Mitochondrial Mechanisms of Oxidative Stress and Endothelial Dysfunction

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 8295

Special Issue Editors


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Guest Editor
Laboratory of Cellular Metabolism, Nencki Institute of Experimental Biology PAS, 02-093 Warsaw, Poland
Interests: cell metabolism; endothelial physiology and dysfunction; mitochondrial role in response to stress; bioenergetics; mitochondrial network architecture, oxidative stress; inflammatory response; intercellular communication; prosurvival cell response to stress

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Guest Editor
Laboratory of Cellular Metabolism, Nencki Institute of Experimental Biology PAS, 02-093 Warsaw, Poland
Interests: metabolism; mitochondria; bioenergetics; calcium signaling; vascular endothelium; muscle differentiation
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Special Issue Information

Dear Colleagues,

The vascular endothelium is a metabolically active tissue that produces and secretes a number of factors responsible for the regulation of blood vessel relaxation/constriction processes. In the endothelium, the oxidative stress that accompanies metabolic defects in a variety of cells affects vascular tone by reducing NO bioavailability. Among the several sources of cellular ROS, the mitochondrial respiratory chain and NAD(P)H oxidase play leading roles. Mitochondria are the main source of ATP in the vast majority of mammalian cells, but in the endothelial ones, ATP is mainly delivered by glycolysis, while the mitochondria have a role in the regulation of cellular signaling, particularly as a source of reactive oxygen species and in the dynamic buffering of calcium ions. Consequently, they modulate NO generation and inflammatory responses, which are among the most critical functions of the endothelium. Therefore, mitochondrial stress or disturbances in mitochondrial metabolism, which often result in excessive ROS generation, may lead to endothelial dysfunction, vascular abnormalities and, eventually, cardiovascular diseases.

This Special Issue aims to gather original research articles and review articles focusing on the mitochondrial mechanisms involved in the response to stress stimuli and the development and progression of a number of pathologies including endothelial dysfunction.

Dr. Dorota Dymkowska
Prof. Dr. Krzysztof Zabłocki
Guest Editors

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Keywords

  • mitochondrial metabolism
  • reactive oxygen species
  • oxidative stress
  • mitochondrial response to stress stimuli
  • inflammatory response
  • endothelial mitochondria
  • endothelial dysfunction
  • cardiovascular diseases

Published Papers (3 papers)

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Research

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22 pages, 5437 KiB  
Article
Alterations in Energy Metabolism, Mitochondrial Function and Redox Homeostasis in GK Diabetic Rat Tissues Treated with Aspirin
by Annie John, Layla Amiri, Jasmin Shafarin, Saeed Tariq, Ernest Adeghate, Frank Christopher Howarth and Haider Raza
Life 2022, 12(1), 104; https://doi.org/10.3390/life12010104 - 12 Jan 2022
Cited by 4 | Viewed by 2360
Abstract
Our recent studies have demonstrated that aspirin treatment prevents inflammatory and oxidative stress-induced alterations in mitochondrial function, improves glucose tolerance and pancreatic endocrine function and preserves tissue-specific glutathione (GSH)-dependent redox homeostasis in Goto-Kakizaki (GK) diabetic rats. In the current study, we have investigated [...] Read more.
Our recent studies have demonstrated that aspirin treatment prevents inflammatory and oxidative stress-induced alterations in mitochondrial function, improves glucose tolerance and pancreatic endocrine function and preserves tissue-specific glutathione (GSH)-dependent redox homeostasis in Goto-Kakizaki (GK) diabetic rats. In the current study, we have investigated the mechanism of action of aspirin in maintaining mitochondrial bioenergetics and redox metabolism in the liver and kidneys of GK rats. Aspirin reduced the production of reactive oxygen species (ROS) and oxidative stress-induced changes in GSH metabolism. Aspirin treatment also improved mitochondrial respiratory function and energy metabolism, in addition to regulating the expression of cell signaling proteins that were altered in diabetic animals. Ultrastructural electron microscopy studies revealed decreased accumulation of glycogen in the liver of aspirin-treated diabetic rats. Hypertrophic podocytes with irregular fusion of foot processes in the renal glomerulus and detached microvilli, condensed nuclei and degenerated mitochondria observed in the proximal convoluted tubules of GK rats were partially restored by aspirin. These results provide additional evidence to support our previous observation of moderation of diabetic complications by aspirin treatment in GK rats and may have implications for cautious use of aspirin in the therapeutic management of diabetes. Full article
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16 pages, 1737 KiB  
Article
Effect of Aspirin on Mitochondrial Dysfunction and Stress in the Pancreas and Heart of Goto-Kakizaki Diabetic Rats
by Annie John, Layla Amiri, Jasmin Shafarin, Frank Christopher Howarth and Haider Raza
Life 2021, 11(9), 902; https://doi.org/10.3390/life11090902 - 30 Aug 2021
Cited by 5 | Viewed by 2820
Abstract
Our previous study in Goto-Kakizaki (GK) type 2 diabetic rats provided significant evidence that aspirin treatment improves pancreatic β-cell function by reducing inflammatory responses and improving glucose tolerance. In the present study, we aimed to elucidate the mechanism of action of aspirin on [...] Read more.
Our previous study in Goto-Kakizaki (GK) type 2 diabetic rats provided significant evidence that aspirin treatment improves pancreatic β-cell function by reducing inflammatory responses and improving glucose tolerance. In the present study, we aimed to elucidate the mechanism of action of aspirin on the pathophysiology and progression of type 2 diabetic complications in the heart and pancreas of insulin-resistant GK rats. Aspirin treatment demonstrated a reduction in mitochondrial reactive oxygen species (ROS) production and lipid peroxidation, accompanied by improved redox homeostasis. Furthermore, the recovery of metabolic and mitochondrial functions, as well as cytochrome P450 enzyme activities, which were altered in the pancreas and heart of GK rats, were observed. Aspirin treatment brought the activity of CYP 2E1 to the control level in both tissues, whereas the CYP 3A4 level decreased only in the pancreas. This suggests the tissue-specific differential metabolism of substrates in these rats. The recovery of redox homeostasis could be the key target in the improvement of oxidative-stress-dependent alterations in mitochondrial functions which, in turn, facilitated improved energy metabolism in these tissues in the aspirin-treated GK rats. These results may have implications in determining the therapeutic use of aspirin, either alone or in combination with other clinically approved therapies, in insulin-resistant type 2 diabetes. Full article
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Review

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13 pages, 866 KiB  
Review
Salvia miltiorrhiza Protects Endothelial Dysfunction against Mitochondrial Oxidative Stress
by Yu-Chen Cheng, I-Ling Hung, Yen-Nung Liao, Wen-Long Hu and Yu-Chiang Hung
Life 2021, 11(11), 1257; https://doi.org/10.3390/life11111257 - 18 Nov 2021
Cited by 7 | Viewed by 2256
Abstract
Salvia miltiorrhiza (SM) is a common traditional Chinese medicine used in the treatment of cardiovascular and cerebrovascular diseases. Endothelial dysfunction plays an important role in the pathology of cardiovascular diseases. Endothelial dysfunction may induce inflammation and change vascular tone and permeability. The main [...] Read more.
Salvia miltiorrhiza (SM) is a common traditional Chinese medicine used in the treatment of cardiovascular and cerebrovascular diseases. Endothelial dysfunction plays an important role in the pathology of cardiovascular diseases. Endothelial dysfunction may induce inflammation and change vascular tone and permeability. The main pathological mechanism of endothelial dysfunction is the formation of reactive oxygen species (ROS). Mitochondria are the main source of energy and can also produce large amounts of ROS. Recent studies have shown that extracts of SM have antioxidative, anti-inflammatory, and antithrombus properties. In this review, we discuss the mechanism of oxidative stress in the mitochondria, endothelial dysfunction, and the role of SM in these oxidative events. Full article
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