LOX-1 receptor: A potential link in atherosclerosis and cancer (original) (raw)
Related papers
2006
LOX-1, a lectin-like 52-kD receptor for oxidized low-density lipoproteins (ox-LDL), is present primarily on endothelial cells. This receptor is upregulated by ox-LDL itself and by angiotensin II, endothelin, cytokines, and shear stress, all participants in atherosclerosis. This receptor is upregulated in the arteries of hypertensive, dyslipidemic, and diabetic animals. Upregulation of LOX-1 has been identified in atherosclerotic arteries of several animal species and humans, not only on the endothelial lining, but also in the neovasculature of the atherosclerotic plaque, and this receptor is often co-localized with apoptotic cells. Recent studies show upregulation of LOX-1 in the ischemic-reperfused myocardium. LOX-1 inhibition is associated with attenuation of atherosclerosis and associated ischemic injury. LOX-1 may be a novel, exciting target for drug therapy.
Atherosclerosis, 2011
Objective: Lectin-like oxidized LDL receptor-1 (LOX-1), the endothelial receptor for OxLDL, is believed to be responsible for a number of OxLDL-induced effects in the endothelium. Methods and results: In the present study we showed that LDL modified by 15-lipoxygenase (15LO-LDL), a form of minimally modified lipoprotein, beside its ability to induce pro-inflammatory responses such as oxidative stress and the expression of adhesion molecules, significantly increases LOX-1 expression in endothelial cells, both at transcriptional and at protein level. Such effect is likely to be mediated by p38 MAPK and NF-kB pathways. We then permanently overexpressed LOX-1 in an endothelial cell line and showed that 15LO-LDL were a ligand for LOX-1, and that the interaction LOX-1/15LO-LDL upregulated ICAM-1 surface expression. Conclusion: Altogether these results indicate minimally modified LDL as a new inducer for LOX-1 expression and as a new ligand for LOX-1.
LOX-1 and cancer: an indissoluble liaison
Cancer Gene Therapy
Recently, a strong correlation between metabolic disorders, tumor onset, and progression has been demonstrated, directing new therapeutic strategies on metabolic targets. OLR1 gene encodes the LOX-1 receptor protein, responsible for the recognition, binding, and internalization of ox-LDL. In the past, several studied, aimed to clarify the role of LOX-1 receptor in atherosclerosis, shed light on its role in the stimulation of the expression of adhesion molecules, pro-inflammatory signaling pathways, and pro-angiogenic proteins, including NF-kB and VEGF, in vascular endothelial cells and macrophages. In recent years, LOX-1 upregulation in different tumors evidenced its involvement in cancer onset, progression and metastasis. In this review, we outline the role of LOX-1 in tumor spreading and metastasis, evidencing its function in VEGF induction, HIF-1alpha activation, and MMP-9/MMP-2 expression, pushing up the neoangiogenic and the epithelial–mesenchymal transition process in glioblas...
The role of lectin-like oxidised low-density lipoprotein receptor-1 in vascular pathology
Diabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular Disease, 2014
The lectin-like oxidised low-density lipoprotein receptor-1 (LOX-1) is a vascular scavenger receptor that plays a central role in the pathogenesis of atherothrombotic disease, which remains the main cause of mortality in the Western population. Recent evidence indicates that targeting LOX-1 represents a credible strategy for the management vascular disease and the current review explores the role of this molecule in the diagnosis and treatment of atherosclerosis. LOX-1-mediated pro-atherogenic effects can be inhibited by anti-LOX-1 monoclonal antibodies and procyanidins, whereas downregulation of LOX-1 expression has been achieved by antisense oligonucleotides and a specific pyrrole-imidazole polyamide. Furthermore, LOX-1 can be utilised for plaque imaging using monoclonal antibodies and even the selective delivery of anti-atherosclerotic agents employing immunoliposome techniques. Also, plasma levels of the circulating soluble form of LOX-1 levels are elevated in atherosclerosis an...
LOX-1 in Atherosclerosis and Myocardial Ischemia
Journal of the American College of Cardiology, 2017
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), one of the scavenger receptors for oxidized low-density lipoprotein cholesterol (ox-LDL), plays a crucial role in the uptake of ox-LDL by cells in the arterial wall. Mounting evidence suggests a role for LOX-1 in various steps of the atherosclerotic process, from initiation to plaque destabilization. Studies of the genetic structure of LOX-1 have also uncovered various genetic polymorphisms that could modulate the risk of atherosclerotic cardiovascular events. As evidence supporting the vital role of LOX-1 in atherogenesis keeps accumulating, there is growing interest in LOX-1 as a potential therapeutic target. This review discusses the discovery and genetics of LOX-1; describes existing evidence supporting the role of LOX-1 in atherogenesis and its major complication, myocardial ischemia; and summarizes LOX-1 modulation by some naturally occurring compounds and efforts toward development of small molecules and biologics that could be of therapeutic use.
LOX-1, OxLDL, and Atherosclerosis
Mediators of Inflammation, 2013
Oxidized low-density lipoprotein (OxLDL) contributes to the atherosclerotic plaque formation and progression by several mechanisms, including the induction of endothelial cell activation and dysfunction, macrophage foam cell formation, and smooth muscle cell migration and proliferation. Vascular wall cells express on their surface several scavenger receptors that mediate the cellular effects of OxLDL. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the main OxLDL receptor of endothelial cells, and it is expressed also in macrophages and smooth muscle cells. LOX-1 is almost undetectable under physiological conditions, but it is upregulated following the exposure to several proinflammatory and proatherogenic stimuli and can be detected in animal and human atherosclerotic lesions. The key contribution of LOX-1 to the atherogenic process has been confirmed in animal models; LOX-1 knockout mice exhibit reduced intima thickness and inflammation and increased expression of protective factors; on the contrary, LOX-1 overexpressing mice present an accelerated atherosclerotic lesion formation which is associated with increased inflammation. In humans, LOX-1 gene polymorphisms were associated with increased susceptibility to myocardial infarction. Inhibition of the LOX-1 receptor with chemicals or antisense nucleotides is currently being investigated and represents an emerging approach for controlling OxLDL-LOX-1 mediated proatherogenic effects.
The LOX1 Scavenger Receptor and Atherosclerotic Plaque Rupture
Atherosclerosis is a chronic systemic inflammatory disease; the end-stage of which is plaque rupture. This depends on plaque composition and vulnerability rather than the severity of stenosis . Vulnerable plaques are associated with an intense inflammatory response and a thin fibrous cap . Remodeling and degradation of the extracellular matrix (ECM) and fibrous cap are maintained by the products of inflammatory cells . The lectin-like oxidized low-density lipoprotein scavenger receptor (LOX-1) is an increasing focus of attention for molecular, cellular, and clinical studies. Recent genetic studies have identified a strong link between several single nucleotide polymorphisms on the LOX-1 gene and the risk of acute coronary syndrome (ACS) . We review how the LOX-1 receptor and its ligand, oxidized low-density lipoprotein (oxLDL), are implicated at critical stages of plaque destabilization and rupture.