High Glucose Activates ChREBP-Mediated HIF-1α and VEGF Expression in Human RPE Cells Under Normoxia

Chang, Min-Lee; Chiu, Chung‐Jung; Shang, Fu; Taylor, Allen

doi:10.1007/978-1-4614-3209-8_77

Cited by 30 publications

(19 citation statements)

References 29 publications

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“…An understanding of the mechanisms can elucidate the conditions under which dietary intervention will be most effective, help to identify target populations who may receive optimal benefits, help to define interactions or synergistic effects with other concurrent interventions, and suggest potential biomarkers for the prediction of AMD. 36, 37 In addition, our results also suggest that nutritional disparity plays a role in the distribution of AMD. Studies to understand the causes behind this nutritional disparity may offer important information for policy interventions to reduce the occurrence of AMD and related health care burden.…”

Section: Discussionsupporting

confidence: 63%

The Relationship of Major American Dietary Patterns to Age-Related Macular Degeneration

Chiu

Chang

Zhang

et al. 2014

American Journal of Ophthalmology

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PURPOSE We hypothesized that major American dietary patterns are associated with age-related macular degeneration (AMD) risk. DESIGN Cross-sectional study METHODS 8,103 eyes from 4,088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into control (n=2,739), early AMD (n=4,599), and advanced AMD (n=765) by AREDS AMD Classification System. Food consumption data were collected by a 90-item food frequency questionnaire. RESULTS Two major dietary patterns were identified by factor (principle component) analysis based on 37 food groups and named Oriental and Western patterns. The Oriental pattern was characterized by higher intake of vegetables, legumes, fruit, whole grains, tomatoes, and seafood. The Western pattern was characterized by higher intake of red meat, processed meat, high-fat dairy products, French fries, refined grains, and eggs. We ranked our participants according to how closely their diets line up with the two patterns by calculating the two factor scores for each participant. For early AMD, multivariate-adjusted odds ratio (OR) from generalized estimating equation logistic analysis comparing the highest to lowest quintile of the Oriental pattern score was ORE5O=0.74 (95% confidence interval (CI): 0.59–0.91; Ptrend=0.01), and the OR comparing the highest to lowest quintile of the Western pattern score was ORE5W=1.56 (1.18–2.06; Ptrend=0.01). For advanced AMD, the ORA5O was 0.38 (0.27–0.54; Ptrend<0.0001), and the ORA5W was 3.70 (2.31–5.92; Ptrend<0.0001). CONCLUSIONS Our data indicate that overall diet is significantly associated with the odds of AMD and that dietary management as an AMD prevention strategy warrants further study.

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Section: Discussionsupporting

confidence: 63%

The Relationship of Major American Dietary Patterns to Age-Related Macular Degeneration

Chiu

Chang

Zhang

et al. 2014

American Journal of Ophthalmology

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“…The increased VEGF levels measured in hyperglucidic media of cultured nCMs suggests that the expression pattern of VEGF could vary significantly between neonatal and adult cardiomyocytes exposed to hyperglucidic environment. On the other hand, it has been shown in vitro that high glucose induces VEGF expression in several cell types such as retinal pigmented [44], vascular smooth muscle [45], and mesangial [46] cells. In addition, VEGF concentration has been reported to be significantly increased in the developing hearts of the embryos from diabetic mice [47].…”

Section: Discussionmentioning

confidence: 99%

Parenchymal and Stromal Cells Contribute to Pro-Inflammatory Myocardial Environment at Early Stages of Diabetes: Protective Role of Resveratrol

et al. 2016

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Background: Little information is currently available concerning the relative contribution of cardiac parenchymal and stromal cells in the activation of the pro-inflammatory signal cascade, at the initial stages of diabetes. Similarly, the effects of early resveratrol (RSV) treatment on the negative impact of diabetes on the different myocardial cell compartments remain to be defined. Methods: In vitro challenge of neonatal cardiomyocytes and fibroblasts to high glucose and in vivo/ex vivo experiments on a rat model of Streptozotocin-induced diabetes were used to specifically address these issues. Results: In vitro data indicated that, besides cardiomyocytes, neonatal fibroblasts contribute to generating initial changes in the myocardial environment, in terms of pro-inflammatory cytokine expression. These findings were mostly confirmed at the myocardial tissue level in diabetic rats, after three weeks of hyperglycemia. Specifically, monocyte chemoattractant protein-1 and Fractalkine were up-regulated and initial abnormalities in cardiomyocyte contractility occurred. At later stages of diabetes, a selective enhancement of pro-inflammatory macrophage M1 phenotype and a parallel reduction of anti-inflammatory macrophage M2 phenotype were associated with a marked disorganization of cardiomyocyte ultrastructural properties. RSV treatment inhibited pro-inflammatory cytokine production, leading to a recovery of cardiomyocyte contractile efficiency and a reduced inflammatory cell recruitment. Conclusion: Early RSV administration could inhibit the pro-inflammatory diabetic milieu sustained by different cardiac cell types.

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“…HIF-1a is a known factor that can induce LRP1 expression in cardiomyocytes 42 and in other cell types. [43][44][45][46] These effects were lost following chronic diabetes, and could contribute to the development of cardiomyopathy in these animals. The disappearance of LRP1, with prolonged duration of diabetes, may be related to a further attenuation of myocytes pooled from four independent experiments.…”

Section: Discussionmentioning

confidence: 99%

High glucose facilitated endothelial heparanase transfer to the cardiomyocyte modifies its cell death signature

Wang

Jia

Lal

et al. 2016

Cardiovascular Research

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Aims The secretion of enzymatically active heparanase (HepA) has been implicated as an essential metabolic adaptation in the heart following diabetes. However, the regulation and function of the enzymatically inactive heparanase (HepL) remain poorly understood. We hypothesized that in response to high glucose (HG) and secretion of HepL from the endothelial cell (EC), HepL uptake and function can protect the cardiomyocyte by modifying its cell death signature. Methods and results HG promoted both HepL and HepA secretion from microvascular (rat heart micro vessel endothelial cells, RHMEC) and macrovascular (rat aortic endothelial cells, RAOEC) EC. However, only RAOEC were capable of HepL reuptake. This occurred through a low-density lipoprotein receptor-related protein 1 (LRP1) dependent mechanism, as LRP1 inhibition using small interfering RNA (siRNA), receptor-associated protein, or an LRP1 neutralizing antibody significantly reduced uptake. In cardiomyocytes, which have a negligible amount of heparanase gene expression, LRP1 also participated in the uptake of HepL. Exogenous addition of HepL to rat cardiomyocytes produced a dramatically altered expression of apoptosis-related genes, and protection against HG and H2O2 induced cell death. Cardiomyocytes from acutely diabetic rats demonstrated a robust increase in LRP1 expression and levels of heparanase, a pro-survival gene signature, and limited evidence of cell death, observations that were not apparent following chronic and progressive diabetes. Conclusion Our results highlight EC-to-cardiomyocyte transfer of heparanase to modulate the cardiomyocyte cell death signature. This mechanism was observed in the acutely diabetic heart, and its interruption following chronic diabetes may contribute towards the development of diabetic cardiomyopathy.

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High Glucose Activates ChREBP-Mediated HIF-1α and VEGF Expression in Human RPE Cells Under Normoxia

Abstract: These results suggest a high glucose-induced, ChREBP-mediated, and normoxic HIF-1α activation that may be partially responsible for neovascularization in both diabetic and age-related retinopathy.

Cited by 30 publications

References 29 publications

The Relationship of Major American Dietary Patterns to Age-Related Macular Degeneration

The Relationship of Major American Dietary Patterns to Age-Related Macular Degeneration

Parenchymal and Stromal Cells Contribute to Pro-Inflammatory Myocardial Environment at Early Stages of Diabetes: Protective Role of Resveratrol

High glucose facilitated endothelial heparanase transfer to the cardiomyocyte modifies its cell death signature

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