Fenofibrate regulates retinal endothelial cell survival through the AMPK signal transduction pathway

Kim, Jaetaek; Ahn, Jeongmin; Kim, Jeong-Hun; Yu, Young Suk; Kim, Ho‐Shik; Ha, Joohun; Shinn, Soon-Hyun; Oh, Yeon-Sahng

doi:10.1016/j.exer.2007.01.009

Cited by 105 publications

(79 citation statements)

References 43 publications

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“…These results suggest that fenofibrate prevents apoptotic cell death induced by serum deprivation through PPARa-independent, but AMPK-dependent pathway resulting in a novel therapeutic property that may control unwanted cell death found in diabetic retinopathy. 40,41 The trial data do not clarify which mechanism is important clinically. In particular the FIELD study suggested that it may be independent of lipid lowering as there was no difference in the lipid levels of those requiring laser or not, although this was in contrast to the ACCORD Eye data that did show a difference in triglyceride levels.…”

Section: Mechanism Of Function Of Fenofibratementioning

confidence: 99%

Medical management of diabetic retinopathy: fenofibrate and ACCORD Eye studies

Wright

Dodson

2011

Eye

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The approach of all ophthalmologists, diabetologists and general practitioners seeing patients with diabetic retinopathy should be that good control of blood glucose, blood pressure and plasma lipids are all essential components of modern medical management. The more recent data on the use of fenofibrate in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye studies is reviewed. In FIELD, fenofibrate (200 mg/day) reduced the requirements for laser therapy and prevented disease progression in patients with preexisting diabetic retinopathy. In ACCORD Eye, fenofibrate (160 mg daily) with simvastatin resulted in a 40% reduction in the odds of retinopathy progressing over 4 years, compared with simvastatin alone. This occurred with an increase in HDL-cholesterol and a decrease in the serum triglyceride level in the fenofibrate group, as compared with the placebo group, and was independent of glycaemic control. We believe fenofibrate is effective in preventing progression of established diabetic retinopathy in type 2 diabetes and should be considered for patients with pre-proliferative diabetic retinopathy and/or diabetic maculopathy, particularly in those with macular oedema requiring laser.

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Section: Mechanism Of Function Of Fenofibratementioning

confidence: 99%

Medical management of diabetic retinopathy: fenofibrate and ACCORD Eye studies

Wright

Dodson

2011

Eye

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show abstract

“…[55] The mechanism behind this novel property of fenoÞ brate may be the result of its antiapoptotic activity in retinal endothelial cells, independent of its lipid lowering activity. [56] …”

Section: Importance Of Serum Lipid Controlmentioning

confidence: 99%

Diabetic retinopathy: A comprehensive review

Shah¹

2008

Indian J Med Sci

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“…(48) In the present study, fenofibrate pretreatment increased activated AMPK (phospho AMPK Thr 172) levels compared to TNF-alpha only treatment, which corresponds with the increased activation of eNOS. In this regard, fenofibrate has previously been associated with increased phosphorylation of AMPK (Thr 172) in a variety of endothelial cell types; (9,37,49,50) however, none of these studies were conducted in the context of TNF-alpha induced injury. Tomizawa, et al (2011) showed that 100μM fenofibrate activates AMPK and Akt in human glomerular microvascular endothelial cells with resultant activation of eNOS (Ser 1177) within 1 hour of treatment.…”

Section: Discussionmentioning

confidence: 99%

“…These findings were observed at a concentration of 30μM at 10 minutes. Kim, et al (2007) showed fenofibrate protects endothelial cells against apoptosis via a PPARα independent, AMPK dependent activation. Although the latter study used a similar concentration of fenofibrate (50μM) compared to ours, it was performed in retinal endothelial cells and treatment lasted for 1 hour.…”

Section: Discussionmentioning

confidence: 99%