scholarly journals Lectin-like, oxidized low-density lipoprotein receptor-1-deficient mice show resistance to age-related knee osteoarthritis

2017 ◽  
Author(s):  
Kazuhiko Hashimoto ◽  
Yutaka Oda ◽  
Fumihisa Nakamura ◽  
Ryosuke Kakinoki ◽  
Masao Akagi
Keyword(s):  
Articular Chondrocytes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Expression Levels ◽  
Knee Oa ◽  
Age Related ◽  
Significant Difference ◽  
The Mean

The lectin-like, oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1)/ox-LDL system contributes to atherosclerosis and may be involved in cartilage degeneration. The purpose of this study was to determine whether the LOX-1/ox-LDL system contributes to age-related osteoarthritis (OA) in vivo, using LOX-1 knockout (LOX-1 KO) mice. Knee cartilage from 6, 12, and 18-month old (n = 10/group) C57Bl/6 wild-type (WT) and LOX-1 KO mice was evaluated by determining the Osteoarthritis Research Society International (OARSI) score of Safranin-O stained samples. The prevalence of knee OA in both mouse strains was also investigated. Expression levels of LOX-1, ox-LDL, runt-related transcription factor-2 (Runx2), type-X collagen (COL X), and matrix metalloproteinase-13 (MMP-13) in the articular chondrocytes were analyzed immunohistologically. No significant difference was observed in the mean scores of WT (2.00±0.61) and LOX-1 KO mice (2.00±0.49) at 6 months of age (P=1.00, n=10). At 12 and 18 months of age, the mean scores of LOX-1 KO mice (3.75±0.93 and 5.50±0.78) were significantly lower than those of WT mice (5.25±1.14 and 9.00±1.01; P<0.001 in both cases; n=10). The prevalence of OA in LOX-1 KO mice was lower than that in WT mice at 12 and 18 months of age (40 vs 70%, 70 vs 90%, respectively; n=10). The expression levels of Runx2, COL X, and MMP-13 in articular chondrocytes significantly decreased in LOX-1 KO, mice compared with those in WT mice. The study indicated that the LOX-1/ox-LDL system in chondrocytes plays a role in the pathogenesis of age-related knee OA, which is potentially a target for preventing OA progression.

Abstract 302: Presence of Oxidized Low-Density Lipoprotein in the Left Ventricular Blood of Subjects with Cardiovascular Diseases

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Chandrakala Aluganti Narasimhulu ◽  
Dmitry Litvinov ◽  
Danielle Jones ◽  
Chittoor Sai-Sudhakar ◽  
Michael Fristenberg ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Left Ventricular ◽  
Paraoxonase 1 ◽  
Left Ventricular Ejection ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Peripheral Tissues ◽  
Significant Difference

Hypothesis: Oxidized low density lipoprotein (Ox-LDL) has properties that profoundly affect cardiovascular function. We hypothesized that Ox-LDL is likely to be formed in the left ventricular blood (LVB) when the heart is subjected to ischemic conditions and the ejection fraction (EF) is low. We speculated whether “stagnation” of LDL in the LV could result in increased formation of Ox-LDL. Objective: We studied whether there is an increased level of Ox-LDL in the LVB as opposed to peripheral blood (PB), and whether its presence correlated with the EF. Also we examined whether a higher level of Ox-LDL negatively correlated with the activity of paraoxonase 1 (PON 1). Methods: Following the Institutional Review Board (IRB) approval, 62 HF patients were enrolled in the study. All patients underwent pre-operative transthoracic echocardiographic assessment of ventricular function. Left ventricular ejection fractions were determined using the Simpsons bi-plane technique. 2ml of LVB and 5ml of PB samples were taken before coronary artery bypass surgery, or a surgery with replacement of mitral, aortic or tricuspid valve. Blood level of Ox-LDL was determined by ELISA (Mercodia), and PON 1 activity was determined by the rate of conversion of its substrate p-nitrophenyl acetate into p-nitrophenol. Results: The result showed significant increase in Ox-LDL in LVB as compared to PB (p=0.032) in HF subjects even when EF was near normal. There was no significant increase in subjects with lower EF. In contrast, Ox-LDL levels increased in the PB of subjects with lower EF and reached those of LVB. We also noticed that there was a statistically significant negative correlation between EF and Ox-LDL levels in both LVB and PB (p < 0.05). The activity of PON1, an antioxidant enzyme that protects LDL from oxidation showed decreased levels both in LV blood as well as in PB with decreased EF. It was observed that there was a statistically significant difference in PON1 levels between LV and PB of subjects having EF>60% (p = 0.03). Conclusions: In conclusion the results suggest that there might be oxidative stress associated with LVB even when the EF is not compromised. In contrast, the increase in PB Ox-LDL with poor EF might suggest that the low blood flow to peripheral tissues and end organs also might contribute to increased oxidative stress. The results also might suggest that persistent oxidative stress could have affected the clearance mechanisms of Ox-LDL.

scholarly journals The effect of genistein on lipid levels and LDLR, LXRα and ABCG1 expression in postmenopausal women with hyperlipidemia

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Tao Zhang ◽  
Xiao-Xing Chi
Keyword(s):  
Mrna Expression ◽  
Postmenopausal Women ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Apolipoprotein A1 ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Expression Levels ◽  
Significant Difference ◽  
Mrna Expression Levels

Abstract Background This study investigates the effect of genistein (Gen) on the lipid profiles and expression of low-density lipoprotein receptor (LDLR), liver X receptor α (LXRα) and ATP-binding cassette transporter G1 (ABCG1) in the plasma macrophages of postmenopausal women with hyperlipidemia in China. Methods This study considered 187 cases, where 160 postmenopausal women had hyperlipidemia. The subjects were divided into placebo group (PG) and experimental group (EG). EG received 60 mg/day of Gen, PG received placebo for 6 months. Body weight, height, waist circumference, body mass index and glucose levels were determined according to standard operating procedures. The triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein-A1 (Apo-A1) and apolipoprotein-B (Apo-B) levels were detected in the plasma macrophages using ELISA. The protein and mRNA expression levels of LDLR, LXRα and ABCG1 were detected by western blot and real-time PCR techniques, respectively. Results Compared to the baseline, Gen effectively lowered TG, TC and LDL-C levels, whereas HDL-C levels as well as the protein and mRNA expression levels of LDLR, LXRα and ABCG1 (p < 0.05) were increased. There was a significant difference in the expression of LDLR protein between the two groups (p < 0.05). The mRNA expression levels of LDLR, LXRα and ABCG1 were significantly increased in the EG compared to the PG. Conclusion Gen effectively modulated the plasma lipid indices. The cholesterol-lowering effects of Gen may be attributed to its regulation on some of the key genes involved in cholesterol homeostasis.

scholarly journals Oxidized Low-density Lipoprotein and the Incidence of Age-related Macular Degeneration

Ophthalmology ◽  
2019 ◽  
Vol 126 (5) ◽  
pp. 752-758 ◽  
Author(s):  
Ronald Klein ◽  
Kristine E. Lee ◽  
Michael Y. Tsai ◽  
Karen J. Cruickshanks ◽  
Ronald E. Gangnon ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Age Related Macular Degeneration ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Age Related
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