UNASSIGNED: Cardiovascular disease that is caused by atherosclerosis is the leading cause of death worldwide. Atherosclerosis is primarily triggered by endothelial dysfunction and the accumulation of modified low-density lipoprotein (LDL) particles in the subendothelial space of blood vessels. Early reports have associated oxidized LDL with altered fibrinolysis and atherogenesis. It has been suggested that myeloperoxidase oxidized LDL (Mox-LDL) is involved in atherosclerosis because of its significant pathophysiological role in the modification of LDL in vivo. It has been equally demonstrated that Mox-LDL binds to the lectin-like oxidized low-density lipoprotein receptor-1 (lox-1) scavenger receptor which leads to the upregulation of inflammatory mediators in endothelial cells and the progression of cardiovascular disease. It has been also shown that neuroserpin, a member of the serine proteinase inhibitor (serpin) superfamily, has an important role at the level of fibrinolysis in the nervous tissue.
UNASSIGNED: Since little is known about the effects of Mox-LDL on endothelial cell fibrinolytic activity and the involvement of lox-1 in this process, our study aimed at evaluating the in vitro effects of Mox-LDL on neuroserpin release from human aortic endothelial cells (HAECs) and the role of lox-1 scavenger receptor in this context by relying on lox-1 gene silencing in HAECs, culturing the cells in the presence of Mox-LDL, measuring their neuroserpin expression and release by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively, and assessing their fibrinolytic activity using the Euglobulin Clot Lysis Time (ECLT) method.
UNASSIGNED: Our data show that Mox-LDL decreases endothelial cell fibrinolytic capacity by upregulating neuroserpin in lox-1 knockdown cells.
UNASSIGNED: Lox-1 protects the endothelial cells from a Mox-LDL-induced decrease in pro-fibrinolytic capacity, which has important consequences in the context of stroke.

OBJECTIVE: Aspergillus fumigatus (A. fumigatus) keratitis is a type of infectious corneal disease that significantly impairs vision. The objective of this study is to evaluate the therapeutic potential of chelerythrine (CHE) on A. fumigatus keratitis.
METHODS: The antifungal activity of CHE was assessed through various tests including the minimum inhibitory concentration test, scanning electron microscopy, transmission electron microscopy, propidium iodide uptake test and plate count. Neutrophil infiltration and activity were assessed using immunofluorescence staining and the myeloperoxidase test. RT-PCR, western blotting assay, and ELISA were performed to measure the expression levels of proinflammatory cytokines (IL-1β and IL-6), NF-E2-related factor (Nrf2), heme oxygenase-1 (HO-1), and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), as well as to determine the ratio of phosphorylated-p38 (p-p38) mitogen-activated protein kinase (MAPK) to p38 MAPK.
RESULTS: In vitro, CHE inhibited the growth of A. fumigatus conidia, reduced fungal hyphae survival, and prevented fungal biofilm formation. In vivo, CHE reduced the severity of A. fumigatus keratitis and exhibited an excellent anti-inflammatory effect by blocking neutrophil infiltration. Furthermore, CHE decreased the expression levels of proinflammatory cytokines and LOX-1 at both mRNA and protein levels, while also decreasing the p-p38 MAPK/p38 MAPK ratio. Additionally, CHE increased the expression levels of Nrf2 and HO-1.
CONCLUSIONS: CHE provides protection against A. fumigatus keratitis through multiple mechanisms, including reducing fungal survival, inducing anti-inflammatory effects, enhancing Nrf2 and HO-1 expression, and suppressing the signaling pathway of LOX-1/p38 MAPK.

Inflammation and oxidative stress are both considered to be factors in the etiopathogenesis of schizophrenia. LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) and ox-LDL (oxidized low-density lipoprotein) have been reported to be active in neuroinflammation pathways in which they are involved in oxidative stress and inflammation. However, its relationship with schizophrenia is unclear. This study aimed to assess the potential connection between serum ox-LDL and LOX-1 levels in schizophrenia patients, their unaffected first-degree relatives, and healthy controls. The study comprised 63 schizophrenia patients, 57 first-degree relatives, and 63 healthy controls who were age, gender, and BMI-matched. Serum ox-LDL and LOX-1 levels were measured. PANSS was used to assess the severity of the disease. Levels of both ox-LDL and LOX-1 were markedly elevated in individuals diagnosed with schizophrenia when compared to both their relatives and a control group. While ox-LDL levels were significantly higher in relatives of patients compared to controls, there was no significant difference between relatives of patients and control groups for LOX-1 levels. Significant correlations were observed between PANNS general and total and ox-LDL levels and PANNS negative and LOX-1 levels. The relationship between ox-LDL and LOX-1 and schizophrenia is quite limited in the literature and is a new field of study. Future studies are needed to evaluate their role in etiopathogenesis.

Preeclampsia is a hypertensive disorder of pregnancy marked by vascular dysfunction, large artery stiffness, and excess oxidized low-density lipoprotein (oxLDL). oxLDL activates oxidative stress pathways which contribute to arterial stiffness through interaction with the lectin-like oxLDL receptor 1 (LOX-1). Increased vascular stiffness is associated with higher pulse wave velocity and downstream microvasculature damage. Here we evaluated the ability of LOX-1 inhibition (LOX-1i) to prevent large artery structural and microvascular structural and functional changes via assessment of the descending thoracic aorta (DTAo) and posterior cerebral arteries (PCA) in a high cholesterol model of preeclampsia. Adult female Sprague Dawley normal late-pregnant (LP) and experimentally preeclamptic (ePE, high cholesterol diet d7-19) animals underwent intraperitoneal (i.p.) implantation of a mini-osmotic pump at d12 containing LOX-1 neutralizing antibodies (ePE + LOX-1i, n = 7) or goat IgG as vehicle control (LP + IgG, n = 8 and ePE + IgG, n = 8). Animals were studied at d19. DTAos and PCAs were removed for histologic assessment and isolated vessel experiments, respectively. Fetuses and placentas were weighed individually. Plasma was analyzed for markers of oxidative stress. ePE + IgG DTAo elastin content (an indirect metric of stiffness) was not significantly different from the LP + IgG group. Nonetheless, trending elastin break and sinuosity data (higher number of breaks and lower sinuosity in the ePE + IgG group compared to LP + IgG) suggested increased stiffness in this high cholesterol PE model. LOX-1i appeared to prevent a decrease in elastin. PCAs showed no structural changes with ePE or LOX-1i. ePE PCAs had increased reactivity to the nitric oxide donor sodium nitroprusside and decreased tone that was unaffected by LOX-1i. ePE animals had increased plasma oxLDL and 3-nitrotyrosine that was unaffected by LOX-1i. Taken together, LOX-1i may improve large artery stiffness without mitigation of the oxidative stress or cerebral microvascular dysfunction seen in ePE. Understanding these mechanisms is important in abating the long-term risks of preeclampsia.

LOX-1, ORL-1, or lectin-like oxidized low-density lipoprotein receptor 1 is a transmembrane glycoprotein that binds and internalizes ox-LDL in foam cells. LOX-1 is the main receptor for oxidized low-density lipoproteins (ox-LDL). The LDL comes from food intake and circulates through the bloodstream. LOX-1 belongs to scavenger receptors (SR), which are associated with various cardiovascular diseases. The most important and severe of these is the formation of atherosclerotic plaques in the intimal layer of the endothelium. These plaques can evolve into complicated thrombi with the participation of fibroblasts, activated platelets, apoptotic muscle cells, and macrophages transformed into foam cells. This process causes changes in vascular endothelial homeostasis, leading to partial or total obstruction in the lumen of blood vessels. This obstruction can result in oxygen deprivation to the heart. Recently, LOX-1 has been involved in other pathologies, such as obesity and diabetes mellitus. However, the development of atherosclerosis has been the most relevant due to its relationship with cerebrovascular accidents and heart attacks. In this review, we will summarize findings related to the physiologic and pathophysiological processes of LOX-1 to support the detection, diagnosis, and prevention of those diseases.

Atherosclerosis is a complex condition that involves the accumulation of lipids and subsequent plaque formation in the arterial intima. There are various stimuli, cellular receptors, and pathways involved in this process, but oxidative modifications of low-density lipoprotein (ox-LDL) are particularly important in the onset and progression of atherosclerosis. Ox-LDLs promote foam-cell formation, activate proinflammatory pathways, and induce smooth-muscle-cell migration, apoptosis, and cell death. One of the major receptors for ox-LDL is LOX-1, which is upregulated in several cardiovascular diseases, including atherosclerosis. LOX-1 activation in endothelial cells promotes endothelial dysfunction and induces pro-atherogenic signaling, leading to plaque formation. The binding of ox-LDLs to LOX-1 increases the generation of reactive oxygen species (ROS), which can induce LOX-1 expression and oxidize LDLs, contributing to ox-LDL generation and further upregulating LOX-1 expression. This creates a vicious circle that is amplified in pathological conditions characterized by high plasma levels of LDLs. Although LOX-1 has harmful effects, the clinical significance of inhibiting this protein remains unclear. Further studies both in vitro and in vivo are needed to determine whether LOX-1 inhibition could be a potential therapeutic target to counteract the atherosclerotic process.

To investigate the anti-inflammatory and antifungal effects of plumbagin (PL) in Aspergillus fumigatus (A. fumigatus) keratitis, the minimum inhibitory concentration (MIC), time-killing curve, spore adhesion, crystal violet staining, calcium fluoride white staining, and Propidium Iodide (PI) staining were employed to assess the antifungal activity of PL in vitro against A. fumigatus. The cytotoxicity of PL was assessed using the Cell Counting Kit-8 (CCK8). The impact of PL on the expression of HMGB1, LOX-1, TNF-α, IL-1β, IL-6, IL-10 and ROS in A. fumigatus keratitis was investigated using RT-PCR, ELISA, Western blot, and Reactive oxygen species (ROS) assay. The therapeutic efficacy of PL against A. fumigatus keratitis was assessed through clinical scoring, plate counting, Immunofluorescence and Hematoxylin-Eosin (HE) staining. Finally, we found that PL inhibited the growth, spore adhesion, and biofilm formation of A. fumigatus and disrupted the integrity of its cell membrane and cell wall. PL decreased IL-6, TNF-α, and IL-1β levels while increasing IL-10 expression in fungi-infected mice corneas and peritoneal macrophages. Additionally, PL significantly attenuated the HMGB1/LOX-1 pathway while reversing the promoting effect of Boxb (an HMGB1 agonist) on HMGB1/LOX-1. Moreover, PL decreased the level of ROS. In vivo, clinical scores, neutrophil recruitment, and fungal burden were all significantly reduced in infected corneas treated with PL. In summary, the inflammatory process can be inhibited by PL through the regulation of the HMGB-1/LOX-1 pathway. Simultaneously, PL can exert antifungal effects by limiting fungal spore adhesion and biofilm formation, as well as causing destruction of cell membranes and walls.

Lipids play an important role in varying vital cellular processes including cell growth and division. Elevated levels of low-density lipoprotein (LDL) and oxidized-LDL (ox-LDL), and overexpression of the corresponding receptors including LDL receptor (LDLR), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), and cluster of differentiation 36 (CD36), have shown strong correlations with different facets of carcinogenesis including proliferation, invasion, and angiogenesis. Furthermore, a high serum level of LOX-1 is considered as a poor prognostic factor in many types of cancer including colorectal cancer. Ox-LDL could contribute to cancer progression and metastasis through endothelial-to-mesenchymal transition (EMT) and autophagy. Thus, many studies have shed light on the significant role of ox-LDL as a potential therapeutic target for cancer therapy. In various repurposing approaches, anti-dyslipidemia agents, phytochemicals, autophagy modulators as well as recently developed ldl-like nanoparticles have been investigated as potential tumor therapeutic agents by targeting oxidized-LDL/LOX-1 pathways. Herein, we reviewed the role of oxidized-LDL and LOX-1 in cancer progression, invasion, metastasis, and also cancer-associated angiogenesis. Moreover, we addressed therapeutic utility of several compounds that proved to be capable of targeting the metabolic moieties in cancer. This review provides insights on the potential impact of targeting LDL and ox-LDL in cancer therapy and their future biomedical implementations.

OBJECTIVE: Diabetic osteoporosis (DOP) is the most common secondary form of osteoporosis. Diabetes mellitus affects bone metabolism; however, the underlying pathophysiological mechanisms remain unclear. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression is upregulated in conditions characterized by vascular injury, such as atherosclerosis, hypertension, and diabetes. Additionally, Notch, HIF-1α, and VEGF are involved in angiogenesis and bone formation. Therefore, we aimed to investigate the expression of Notch, HIF-1α, and VEGF in the LOX-1 silencing state.
METHODS: Rat bone H-type vascular endothelial cells (THVECs) were isolated and cultured in vitro. Cell identification was performed using immunofluorescent co-expression of CD31 and Emcn. Lentiviral silencing vector (LV-LOX-1) targeting LOX-1 was constructed using genetic recombination technology and transfected into the cells. The experimental groups included the following: NC group, HG group, LV-LOX-1 group, LV-CON group, HG + LV-LOX-1 group, HG + LV-CON group, HG + LV-LOX-1 + FLI-06 group, HG + LV-CON + FLI-06 group, HG + LV-LOX-1 + LW6 group, and HG + LV-CON + LW6 group. The levels of LOX-1, Notch, Hif-1α, and VEGF were detected using PCR and WB techniques to investigate whether the expression of LOX-1 under high glucose conditions has a regulatory effect on downstream molecules at the gene and protein levels, as well as the specific molecular mechanisms involved.
RESULTS: High glucose (HG) conditions led to a significant increase in LOX-1 expression, leading to inhibition of angiogenesis, whereas silencing LOX-1 can reverse this phenomenon. Further analysis reveals that changes in LOX-1 will promote changes in Notch/HIF-1α and VEGF. Moreover, Notch mediates the activation of HIF-1α and VEGF.
CONCLUSIONS: The activation of LOX-1 and the inhibition of Notch/HIF-1α/VEGF in THVECs are the main causes of DOP. These findings contribute to our understanding of the pathogenesis of DOP and offer a novel approach for preventing and treating osteoporosis.

BACKGROUND: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is known as a major receptor for oxidized low-density lipoproteins (oxLDL) and plays a significant role in the genesis of atherosclerosis. Recent research has shown its involvement in cancer, ischemic stroke, and diabetes. LOX-1 is a C-type lectin receptor and is involved in the activation of immune cells and inflammatory processes. It may further interact with pathogens, suggesting a role in infections or the host\'s response.
CONCLUSIONS: This review compiles the current knowledge of potential implications of LOX-1 in inflammatory processes and in host-pathogen interactions with a particular emphasis on its regulatory role in immune responses. Also discussed are genomic and structural variations found in LOX-1 homologs across different species as well as potential involvements of LOX-1 in inflammatory processes from the angle of different cell types and organ-specific interactions.
CONCLUSIONS: The results presented reveal both similar and different structures in human and murine LOX-1 and provide clues as to the possible origins of different modes of interaction. These descriptions raise concerns about the suitability, particularly of mouse models, that are often used in the analysis of its functionality in humans. Further research should also aim to better understand the mostly unknown binding and interaction mechanisms between LOX-1 and different pathogens. This pursuit will not only enhance our understanding of LOX-1 involvement in inflammatory processes but also identify potential targets for immunomodulatory approaches.