Soluble LOX‐1: A Novel Biomarker in Patients With Coronary Artery Disease, Stroke, and Acute Aortic Dissection?

Hofmann, Anja; Brunßen, Coy; Wolk, Steffen; Reeps, Christian; Morawietz, Henning

doi:10.1161/jaha.119.013803

Cited by 38 publications

(43 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…45,46 Although we could not demonstrate significant changes in blood pressure, lipid profiles, and inflammatory markers, likely due to all values being within a healthy range, HDL cholesterol was slightly increased, consistent with the report by Yang et al 47 Serum levels of oxidative LDL and the soluble form of LOX-1 (lectin-like oxidized low-density lipoprotein [ox-LDL] receptor-1), a dominant receptor that recognizes and internalizes ox-LDL, as biomarkers of vascular oxidative stress, were also not altered by LCMUFA intake or the control oil (data not shown). 48 Therefore, further studies are needed to elucidate whether LCMUFA can improve dyslipidemia in patients.…”

Section: Discussionmentioning

confidence: 99%

Long-chain monounsaturated fatty acids improve endothelial function with altering microbial flora

Tsutsumi

Yamasaki

Takeo

et al. 2021

Translational Research

View full text Add to dashboard Cite

Fish oil-derived long-chain monounsaturated fatty acids (LCMUFAs) with a carbon chain length longer than 18 units ameliorate cardiovascular risk in mice. In this study, we investigated whether LCMUFAs could improve endothelial functions in mice and humans. In a double-blind, randomized, placebo-controlled, parallelgroup, multi-center study, healthy subjects were randomly assigned to either an LCMUFA oil (saury oil) or a control oil (olive and tuna oils) group. Sixty subjects were enrolled and administrated each oil for 4 weeks. For the animal study, ApoE À/À mice were fed a Western diet supplemented with 3% of either gadoleic acid (C20:1) or cetoleic acid (C22:1) for 12 weeks. Participants from the LCMUFA group showed improvements in endothelial function and a lower trimethylamine-N-oxide level, which is a predictor of coronary artery disease. C20:1 and C22:1 oils significantly improved atherosclerotic lesions and plasma levels of several inflammatory cytokines, including IL-6 and TNF-a. These beneficial effects were consistent with an improvement in the gut microbiota environment, as evident from the decreased ratio of Firmicutes and/ or Bacteroidetes, increase in the abundance of Akkermansia, and upregulation of short-chain fatty acid (SCFA)-induced glucagon-like peptide-1 (GLP-1) expression and serum GLP-1 level. These data suggest that LCMUFAs alter the microbiota environment that stimulate the production of SCFAs, resulting in the induction of GLP-1 secretion. Fish oil-derived long-chain monounsaturated fatty acids might thus help to protect against cardiovascular disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Long-chain monounsaturated fatty acids improve endothelial function with altering microbial flora

Tsutsumi

Yamasaki

Takeo

et al. 2021

Translational Research

View full text Add to dashboard Cite

show abstract

“…Despite the still unclear function of sLOX-1 in the circulation there is growing evidence that this receptor fragment might be used as clinical biomarker for the diagnosis of vascular disease including coronary artery disease (CAD), acute coronary syndrome (ACS), ischemic stroke and acute aortic dissection (AAD). The disease associations of sLOX-1 and its potential clinical uses were recently reviewed in a very comprehensive way ( 81 ), why we discuss these aspects here only briefly. As analyzed by classical sandwich ELISAs, in healthy individuals sLOX-1 is present in very low concentrations (few pg/ml).…”

Section: Functions Of Lox-1 Proteolytic Cleavage Fragmentsmentioning

confidence: 99%

Proteolytic Regulation of the Lectin-Like Oxidized Lipoprotein Receptor LOX-1

Mentrup

Cabrera-Cabrera

Schröder

2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

The lectin-like oxidized-LDL (oxLDL) receptor LOX-1, which is broadly expressed in vascular cells, represents a key mediator of endothelial activation and dysfunction in atherosclerotic plaque development. Being a member of the C-type lectin receptor family, LOX-1 can bind different ligands, with oxLDL being the best characterized. LOX-1 mediates oxLDL uptake into vascular cells and by this means can promote foam cell formation. In addition, LOX-1 triggers multiple signaling pathways, which ultimately induce a pro-atherogenic and pro-fibrotic transcriptional program. However, the molecular mechanisms underlying this signal transduction remain incompletely understood. In this regard, proteolysis has recently emerged as a regulatory mechanism of LOX-1 function. Different proteolytic cleavages within the LOX-1 protein can initiate its turnover and control the cellular levels of this receptor. Thereby, cleavage products with individual biological functions and/or medical significance are produced. Ectodomain shedding leads to the release of a soluble form of the receptor (sLOX1) which has been suggested to have diagnostic potential as a biomarker. Removal of the ectodomain leaves behind a membrane-bound N-terminal fragment (NTF), which despite being devoid of the ligand-binding domain is actively involved in signal transduction. Degradation of this LOX-1 NTF, which represents an athero-protective mechanism, critically depends on the aspartyl intramembrane proteases Signal peptide peptidase-like 2a and b (SPPL2a/b). Here, we present an overview of the biology of LOX-1 focusing on how proteolytic cleavages directly modulate the function of this receptor and, what kind of pathophysiological implications this has in cardiovascular disease.

show abstract

“…Some cell receptors related to cell inflammation are increased in stroke patients. Lectin-like oxidized LDL receptor-1 (LOX-1) is a scavenger receptor found in atherosclerotic carotid lesions, the shedding of which is promoted by inflammatory molecules and by oxLDL [85]. The soluble form of LOX-1 (sLOX-1) can be released into the systemic circulation in ruptured atherosclerotic lesions [156] and may serve as an early diagnostic biomarker as in acute coronary syndrome [157].…”

Section: Enzymes Adhesion Molecules and Cell Receptorsmentioning

confidence: 99%

Search for Reliable Circulating Biomarkers to Predict Carotid Plaque Vulnerability

Puig

Jiménez‐Xarrié

Camps‐Renom

et al. 2020

IJMS

View full text Add to dashboard Cite

Atherosclerosis is responsible for 20% of ischemic strokes, and the plaques from the internal carotid artery the most frequently involved. Lipoproteins play a key role in carotid atherosclerosis since lipid accumulation contributes to plaque progression and chronic inflammation, both factors leading to plaque vulnerability. Carotid revascularization to prevent future vascular events is reasonable in some patients with high-grade carotid stenosis. However, the degree of stenosis alone is not sufficient to decide upon the best clinical management in some situations. In this context, it is essential to further characterize plaque vulnerability, according to specific characteristics (lipid-rich core, fibrous cap thinning, intraplaque hemorrhage). Although these features can be partly detected by imaging techniques, identifying carotid plaque vulnerability is still challenging. Therefore, the study of circulating biomarkers could provide adjunctive criteria to predict the risk of atherothrombotic stroke. In this regard, several molecules have been found altered, but reliable biomarkers have not been clearly established yet. The current review discusses the concept of vulnerable carotid plaque, and collects existing information about putative circulating biomarkers, being particularly focused on lipid-related and inflammatory molecules.

show abstract

Soluble LOX‐1: A Novel Biomarker in Patients With Coronary Artery Disease, Stroke, and Acute Aortic Dissection?

Cited by 38 publications

References 79 publications

Long-chain monounsaturated fatty acids improve endothelial function with altering microbial flora

Long-chain monounsaturated fatty acids improve endothelial function with altering microbial flora

Proteolytic Regulation of the Lectin-Like Oxidized Lipoprotein Receptor LOX-1

Search for Reliable Circulating Biomarkers to Predict Carotid Plaque Vulnerability

Contact Info

Product

Resources

About