Role of LOX-1 (Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1) as a Cardiovascular Risk Predictor

Abstract

Atherosclerosis, the underlying cause of cardiovascular disease (CVD), is a worldwide cause of morbidity and mortality. Reducing ApoB-containing lipoproteins—chiefly, LDL (low-density lipoprotein)—has been the main strategy for reducing CVD risk. Although supported by large randomized clinical trials, the persistence of residual cardiovascular risk after effective LDL reduction has sparked an intense search for other novel CVD biomarkers and therapeutic targets. Recently, Lox-1 (lectin-type oxidized LDL receptor 1), an innate immune scavenger receptor, has emerged as a promising target for early diagnosis and CV risk prediction and is also being considered as a treatment target. Lox-1 was first described as a 50 kDa transmembrane protein in endothelial cells responsible for oxLDL (oxidized LDL) recognition, triggering downstream pathways that intensify atherosclerosis via endothelial dysfunction, oxLDL uptake, and apoptosis. Lox-1 is also expressed in platelets, where it enhances platelet activation, adhesion to endothelial cells, and ADP-mediated aggregation, thereby favoring thrombus formation. Lox-1 was also identified in cardiomyocytes, where it was implicated in the development of cardiac fibrosis and myocyte apoptosis, the main determinants of cardiac recovery following an ischemic insult. Together, these findings have revealed that Lox-1 is implicated in all the main steps of atherosclerosis and has encouraged the development of immunoassays for measurement of sLox-1 (serum levels of soluble Lox-1) to be used as a potential CVD biomarker. Finally, the recent development of synthetic Lox-1 inhibitors and neutralizing antibodies with promising results in animal models has made Lox-1 a target for drug development. In this review, we discuss the main findings regarding the role of Lox-1 in the development, diagnosis, and therapeutic strategies for CVD prevention and treatment.

Non-stenotic Carotid Plaques in Embolic Stroke of Unknown Source

“…The identification of an ipsilateral non-stenotic carotid plaque with or without high-risk features is not sufficient to reclassify ESUS as stroke due to large vessel disease. Further research is, therefore, needed to determine whether combination of vascular imaging findings, clinical data, and candidate biomarkers of plaque progression/instability or atheroembolism ( 46 – 82 ) into multiparameter scores could improve the ability to (1) establish a causal link between ESUS and a non-stenotic carotid plaque, (2) predict plaque progression or stroke recurrence, and (3) select patients who might benefit from adjuvant anti-inflammatory and lipid-lowering therapies as briefly discussed in the next section. Some biomarkers of plaque progression and instability that warrant further investigation specifically in patients with ESUS are presented in Table 3 .…”

Glycation Markers in the Geriatrics Patients

“…The analysis revealed also that SR-BI correlates with one more parameter -Lectin-type oxidized LDL receptor 1 (LOX-1). In the latest publications (2020 and 2021), LOX-1 is presented as a promising target for early diagnosis and cardiovascular risk prediction [39][40][41]. Such enthusiastic announcements made us expect to nd higher levels of LOX-1 in people with stroke, after a myocardial infarction or with obesity, but no such association was found in our geriatric population.…”

Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Level is Related to Clinical Prognosis In Patients with Acute Atherosclerosis-related Ischemic Stroke

“… 21 , 23 , 24 In the field of cardiovascular, it is well-known that sLOX-1 levels can reveal the severity of acute coronary syndrome and is related to the prognosis of coronary artery disease. 20 , 24 In the research of cerebrovascular disease, sLOX-1 levels were elevated in patients with ischemic stroke and transient ischemic attack, 26 – 28 and the elevated were more significantly in severe patients compared to the mild stroke group. 28 Which was confirmed in our study further, we found the proportion of severe neurological deficit at admission in patients with the low level of sLOX-1 was10.14%, much lower than the other 2 groups (21.74% for moderate level of sLOX-1 group and 28.99% for the high level of sLOX-1group).…”