Pitavastatin decreases serum LOX-1 ligand levels and MT1-MMP expression in CD14-positive mononuclear cells in hypercholesterolemic patients

Uzui, Hiroyasu; Hayashi, Hideki; Nakae, Izuru; Matsumoto, Tetsuya; Uenishi, Hiroaki; Hayasaki, Hisae; Asaji, Takayoshi; Matsui, Shinobu; Miwa, Kunihisa; Lee, Jong–Dae; Tada, Hiroshi; Sawamura, Tatsuya; Fujita, Masatoshi

doi:10.1016/j.ijcard.2014.07.213

Cited by 7 publications

(2 citation statements)

References 9 publications

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“…A recent APO-E -null mouse model of atherosclerosis found that simvastatin administration reduced CD36 expression as well as atherosclerosis and inflammatory signalling compared with controls [ 114 ]. Statins have been shown to downregulate LOX-1 levels and reduce serum sLOX-1 levels, thus reducing the cellular capacity to sense oxLDL, and activate proatherogenic signalling to downstream pathways [ 115 , 116 ]. Reduced LOX-1 levels caused by statin therapy also has additional anti-atherogenic properties, such as increased NO levels, and downregulation of adhesion molecules [ 117 , 118 ].…”

Section: Srs As Therapeutic Targets In Cvdmentioning

confidence: 99%

Scavenger Receptors as Biomarkers and Therapeutic Targets in Cardiovascular Disease

Cuthbert

Shaik

Harrison

et al. 2020

Cells

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The process of atherosclerosis leads to the formation of plaques in the arterial wall, resulting in a decreased blood supply to tissues and organs and its sequelae: morbidity and mortality. A class of membrane-bound proteins termed scavenger receptors (SRs) are closely linked to the initiation and progression of atherosclerosis. Increasing interest in understanding SR structure and function has led to the idea that these proteins could provide new routes for cardiovascular disease diagnosis, management, and treatment. In this review, we consider the main classes of SRs that are implicated in arterial disease. We consider how our understanding of SR-mediated recognition of diverse ligands, including modified lipid particles, lipids, and carbohydrates, has enabled us to better target SR-linked functionality in disease. We also link clinical studies on vascular disease to our current understanding of SR biology and highlight potential areas that are relevant to cardiovascular disease management and therapy.

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Section: Srs As Therapeutic Targets In Cvdmentioning

confidence: 99%

Scavenger Receptors as Biomarkers and Therapeutic Targets in Cardiovascular Disease

Cuthbert

Shaik

Harrison

et al. 2020

Cells

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“…Levels of sEng and MMP-14 were found to be increased simultaneously in both hyperglycemia and hypoglycemia models and this effect could be reversed with the anti-diabetic drug glucagon-like peptide-1 (GLP-1) ( 25 ). In addition, levels of MMP-14 were significantly decreased after 6 months of therapy with pitavastatin, a drug used to decrease cholesterol levels ( 26 ).…”

Section: Introductionmentioning

confidence: 99%

Monoclonal anti-endoglin antibody TRC105 (carotuximab) prevents hypercholesterolemia and hyperglycemia-induced endothelial dysfunction in human aortic endothelial cells

et al. 2022

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Endoglin (Eng) is a co-receptor of the transforming growth factor β superfamily playing an important role in endothelial dysfunction. TRC105 (carotuximab) is a monoclonal antibody that blocks Eng and its downstream Smad signaling pathway. Here we have investigated for the first time the effects of TRC105 treatment on the development of endothelial dysfunction induced by 7-ketocholesterol (7K) or high glucose (HG), focusing on Eng expression, signaling, and function. In the hypercholesterolemia study, human aortic endothelial cells (HAoECs) were treated with TRC105 (300 μg/ml) for 1 h, followed by the addition of 7K (10 μg/ml) for another 12 h. In the hyperglycemia study, HAoECs were exposed to HG (45 mM) for 60 h, followed by the addition of TRC105 for another 12 h, and cells treated with 5mM glucose and 40 mM mannitol served as control. Protein levels, adhesion, and transmigration of monocytes were assessed by flow cytometry, mRNA expression was measured by qRT-PCR. 7K and HG treatment increased protein levels of NF-κB and Eng and adhesion and transmigration of monocytes through HAoECs monolayer. TRC105 pretreatment reduced the 7K- or HG-induced Eng protein levels and pSmad1/5 and pSmad2/3 signaling. Despite increased protein levels of P-selectin and VCAM-1, TRC105 mediated blockage of Eng prevented 7K- and HG-induced adhesion and transmigration of monocytes through endothelial monolayers. These results suggest that TRC105-mediated Eng blockage can counteract the hypercholesterolemia- and hyperglycemia-induced endothelial dysfunction in HAoECs, suggesting that Eng might be a potential therapeutic target in disorders associated with elevated cholesterol and glucose levels.

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Pitavastatin for lowering lipids

Adams

Alaeiilkhchi

Wright

2020

Cochrane Database of Systematic Reviews

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Pitavastatin decreases serum LOX-1 ligand levels and MT1-MMP expression in CD14-positive mononuclear cells in hypercholesterolemic patients

Cited by 7 publications

References 9 publications

Scavenger Receptors as Biomarkers and Therapeutic Targets in Cardiovascular Disease

Scavenger Receptors as Biomarkers and Therapeutic Targets in Cardiovascular Disease

Monoclonal anti-endoglin antibody TRC105 (carotuximab) prevents hypercholesterolemia and hyperglycemia-induced endothelial dysfunction in human aortic endothelial cells

Pitavastatin for lowering lipids

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