Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 (LOX-1): A Potential Therapeutic Target in Ischemic Stroke

Abstract

Stroke, the leading cause of disability and the second leading cause of death worldwide, is characterized by high morbidity and disability. The lectin-like oxidized low-density lipoprotein receptor (LOX-1) is a scavenger receptor that promotes endothelial dysfunction by recognizing and internalizing oxidized low-density lipoproteins (ox-LDL) to induce the formation, development, and instability of atherosclerotic plaques, ultimately leading to vascular thrombosis. Previous clinical and epidemiological studies have indicated that LOX-1 plays a vital role in cerebral ischemic injury following ischemic stroke. Multiple clinical studies have shown that the genetic polymorphisms in LOX-1 are associated with susceptibility to ischemic stroke. Soluble LOX-1 (sLOX-1), a biomarker of ischemic stroke, is associated with the prognosis of ischemic stroke. This article discusses the clinical and experimental findings on LOX-1 in ischemic stroke and the development of new therapeutic strategies targeting LOX-1.

Keywords: Cerebral ischemia; LOX-1; Stroke; sLOX-1.

Fig. 1

Structure and selective splicing of human OLR1 gene

Fig. 2

Stress factors in the acute phase and ligand binding regulate LOX-1 expression. a Regulation at the transcriptional level. NF-κB and AP1 transcription complexes bind to the promoter recognition region in the LOX-1 gene, promoting LOX-1 gene transcription. b Regulation at the post-transcriptional level. miR-24, miR-98, miR-155, miR-590-5p, miR-186-5p, and miR-let-7 g regulate the translation process of LOX-1 mRNA. c Regulation at the epigenetic level. The methyl groups aid in regulating LOX-1 expression within the promoter region of the LOX-1 gene. Green represents CpG islands, while yellow represents methylation. d Glycosylation modification post-translation. LOX-1, lectin-like oxidized low-density lipoprotein receptor

Fig. 3

LOX-1 participates in vascular endothelial injury. a LOX-1 mediates endothelial dysfunction through inflammation. b L5 binding to LOX-1 mediates platelet aggregation and adhesion between platelets and endothelial cells. c LOX-1 inhibits NO release and vasodilation through oxidative stress. d LOX-1 mediates endothelial-mesenchymal transformation and reduces NO release by inhibiting autophagy. e LOX-1 mediates endothelial apoptosis through caspase 3, caspase 9, and MMP. LOX-1, lectin-like oxidized low-density lipoprotein receptor; MMP, matrix metalloproteinases; NO, nitric oxide

Fig. 4

LOX-1 participates in nerve damage. LOX-1 is involved in neuronal apoptosis and blood–brain barrier damage. LOX-1, lectin-like oxidized low-density lipoprotein receptor