Heme oxygenase (HO)-1 induction prevents Endoplasmic Reticulum stress-mediated endothelial cell death and impaired angiogenic capacity

Abstract

Most of diabetic cardiovascular complications are attributed to endothelial dysfunction and impaired angiogenesis. Endoplasmic Reticulum (ER) and oxidative stresses were shown to play a pivotal role in the development of endothelial dysfunction in diabetes.Hemeoxygenase-1 (HO-1) was shown to protect against oxidative stress in diabetes; however, its role in alleviating ER stress-induced endothelial dysfunction remains not fully elucidated. We aim here to test the protective role of HO-1 against high glucose-mediated ER stress and endothelial dysfunction and understand the underlying mechanisms with special emphasis on oxidative stress, inflammation and cell death. Altogether, we show here the critical role of ER stress-mediated cell death in diabetesinduced endothelial dysfunction and impaired angiogenesis and underscore the role of HO-1 induction as a key therapeutic modulator for ER stress response in ischemic disorders and diabetes. Our results also highlight the complex interplay between ER stress response and oxidative stress.

C1q/TNF-Related Protein-9 Ameliorates Ox-LDL-Induced Endothelial Dysfunction via PGC-1α/AMPK-Mediated Antioxidant Enzyme Induction

“…Antioxidant enzymes including HO-1, NQO1, GCLC and GCLM are well clarified to reduce ROS production [44]. HO-1 induction is a therapeutic strategy in diabetes-induced endothelial dysfunction [45]. Cinnamaldehyde is suggested to alleviate endothelial dysfunction in response to high glucose by upregulation of NQO1 [46].…”

Trimetallic Nitride Endohedral Fullerenes Carboxyl-Gd3N@C80: A New Theranostic Agent for Combating Oxidative Stress and Resolving Inflammation

“…HO-1 is an endogenous antioxidative microsomal enzyme whose upregulation showed a protective role (such as immune-modulation) in combating oxidative stress and resolving inflammation. 24 Nrf2 is a basic leucine zipper (bZIP) protein that regulates the expression of antioxidative proteins, such as HO-1. 25 To examine the antioxidative and anti-inflammatory effect of carboxyl-Gd 3 N@C 80 , we pretreated Raw 264.7 cells with nanoparticle at 3.5 µ M for 20 h and LPS for another 4 h. Total RNA were isolated, reverse-transcribed to cDNA, and analyzed with real-time PCR.…”

Hmox1 promotes osteogenic differentiation at the expense of reduced adipogenic differentiation induced by BMP9 in C3H10T1/2 cells

“…Hmox1, the inducible form of heme oxygenase, degrades heme to three products − ferrous ions, carbon monoxide, and biliverdin. In addition to this catalytic function in heme metabolism, Hmox1 may function as a cytoprotective factor through its end‐products with antioxidant, anti‐inflammatory, anti‐apoptotic, and cell‐signaling properties . Several studies have demonstrated the tissue protective properties of Hmox1 in mouse and rat models of cardiovascular, pulmonary, kidney, gastrointestinal, brain or skin injury, and disease .…”