Increased Levels of Lectin‐Like Oxidized Low‐Density Lipoprotein Receptor‐1 in Ischemic Stroke and Transient Ischemic Attack

Abstract

BackgroundSoluble lectin‐like oxidized low‐density lipoprotein receptor‐1 (sLOX‐1) has been shown to be increased in patients with acute ischemic stroke. Here, we evaluated plasma sLOX‐1 levels and vascular carotid plaque LOX‐1 (ie, OLR1) gene expression in patients with ischemic stroke and transient ischemic attack (TIA) with particular focus on their relation to time since symptom onset.Methods and ResultsPlasma sLOX‐1 (n=232) and carotid plaque OLR1 gene expression (n=146) were evaluated in patients who were referred to evaluation for carotid endarterectomy, as well as in healthy control plasma (n=81). Patients were categorized according to presence of acute ischemic stroke or transient ischemic attack (n=35) ≤7 days, >7 days ≤3 months (n=90), >3 months (n=40), or no reported symptoms before study inclusion (n=67). Our major findings were the following: (1) Patients with carotid atherosclerosis had increased plasma sLOX‐1 levels as compared with controls. (2) Plaque OLR1 mRNA levels were increased in carotid plaques (n=146) compared with nonatherosclerotic vessels (ie, common iliac arteries of organ donors, n=10). (3) There were no differences in sLOX plasma levels or OLR1 gene expression when analyzed according to the time since relevant cerebral ischemic symptoms. (4) Also patients with severe carotid atherosclerosis without any previous ischemic events had raised sLOX‐1 levels. (5) Immunostaining showed colocalization between LOX‐1 and macrophages within the carotid plaques. (6) Also patients with acute stroke (within 7 days) caused by atrial fibrillation (n=22) had comparable raised sLOX‐1 levels.Conclusions sLOX‐1 levels are elevated in patients with ischemic stroke and transient ischemic attack independent of cause and time since the ischemic event.

Targeting LOX‐1 in atherosclerosis and vasculopathy: current knowledge and future perspectives

“…Importantly, LOX‐1 has a positive correlation with thrombolysis in myocardial infarction score and heart failure. In agreement with these findings, sLOX‐1 levels and LOX‐1 gene expression are elevated in carotid atherosclerotic plaques from human patients with ischemic stroke . Hence, circulating sLOX‐1 could be a useful biomarker to predict major cardiovascular events, as well as used for screening of high‐risk individuals and the management of ACS patients .…”

“…LOX‐1 also inhibits macrophage migration and promotes foam cell formation induced by various proatherogenic treatments . A recent study has shown that LOX‐1 colocalizes with macrophages in human carotid plaques, indicating the potential role of LOX‐1 in regulating foam cell formation and plaque vulnerability in atherosclerosis development in humans.…”

“…Under stressful conditions, such as acute myocardial ischemia, sLOX‐1 is released into the circulatory system and thus can be detected in the conditioned media and serum. Therefore, sLOX‐1 is considered to be a potentially useful biomarker for evaluating the severity and risk of atherosclerosis and associated diseases, including acute coronary syndrome (ACS), rheumatoid arthritis, pre‐eclampsia, ischemic stroke, and obesity . sLOX‐1 in the coronary circulation shows higher sensitivity and specificity in the diagnosis and prediction of ACS than traditional biomarkers such as troponin T and high sensitivity CRP (hs‐CRP), two well‐established biomarkers for the diagnosis and prediction for ACS .…”

COVID‐19—Associated dyslipidemia: Implications for mechanism of impaired resolution and novel therapeutic approaches

“…73 The serum-soluble form of LOX-1 (sLOX-1), the extracellular portion of LOX-1 produced by proteolytic shedding of the receptor, reflects membrane-bound intact receptor levels and is elevated in acute coronary syndrome (ACS), 74 stable coronary artery disease 75 and stroke. 76 The association of LOX-1 activation and acute inflammatory conditions raises the possibility that LOX-1 is also activated and may contribute to COVID-19 complications. In fact, recent clinical data suggest that SARS-CoV-2 may cause a pediatric multisystem inflammatory syndrome reminiscent of Kawasaki Disease (KD) in children.…”

LOX-1: A potential driver of cardiovascular risk in SLE patients

“…Recently, inflammatory HDL from SLE patients was shown to reduce the nuclear co-localization of ATF3, an anti-inflammatory transcription factor, through the LOX-1 receptor, making primary human monocyte-derived macrophages prone to inflammatory cytokine secretion [24]. In human disease, elevated levels of cleaved soluble LOX-1 (sLOX-1) have been reported in patients with acute coronary syndrome [25,26], systolic heart failure [27], ischemic stroke [28], and psoriasis [29].…”