LOX-1, Oxidative Stress and Inflammation: A Novel Mechanism for Diabetic Cardiovascular Complications

Yan, Meiling; Mehta, Jawahar L.; Zhang, Weifang; Hu, Chong

doi:10.1007/s10557-011-6342-4

Cited by 61 publications

(37 citation statements)

References 92 publications

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“…Whether other mechanisms contribute to the increased LOX-1 expression is yet to be further investigated. Serum sLOX-1 levels are elevated in many inflammatory diseases (Hayashida et al, 2005;Lubrano et al, 2008;Yan et al, 2011;Takanabe-Mori et al, 2013). Its clinical importance is gradually increasing as a potential biomarker of various inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

“…LOX-1 was mainly expressed by endothelial cells (ECs) and later found also to be inducibly expressed by vascular smooth muscle cells (VSMCs), macrophages, and platelets (Zhao et al, 2011). Recent studies have verified that LOX-1 activation is involved in the inflammatory process and inflammatory-related disorders (Hayashida et al, 2005;Lubrano et al, 2008;Yan et al, 2011;Takanabe-Mori et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Serum sLOX-1 Levels Are Correlated with the Presence and Severity of Obstructive Sleep Apnea

Li²,

Wu³

et al. 2015

Genetic Testing and Molecular Biomarkers

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Context: Inflammation plays a critical role in the development and progression of obstructive sleep apnea (OSA). Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) activation is involved in the pathophysiology of inflammatory process-related disorders. Objective: This study aims to investigate whether serum soluble LOX-1 (sLOX-1) levels are associated with the presence and severity of OSA. Materials and Methods: A total of 137 OSA patients and 78 controls were recruited in this study. Serum sLOX-1 levels were measured by enzyme-linked immunosorbent assay. The severity of OSA was assessed by the apnea-hypopnea index (AHI). Results: OSA patients had significantly higher serum sLOX-1 levels compared with controls. Serum sLOX-1 levels elevated with the increment of OSA severity. sLOX-1 was the independent predictor of OSA. Serum sLOX-1 levels were significantly correlated with AHI and high-sensitivity C-reactive protein levels. Conclusions: Serum sLOX-1 levels were independently correlated with the presence and severity of OSA. These findings revealed that sLOX-1 might function as a potential biomarker for monitoring the development and progression of OSA.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum sLOX-1 Levels Are Correlated with the Presence and Severity of Obstructive Sleep Apnea

Li²,

Wu³

et al. 2015

Genetic Testing and Molecular Biomarkers

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“…Inflammation adversely affects insulin sensitivity and worsens diabetic retinopathies, neuropathies, and vasculopathies (4-6). Proinflammatory cytokines produced by macrophages, such as tumor necrosis factor-a (TNF-a) and interleukin 1 (IL-1), create a vicious cycle of reduced insulin sensitivity (3,(7)(8)(9).To the present, more than 300 clinical trials of mesenchymal stem/stromal cell (MSC) transplantations have been conducted worldwide with a wide clinical application targeting more than 50 indications (www.clinicaltrials.gov). Systemic transplantation is the most favorable route for MSC delivery from a safety and systemic regulation point of view, and 56% of MSC clinical trials are allogenic transplantation (10).…”

mentioning

confidence: 99%

“…The liver, adipose tissues, skeletal muscles, and vascular tissues are insulin-sensitive tissues responsible for blood glucose homeostasis (1,3). Inflammation adversely affects insulin sensitivity and worsens diabetic retinopathies, neuropathies, and vasculopathies (4)(5)(6).…”

mentioning

confidence: 99%

Niche-Dependent Regulations of Metabolic Balance in High-Fat Diet–Induced Diabetic Mice by Mesenchymal Stromal Cells

Chang

et al. 2014

Diabetes

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Mesenchymal stromal cells (MSCs) have great potential to maintain glucose homeostasis and metabolic balance. Here, we demonstrate that in mice continuously fed with high-fat diet (HFD) that developed non-insulindependent diabetes, two episodes of systemic MSC transplantations effectively improve glucose tolerance and blood glucose homeostasis and reduce body weight through targeting pancreas and insulin-sensitive tissues and organs via site-specific mechanisms. MSCs support pancreatic islet growth by direct differentiation into insulin-producing cells and by mitigating the cytotoxicity of interleukin 1 (IL-1) and tumor necrosis factor-a (TNF-a) in the pancreas. Localization of MSCs in the liver and skeletal muscles in diabetic animals is also enhanced and therefore improves glucose tolerance, although long-term engraftment is not observed. MSCs prevent HFD-induced fatty liver development and restore glycogen storage in hepatocytes. Increased expression of IL-1 receptor antagonist and Glut4 in skeletal muscles after MSC transplantation results in better blood glucose homeostasis. Intriguingly, systemic MSC transplantation does not alter adipocyte number, but it decreases HFD-induced cell infiltration in adipose tissues and reduces serum levels of adipokines, including leptin and TNF-a. Taken together, systemic MSC transplantation ameliorates HFD-induced obesity and restores metabolic balance through multisystemic regulations that are niche dependent. Such findings have supported systemic transplantation of MSCs to correct metabolic imbalance.Impairment of glucose tolerance and insulin resistance initiates type 2 diabetes; however, exhaustion of the insulin supply due to b-cell apoptosis is the ultimate pathomechanism of both type 1 and 2 diabetes (1,2). The liver, adipose tissues, skeletal muscles, and vascular tissues are insulin-sensitive tissues responsible for blood glucose homeostasis (1,3). Inflammation adversely affects insulin sensitivity and worsens diabetic retinopathies, neuropathies, and vasculopathies (4-6). Proinflammatory cytokines produced by macrophages, such as tumor necrosis factor-a (TNF-a) and interleukin 1 (IL-1), create a vicious cycle of reduced insulin sensitivity (3,(7)(8)(9).To the present, more than 300 clinical trials of mesenchymal stem/stromal cell (MSC) transplantations have been conducted worldwide with a wide clinical application targeting more than 50 indications (www.clinicaltrials.gov). Systemic transplantation is the most favorable route for MSC delivery from a safety and systemic regulation point of view, and 56% of MSC clinical trials are allogenic transplantation (10). It is well accepted that the majority of MSCs are initially distributed in vital organs (11-16) and are also frequently found in tissues of mesenchymal origin (11,12) when systemically administered. Nevertheless, the long-term engraftment of MSCs is minimal, and the engraftment rate is not correlated with therapeutic response in human studies (17). The acutely diseased and damaged tissues show increased loca...

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“…In addition to its role in atherosclerosis, LOX-1 also acts in the inflammatory process. Indeed, recent studies have shown that LOX-1 is involved in the activation of inflammatory processes and inflammation-related disorders [1][2][3][4][5]. Like most surface receptors, LOX-1 can be released in soluble form by proteolytic cleavage and this soluble form (sLOX-1) could be a serum marker in the monitoring of oxidative and/or inflammatory diseases such as sickle-cell disease.…”

Section: Introductionmentioning

confidence: 99%

Elevated Soluble Lectin-like oxidized LDL Receptor 1 (sLOX1) levels in sickle cell patients

2017

ajbpr

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Sickle-cell disease is characterized by chronic oxidative stress status with the resulting intense lipid peroxidation, and among the generated metabolites is the oxidized LDL. The latter thus modified are no longer recognized by the native receptors of LDL but by other types of receptors called "scavenger receptors", among which are LOX-1 (lectin-like oxidized LDL receptor). The capture of oxidized LDLs by vascular cells via scavenger receptors is a crucial step in the initiation and progression of atherosclerosis. Like most surface receptors, LOX-1 can be released in soluble form by proteolytic cleavage and this soluble form (sLOX-1) could be a serum marker in the monitoring of oxidative and/or inflammatory diseases such as Sickle cell disease. The objective of this work is to evaluate serum levels of sLOX-1 in sickle-cell patients and compare them to a control population. Our study involved 80 subjects, including 48 sickle-cell anemia and 32 controls. sLOX-1 was quantified using an Elisa method according to the manufacturer's instructions (Cloud-Clone Corp, Houston, USA) and other biochemical parameters on the Cobas 6000 (Roche, Mannheim, Germany). Our results showed serum levels of sLOX-1 significantly higher in sickle-cell patients population compared to controls (p <0.05). Moreover, sickle-cell patients had a higher risk of having increased sLOX1 (OR = 1.23).The high levels of sLOX-1 found in our study confirm our hypothesis and may reflect an increase in LOX-1 receptor expression during sickle-cell anemia.

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LOX-1, Oxidative Stress and Inflammation: A Novel Mechanism for Diabetic Cardiovascular Complications

Cited by 61 publications

References 92 publications

Serum sLOX-1 Levels Are Correlated with the Presence and Severity of Obstructive Sleep Apnea

Serum sLOX-1 Levels Are Correlated with the Presence and Severity of Obstructive Sleep Apnea

Niche-Dependent Regulations of Metabolic Balance in High-Fat Diet–Induced Diabetic Mice by Mesenchymal Stromal Cells

Elevated Soluble Lectin-like oxidized LDL Receptor 1 (sLOX1) levels in sickle cell patients

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