Elevation of a Novel Angiogenic Factor, Leucine-Rich-α2-Glycoprotein (LRG1), Is Associated With Arterial Stiffness, Endothelial Dysfunction, and Peripheral Arterial Disease in Patients With Type 2 Diabetes

Pek, Sharon Li Ting; Tavintharan, Subramaniam; Wang, Xiaomeng; Lim, Su Chi; Woon, Kaing; Yeoh, Lee Ying; Ng, Xiao Wei; Liu, Jing; Sum, Chee Fang

doi:10.1210/jc.2014-3855

Cited by 88 publications

(74 citation statements)

References 31 publications

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“…More recently, we reported, in a cohort of patients with type 2 diabetes, higher circulating LRG1 in those with peripheral arterial disease compared to those without . We observed LRG1 to be positively associated with measures of obesity [body mass index (BMI) and waist circumference].…”

Section: Introductionmentioning

confidence: 75%

“…Plasma LRG1 was measured by commercially available ELISA kits (Immuno‐Biological Laboratories, Gunma, Japan) as described previously . Our intraplate coefficient of variation (CV) was 5.65%, and interplate CV was 9.37%.…”

Section: Methodsmentioning

confidence: 99%

“…Our inclusion of 231 patients, with presurgery and follow‐up weight measurement, is sufficiently powered to reject the null hypothesis. The calculation of sample size was based on the LRG1 values (SD) in nondiabetic, normal weight individuals as well as our previous data of β between LRG1 and BMI . Results for continuous variables with normal distribution were presented in mean ± SD; medians and interquartile ranges were presented for continuous but non‐normally distributed variables.…”

Section: Methodsmentioning

confidence: 99%

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Association of circulating proinflammatory marker, leucine‐rich‐α2‐glycoprotein (LRG1), following metabolic/bariatric surgery

Pek

Cheng

Lin

et al. 2018

Diabetes Metabolism Res

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Section: Introductionmentioning

confidence: 75%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Association of circulating proinflammatory marker, leucine‐rich‐α2‐glycoprotein (LRG1), following metabolic/bariatric surgery

Pek

Cheng

Lin

et al. 2018

Diabetes Metabolism Res

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“…Chronic kidney disease (CKD) was defined by the presence of eGFR <60 ml/min/1.73m 2 or kidney damage as indicated by ACR≥30mg/g [23]. Assessment for neuropathy was performed by a neurothesiometer (Horwell Scientific, Wilford, Nottingham, UK) for vibration and with a 10-g monofilament for light touch as described previously [24]. Neuropathy was present if an abnormal finding in monofilament (inability to detect at least 8 of 10 points on either foot) or neurothesiometer testing of ≥ 25 V was detected [24].…”

Section: Methodsmentioning

confidence: 99%

Direct medical cost associated with diabetic retinopathy severity in type 2 diabetes in Singapore

et al. 2017

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Diabetic retinopathy (DR) is a leading cause of vision-loss globally among type 2 diabetes (T2DM) patients. Information on the economic burden of DR in Singapore is limited. We aim to identify the total annual direct medical costs of DR at different stages, and to examine factors influencing the costs. Four hundreds and seventy T2DM patients who attended the Diabetes Centre in a secondary hospital in Singapore in 2011–2014 were included. Digital color fundus photographs were assessed for DR in a masked fashion. Retinopathy severity was further categorized into non-proliferative DR (NPDR), including mild, moderate and severe NPDR, and proliferative DR (PDR). Medical costs were assessed using hospital administrative data. DR was diagnosed in 172 (39.5%) patients, including 51 mild, 62 moderate and 18 severe NPDR, and 41 PDR. The median cost in DR [2012.0 (1111.2–4192.3)] was significantly higher than that in non-DR patients [1158.1 (724.1–1838.9)] (p<0.001). The corresponding costs for mild, moderate, severe NPDR and PDR were [1167.1 (895.4–2012.0)], [2212.0 (1215.5–3825.5)], [2717.5 (1444.0–6310.7)], and [3594.8.1 (1978.4–8427.7)], respectively. After adjustment, the corresponding cost ratios for mild, moderate, severe NPDR, and PDR relative to non-DR were 1.1 (p = 0.827), 1.8 (p = 0.003), 2.0 (p = 0.031) and 2.3 (p<0.001), respectively. The other factors affecting the total cost include smoking (ratio = 1.7, p = 0.019), neuropathy (ratio = 1.9, p = 0.001) and chronic kidney disease (CKD) (ratio = 1.4, p = 0.019). The presence and severity of DR was associated with increased direct medical costs in T2DM. Our results suggest that preventing progression of DR may reduce the economic burden of DR.

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“…Additionally, the function of LRG1 in tumors was investigated, and indicated that LRG1 was associated with multiple types of tumor, including ovarian cancer, glioblastoma and squamous cell lung cancer (15–18). Furthermore, certain previous studies reported that LRG1 is involved in various diseases, including inflammatory diseases, heart failure, arterial stiffness, endothelial dysfunction and peripheral arterial disease (19–23). Previously, LRG1 expression in the brain during aging and neurodegenerative diseases, including idiopathic normal pressure hydrocephalus, Parkinson's disease with dementia, dementia with Lewy bodies, progressive nuclear palsy and Alzheimer's disease was investigated (24,25).…”

Section: Introductionmentioning

confidence: 99%

LRG1 promotes angiogenesis through upregulating the TGF-β1 pathway in ischemic rat brain

Meng

Song

Zhu

et al. 2016

Molecular Medicine Reports

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Stroke is a life-threatening disease that results in significant disability in the human population. Despite the advances in current stroke therapies, a host of patients do not benefit from the conventional treatments. Thus, more effective therapies are required. It has been previously reported that leucine-rich-α2-glycoprotein 1 (LRG1) is crucial during the formation of new blood vessels in retinal diseases. However, the function of LRG1 in the brain during the neovessel growth process following ischemic stroke has not been fully elucidated and the mechanism underlying its effect on angiogenesis remains unclear. The purpose of the current study was to demonstrate whether LRG1 may promote angiogenesis through the transforming growth factor (TGF)-β1 signaling pathway in ischemic rat brain following middle cerebral artery occlusion (MCAO). In the present study, the spatial and temporal expression of LRG1, TGF-β1, vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) were detected in ischemic rat brain following MCAO using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunohistochemistry. CD34 immunohistochemistry staining was used as an indicator of microvessel density (MVD). The RT-qPCR and western blotting results revealed that the levels of LRG1 and TGF-β1 mRNA and protein expression were significantly increased as early as 6 and 12 h after MCAO (P<0.05), respectively, peaked at 3 days and persisted at significantly higher level until 14 days, in comparison with the control group. Additionally, VEGF and Ang-2 were also increased following MCAO. Furthermore, the immunohistochemistry results suggested that the MVD was increased following MCAO. In addition, the results also revealed that the percentage of LRG1-positive cells was positively correlated with the percentage of TGF-β1-positive cells, and the percentage of LRG1-positive and TGF-β1-positive cells had a positively correlation with the MVD. Taken together, the present study indicated that LRG1 may promote angiogenesis through upregulating the TGF-β1 signaling pathway in ischemic rat brain following MCAO. This may provide a potential therapeutic target for the treatment of ischemic stroke.

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Elevation of a Novel Angiogenic Factor, Leucine-Rich-α2-Glycoprotein (LRG1), Is Associated With Arterial Stiffness, Endothelial Dysfunction, and Peripheral Arterial Disease in Patients With Type 2 Diabetes

Cited by 88 publications

References 31 publications

Association of circulating proinflammatory marker, leucine‐rich‐α2‐glycoprotein (LRG1), following metabolic/bariatric surgery

Association of circulating proinflammatory marker, leucine‐rich‐α2‐glycoprotein (LRG1), following metabolic/bariatric surgery

Direct medical cost associated with diabetic retinopathy severity in type 2 diabetes in Singapore

LRG1 promotes angiogenesis through upregulating the TGF-β1 pathway in ischemic rat brain

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