p53 plays a crucial role in endothelial dysfunction associated with hyperglycemia and ischemia

Journal of Molecular and Cellular Cardiology
Masataka YokoyamaTohru Minamino

Abstract

p53 is a guardian of the genome that protects against carcinogenesis. There is accumulating evidence that p53 is activated with aging. Such activation has been reported to contribute to various age-associated pathologies, but its role in vascular dysfunction is largely unknown. The aim of this study was to investigate whether activation of endothelial p53 has a pathological effect in relation to endothelial function. We established endothelial p53 loss-of-function and gain-of-function models by breeding endothelial-cell specific Cre mice with floxed Trp53 or floxed Mdm2/Mdm4 mice, respectively. Then we induced diabetes by injection of streptozotocin. In the diabetic state, endothelial p53 expression was markedly up-regulated and endothelium-dependent vasodilatation was significantly impaired. Impairment of vasodilatation was significantly ameliorated in endothelial p53 knockout (EC-p53 KO) mice, and deletion of endothelial p53 also significantly enhanced the induction of angiogenesis by ischemia. Conversely, activation of endothelial p53 by deleting Mdm2/Mdm4 reduced both endothelium-dependent vasodilatation and ischemia-induced angiogenesis. Introduction of p53 into human endothelial cells up-regulated the expression of phosph...Continue Reading

Citations

Jul 7, 2020·Journal of Cellular and Molecular Medicine·Junduo WuHao Wu
Mar 13, 2020·Basic & Clinical Pharmacology & Toxicology·Sara I Graves, Darren J Baker
Jan 11, 2020·Frontiers in Physiology·Jacopo SabbatinelliAngelica Giuliani
Jan 11, 2020·Frontiers in Cell and Developmental Biology·Brian Lam, Emilie Roudier
Aug 22, 2020·Journal of Lipid and Atherosclerosis·Ippei Shimizu, Tohru Minamino
Feb 18, 2021·World Journal of Diabetes·Er-Fei LuoDong Wang
Jan 26, 2021·Frontiers in Cardiovascular Medicine·Clément MercierPedro Geraldes
May 29, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pamela Di TomoAssunta Pandolfi
Jul 14, 2021·Phlebology·Mohamad Hadi Saeed ModagheghMohammad Mahdi Kamyar

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aging & Diabetes

This feed focuses on the role of the aging process on developing diabetes.

Aging-Associated Metabolic Disorders

Age is associated with many metabolic disorders including cardiovascular diseases, type 2 diabetes, stroke and heart disease. The mediators in aging process have been suggested to play a part in the cellular processes responsible for these metabolic disorders. Here is the latest research on aging-associated metabolic disorders.