Sex differences in corneal neovascularization in response to superficial corneal cautery in the rat

Irani, Yazad; Pulford, Emily; Mortimer, Lauren; Irani, Swati; Butler, Lisa M.; Klebe, Sonja; Williams, Keryn A.

doi:10.1371/journal.pone.0221566

Cited by 7 publications

(5 citation statements)

References 64 publications

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“…46 Also, recent studies provided evidence that male rats and humans are more prone to corneal neovascularization than females and that males had a higher level of pro-atherogenic molecules, including VEGF (vascular endothelial growth factor)-A, VEGF receptor (VEGFR)1, VEGFR2, and IGFBP2, than females. 47,48 In contrast, Rudnicki et al 49 showed that female adipose mice and human EC have higher proliferation and angiogenesis and less inflammation than male adipose EC females. In addition, using male and female human umbilical vein EC, Cattaneo et al 50 observed that male cells had higher apoptotic rates in response to serum starvation conditions and identified protein PTX3 (pentraxin-related protein 3) as a potential mediator of this apoptotic response and discovered that female EC expressed higher levels of eNOS (endothelial nitric oxide synthase).…”

Section: Discussionmentioning

confidence: 99%

Unraveling the Role of Sex in Endothelial Cell Dysfunction: Evidence From Lineage Tracing Mice and Cultured Cells

Shin,

Hong,

Edwards-Glenn

et al. 2024

ATVB

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BACKGROUND: Biological sex differences play a vital role in cardiovascular diseases, including atherosclerosis. The endothelium is a critical contributor to cardiovascular pathologies since endothelial cells (ECs) regulate vascular tone, redox balance, and inflammatory reactions. Although EC activation and dysfunction play an essential role in the early and late stages of atherosclerosis development, little is known about sex-dependent differences in EC. METHODS: We used human and mouse aortic EC as well as EC-lineage tracing ( Cdh5 -CreERT2 Rosa-YFP [yellow fluorescence protein]) atherosclerotic Apoe –/– mice to investigate the biological sexual dimorphism of the EC functions in vitro and in vivo. Bioinformatics analyses were performed on male and female mouse aortic EC and human lung and aortic EC. RESULTS: In vitro, female human and mouse aortic ECs showed more apoptosis and higher cellular reactive oxygen species levels than male EC. In addition, female mouse aortic EC had lower mitochondrial membrane potential (ΔΨm), lower TFAM (mitochondrial transcription factor A) levels, and decreased angiogenic potential (tube formation, cell viability, and proliferation) compared with male mouse aortic EC. In vivo, female mice had significantly higher lipid accumulation within the aortas, impaired glucose tolerance, and lower endothelial-mediated vasorelaxation than males. Using the EC-lineage tracing approach, we found that female lesions had significantly lower rates of intraplaque neovascularization and endothelial-to-mesenchymal transition within advanced atherosclerotic lesions but higher incidents of missing EC lumen coverage and higher levels of oxidative products and apoptosis. RNA-seq analyses revealed that both mouse and human female EC had higher expression of genes associated with inflammation and apoptosis and lower expression of genes related to angiogenesis and oxidative phosphorylation than male EC. CONCLUSIONS: Our study delineates critical sex-specific differences in EC relevant to proinflammatory, pro-oxidant, and angiogenic characteristics, which are entirely consistent with a vulnerable phenotype in females. Our results provide a biological basis for sex-specific proatherosclerotic mechanisms.

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Section: Discussionmentioning

confidence: 99%

Unraveling the Role of Sex in Endothelial Cell Dysfunction: Evidence From Lineage Tracing Mice and Cultured Cells

Shin,

Hong,

Edwards-Glenn

et al. 2024

ATVB

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“…The effects were more pronounced in males than females, and NHMI administration increased the frequency of hyperplastic lesions with augmentation by chrysotile (although this was not statistically significant), but a 'promoting' effect of chrysotile was observed for the induction of lung tumors (all but two out of 11 primary tumors were in rats treated with both NHMI and chrysotile), although this finding was not confirmable statistically because of the small number of tumors observed. A sex difference in inflammatory responses involving higher expression of Cox-2, VEGF-A, and VEGF-R2 in males compared with females has recently been observed in other models [95], and consequently, research bodies now recommend use of sex-matched cohorts [96].…”

Section: The Synergy Between Asbestos Fibers and Tobacco Smoke For Lung Cancer Causation-animal Studiesmentioning

confidence: 99%

Asbestos, Smoking and Lung Cancer: An Update

Klebe

Leigh

Henderson

et al. 2019

IJERPH

Self Cite

104

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This review updates the scientific literature concerning asbestos and lung cancer, emphasizing cumulative exposure and synergism between asbestos exposure and tobacco smoke, and proposes an evidence-based and equitable approach to compensation for asbestos-related lung cancer cases. This update is based on several earlier reviews written by the second and third authors on asbestos and lung cancer since 1995. We reevaluated the peer-reviewed epidemiologic studies. In addition, selected in vivo and in vitro animal studies and molecular and cellular studies in humans were included. We conclude that the mechanism of lung cancer causation induced by the interdependent coaction of asbestos fibers and tobacco smoke at a biological level is a multistage stochastic process with both agents acting conjointly at all times. The new knowledge gained through this review provides the evidence for synergism between asbestos exposure and tobacco smoke in lung cancer causation at a biological level. The evaluated statistical data conform best to a multiplicative model for the interaction effects of asbestos and smoking on the lung cancer risk, with no requirement for asbestosis. Any asbestos exposure, even in a heavy smoker, contributes to causation. Based on this information, we propose criteria for the attribution of lung cancer to asbestos in smokers and non-smokers.

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“…COX-2 is an inducible enzyme, which not only participates in various inflammatory reactions but also plays a role in the process of angiogenesis. Under various stimuli, its expression is slightly up-regulated (23)(24)(25). VEGF is closely related to the formation of new blood vessels.…”

Section: Corneal Cox-2 and Vegf Gene Mrna Level Detection Resultsmentioning

confidence: 99%

The Effect of Bromfenac Sodium Nanopolymer Used in Anterior Segment of the Eye on Corneal Neovascularization

Li¹,

Liu²,

Chen³

et al. 2022

Cell Mol Biol (Noisy-le-grand)

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This study was to explore the inhibitory effect of bromfenac sodium (BF) / chitosan (CS) nanoparticles (NPs) on corneal neovascularization (CNV). 45 New Zealand white rabbits provided by The First Affiliated Hospital of Jinan University were randomly divided into a control group (group A, n = 15), 0.1% BF aqueous solution treatment group (group B, n = 15), and 0.1% BF/CS-NPs suspension treatment group (group C, n = 15). A rabbit corneal alkali burn model was established. The average particle size of BF/CS-NPs with different BF concentrations was mainly 341.6 ± 12.9 nm -548.7 ± 15.4 nm; and the Zeta potential distribution was 24.3 ± 2.5 mV -35.7 ± 4.3 mV. When the initial concentration of BF was 1.5 mg/mL, the maximum drug loading was 57.35 ± 5.26%. The area of CNV in group C was significantly lower than that in groups B and A, and the differences were statistically significant (P < 0.05). At 6, 12, 18, and 24 days after surgery, the mRNA expression levels in cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) gene were compared after standardized by β-actin; group A had the highest expression level, followed by group B, and group C had the lowest expression level, showing statistically significant differences (P < 0.05). The BF/CS-NPs granules prepared in this study had stable physical and chemical properties and had a good sustainedrelease effect, and the release duration can be as long as 48 hours. BF/CS-NPs can inhibit the formation of CNV at different time points after alkali burn, and reduce the expression of VEGF and COX-2 in corneal tissue after alkali burn.

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Sex differences in corneal neovascularization in response to superficial corneal cautery in the rat

Cited by 7 publications

References 64 publications

Unraveling the Role of Sex in Endothelial Cell Dysfunction: Evidence From Lineage Tracing Mice and Cultured Cells

Unraveling the Role of Sex in Endothelial Cell Dysfunction: Evidence From Lineage Tracing Mice and Cultured Cells

Asbestos, Smoking and Lung Cancer: An Update

The Effect of Bromfenac Sodium Nanopolymer Used in Anterior Segment of the Eye on Corneal Neovascularization

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