The Association between the Lipids Levels in Blood and Risk of Age-Related Macular Degeneration

Wang, Yafeng; Wang, Mingxu; Zhang, Xiaoqing; Zhang, Qianyu; Nie, Jing; Zhang, Ming; Liu, Xiaohong; Ma, Le

doi:10.3390/nu8100663

Cited by 65 publications

(45 citation statements)

References 47 publications

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“…Meanwhile, OX-LDL stimulation disrupts RPE barrier and induces VEGF/PDGF secretion in ARPE-19 cells, which further indicates the pathogenic mechanism of lipid oxidation to exudative AMD. Clinical trials have revealed the association between serum lipid levels and AMD [ 32 ]. However, little is known about oxidative damage of OX-LDL to CNV pathology in vivo.…”

Section: Discussionmentioning

confidence: 99%

Salvianolic Acid A Inhibits OX‐LDL Effects on Exacerbating Choroidal Neovascularization via Downregulating CYLD

Mao

Shu

Liu

et al. 2017

Oxidative Medicine and Cellular Longevity

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Backgrounds Age-related macular degeneration is closely related to lipid oxidation, while relationship between OX-LDL and choroidal neovascularization is unclear. Recently, cylindromatosis is proved to regulate angiogenesis. However, its role in CNV progression remained unclear. Salvianolic acid A is widely used in vascular diseases. We investigated the relationship between OX-LDL and CNV and explore antineovascularization mechanism of Sal A. Methods C57BL6/J mice were randomized into four groups and injected with PBS or OX-LDL, together with Sal A for one week. CNV was induced by laser; CNV severity was analyzed by fundus fluorescein angiography, H&E staining, and choroid flat mount after 1 week. In in vitro experiments, ARPE-19 and HUVECs were cultured with OX-LDL (with or without Sal A) for 48 hours. Angiogenic proteins, cell junction integrity, and tube formation were measured. CYLD siRNA and specific inhibitors were used to explore mechanisms of CYLD in promoting OX-LDL-induced CNV progression. Results OX-LDL promoted laser-induced CNV volume by increasing VEGF, PDGF, and CYLD levels. Sal A antagonized OX-LDL effects and restrained CNV progression by decreasing VEGF/PDGF/CYLD, increasing antiangiostatin levels, and promoting P62-CYLD-TRAF6 interaction. Conclusions We demonstrated oxidation damage exacerbates CNV progression, and Sal A could be a clinical therapeutic reagent to exudative AMD.

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Section: Discussionmentioning

confidence: 99%

Salvianolic Acid A Inhibits OX‐LDL Effects on Exacerbating Choroidal Neovascularization via Downregulating CYLD

Mao

Shu

Liu

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…Statins (e.g., atorvastatin and lovastatin), common cholesterol-lowering medications, are inhibitors for 3-hydroxy-3-methylglutaryl coenzyme A reductase, and have recently been reported to be useful for decreasing the risk of wet-type AMD [44] . Statin-induced decrease in serum low-density lipoprotein (LDL) cholesterol might reduce LDL cholesterol deposits in the drusen, which plays a key role in the pathogenesis of AMD [45] . In addition to lipid-lowering effects, statins also exert anti-inflammatory effects through inhibition of the inflammatory pathway [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Statins decrease vascular epithelial growth factor expression via down-regulation of receptor for advanced glycation end-products

Tsujinaka

Itaya‐Hironaka

Yamauchi

et al. 2017

Heliyon

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AimsStatins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, possess pleiotropic effects that have been extended to modulation of various cellular behaviors. This study aimed to examine whether statins modulate vascular endothelial growth factor A (VEGF-A) expression in human retinal pigment epithelium (RPE) cells.Main methodsHuman RPE cells (h1RPE7), damaged by hydroquinone (HQ) + advanced glycation endproducts (AGE) in an in vitro AMD model, were treated with atorvastatin or lovastatin for 24 h. The expression of VEGF-A and receptor for AGE (RAGE) was evaluated by real-time RT-PCR. VEGF-A secretion was measured by ELISA. To investigate the impact of RAGE on VEGF-A expression, small interfering RNA (siRNA) for RAGE (siRAGE) was introduced into h1RPE7 cells and VEGF-A expression was measured by real-time RT-PCR. Deletions of VEGF-A and RAGE promoters were performed and transcriptional activities were measured after the addition of statins to HQ + AGE-damaged RPE cells.Key findingsThe mRNA levels of VEGF-A and RAGE and the levels of VEGF-A in the culture medium were increased by HQ + AGE. Both atorvastatin and lovastatin attenuated HQ + AGE-induced VEGF-A and RAGE expression. These statins also decreased VEGF-A levels in the culture medium. RNA interference of RAGE attenuated the up-regulation of VEGF-A in the HQ + AGE treated cells. The deletion analysis demonstrated that these statins attenuated RAGE promoter activation in HQ + AGE-damaged RPE cells.SignificanceStatins attenuated HQ + AGE-induced VEGF expression by decreasing RAGE expression. As VEGF is an important factor in developing wet AMD, statins could decrease the risk of wet-type AMD and be used as preventive medicines.

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“…These findings suggest that HDL is involved in pro-inflammatory as well as complement inhibitory tasks. Higher HDL levels may cause imbalance of the physiological homeostasis 8,63 . Taken together, this plethora of biological leads supports the contention that HDL may play a role in the initiation of AMD.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration

Colijn¹,

Hollander²,

Demirkan³

et al. 2019

Ophthalmology

111

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Genetic and epidemiologic studies have shown that lipid genes and High Density Lipoproteins (HDL) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relation to AMD in a large European dataset, and investigated whether this relationship is driven by certain sub fractions. Design: (Pooled) analysis of cross-sectional data. Participants: 30,953 individuals aged 50+ participating in the E3 consortium; and 1530 individuals from the Rotterdam Study with lipid sub fraction data. Methods: In E3, AMD features were graded per eye on fundus photographs using the Rotterdam Classification. Routine blood lipid measurements were available from each participant. Data on genetics, medication and confounders such as body mass index, were obtained from a common database. In a subgroup of the Rotterdam Study, lipid sub fractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random-effect were used to estimate the associations. Main Outcome Measures: early, late or any AMD, phenotypic features of early AMD, lipid measurements. Results: HDL was associated with an increased risk of AMD, corrected for potential confounders (Odds Ratio (OR) 1.21 per 1mmol/L increase (95% confidence interval[CI] 1.14-1.29); while triglycerides were associated with a decreased risk (OR 0.94 per 1mmol/L increase [95%CI 0.91-0.97]). Both were associated with drusen size, higher HDL raises the odds of larger drusen while higher triglycerides decreases the odds. LDL-cholesterol only reached statistical significance in the association with early AMD (p=0.045). Regarding lipid sub fractions: the concentration of extra-large HDL particles showed the most prominent association with AMD (OR 1.24 [95%CI 1.10-1.40]). The CETP risk variant (rs17231506) for AMD was in line with increased-HDL levels (p=7.7x10-7); but LIPC risk variants (rs2043085, rs2070895) were associated in an opposite way (p=1.0x10-6 and 1.6x10-4). Conclusions: Our study suggests that HDL-cholesterol is associated with increased risk of AMD and triglycerides negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL sub fractions seem to be drivers in the relation with AMD, variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains a question to be answered.

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The Association between the Lipids Levels in Blood and Risk of Age-Related Macular Degeneration

Cited by 65 publications

References 47 publications

Salvianolic Acid A Inhibits OX‐LDL Effects on Exacerbating Choroidal Neovascularization via Downregulating CYLD

Salvianolic Acid A Inhibits OX‐LDL Effects on Exacerbating Choroidal Neovascularization via Downregulating CYLD

Statins decrease vascular epithelial growth factor expression via down-regulation of receptor for advanced glycation end-products

Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration

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