle of Lipid Accumulation and Pro-Inflammatory Response

Biomedicines ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 210
Author(s):  
Vasily N. Sukhorukov ◽  
Victoria A. Khotina ◽  
Mariam Bagheri Ekta ◽  
Ekaterina A. Ivanova ◽  
Igor A. Sobenin ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Inflammatory Response ◽  
Er Stress ◽  
Lipid Accumulation ◽  
Foam Cell ◽  
Cell Formation ◽  
Cell Types ◽  
Foam Cell Formation ◽  
Human Disorders ◽  
Underlying Mechanisms

The endoplasmic reticulum (ER) stress is an important event in the pathogenesis of different human disorders, including atherosclerosis. ER stress leads to disturbance of cellular homeostasis, apoptosis, and in the case of macrophages, to foam cell formation and pro-inflammatory cytokines production. In atherosclerosis, several cell types can be affected by ER stress, including endothelial cells, vascular smooth muscular cells, and macrophages. Modified low-density lipoproteins (LDL) and cytokines, in turn, can provoke ER stress through different processes. The signaling cascades involved in ER stress initiation are complex and linked to other cellular processes, such as lysosomal biogenesis and functioning, autophagy, mitochondrial homeostasis, and energy production. In this review, we discuss the underlying mechanisms of ER stress formation and the interplay of lipid accumulation and pro-inflammatory response. We will specifically focus on macrophages, which are the key players in maintaining chronic inflammatory milieu in atherosclerotic lesions, and also a major source of lipid-accumulating foam cells.

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