Ozone Inhalation Impairs Coronary Artery Dilation via Intracellular Oxidative Stress: Evidence for Serum-Borne Factors as Drivers of Systemic Toxicity

Abstract Background Voltage-gated K+ (Kv) channels in coronary artery smooth muscle cells (CSMCs), especially the major specific Kv1 subfamily, contribute to coronary artery vasodilation. Advanced glycation end products (AGEs) have been strongly implicated in diabetes-related cardiovascular complications. Our previous study showed AGEs can impair Kv channel-mediated coronary vasodilation by reducing Kv channel activity. However, its underlying mechanism remains unclear. Purpose Here, we used isolated rat small coronary arteries (RSCAs) and primary CSMCs to investigate the effect of AGEs on Kv channel-mediated coronary vasodilation and the possible involvement of peroxisome proliferators-activated receptor (PPAR)-γ pathway. Methods RSCAs and primary CSMCs were isolated, cultured and treated with bovine serum albumin (BSA), AGE-BSA, alagrebrium (ALA, AGE cross-linking breaker), pioglitazone (PIO) and/or GW9662, and then divided into the following groups: DMEM, BSA, AGE, AGE+ALA, AGE+PIO, and AGE+PIO+GW9662. Kv channel-mediated coronary vasodilation was analyzed using wire myograph. Histology and immunohistochemistry of RSCAs were performed. Western blot was used to detect the protein expression of RAGE, the major Kv1 channel subunits expressed in CSMCs (Kv1.2/1.5), PPAR-γ, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-2 (NOX-2). Results AGEs markedly reduced forskolin-induced Kv channel-mediated vasodilation of RSCAs by interacting with the receptor for AGEs (RAGE), and ALA or PIO significantly reversed this effect. In both RSCAs and primary CSMCs, AGEs decreased Kv1.2 and Kv1.5 channel protein expression, inhibited PPAR-γ expression, increased RAGE and NOX-2 expression. Treatment with ALA or PIO partially reversed the effects of AGEs on Kv1.2/Kv1.5 expression, accompanied by elevation of PPAR-γ level and diminished oxidative stress. Conclusion AGE/RAGE axis-induced inhibition of PPAR-γ pathway and enhancement of oxidative stress may contribute to AGEs-mediated Kv channel dysfunction and coronary vasodilation in RSCAs. Our results may provide new insights into developing therapeutic strategies to manage diabetic vasculature. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China; Natural Science Foundation of Beijing (7172059)

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Melatonin Promotes In Vitro Maturation of Vitrified-Warmed Mouse Germinal Vesicle Oocytes, Potentially by Reducing Oxidative Stress through the Nrf2 Pathway

Animals ◽

10.3390/ani11082324 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2324

Author(s):

Shichao Guo ◽

Jinyu Yang ◽

Jianpeng Qin ◽

Izhar Hyder Qazi ◽

Bo Pan ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

In Vitro Maturation ◽

Germinal Vesicle ◽

Melatonin Receptors ◽

Development Rates ◽

Nrf2 Signaling Pathway ◽

Mouse Gv Oocytes ◽

Intracellular Oxidative Stress

Previously it was reported that melatonin could mitigate oxidative stress caused by oocyte cryopreservation; however, the underlying molecular mechanisms which cause this remain unclear. The objective was to explore whether melatonin could reduce oxidative stress during in vitro maturation of vitrified-warmed mouse germinal vesicle (GV) oocytes through the Nrf2 signaling pathway or its receptors. During in vitro maturation of vitrified-warmed mouse GV oocytes, there were decreases (p < 0.05) in the development rates of metaphase I (MI) oocytes and metaphase II (MII) and spindle morphology grades; increases (p < 0.05) in the reactive oxygen species (ROS) levels; and decreases (p < 0.05) in expressions of Nrf2 signaling pathway-related genes (Nrf2, SOD1) and proteins (Nrf2, HO-1). However, adding 10−7 mol/L melatonin to both the warming solution and maturation solutions improved (p < 0.05) these indicators. When the Nrf2 protein was specifically inhibited by Brusatol, melatonin did not increase development rates, spindle morphology grades, genes, or protein expressions, nor did it reduce vitrification-induced intracellular oxidative stress in GV oocytes during in vitro maturation. In addition, when melatonin receptors were inhibited by luzindole, the ability of melatonin to scavenge intracellular ROS was decreased, and the expressions of genes (Nrf2, SOD1) and proteins (Nrf2, HO-1) were not restored to control levels. Therefore, we concluded that 10−7 mol/L melatonin acted on the Nrf2 signaling pathway through its receptors to regulate the expression of genes (Nrf2, SOD1) and proteins (Nrf2, HO-1), and mitigate intracellular oxidative stress, thereby enhancing in vitro development of vitrified-warmed mouse GV oocytes.

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Highly sensitive real-time detection of intracellular oxidative stress and application in mycotoxin toxicity evaluation based on living single-cell electrochemical sensors

The Analyst ◽

10.1039/d0an02015j ◽

2021 ◽

Author(s):

Lu Gao ◽

Jiadi Sun ◽

Liping Wang ◽

Qigao Fan ◽

Gaowen Zhu ◽

...

Keyword(s):

Oxidative Stress ◽

Electrochemical Sensor ◽

Single Cell ◽

Real Time ◽

Electrochemical Sensors ◽

Living Cells ◽

Selective Detection ◽

Toxicity Evaluation ◽

Highly Sensitive ◽

Intracellular Oxidative Stress

Single-cell electrochemical sensor is used in the local selective detection of living cells because of its high spatial–temporal resolution and sensitivity, as well as its ability to obtain comprehensive cellular physiological states and processes.

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Glaucocalyxin A inhibits hydrogen peroxide‐induced oxidative stress and inflammatory response in coronary artery smooth muscle cells

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/1440-1681.13253 ◽

2020 ◽

Vol 47 (5) ◽

pp. 765-770

Author(s):

Shunming Zhu ◽

Junbo Zhang ◽

Ying Lv

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Smooth Muscle ◽

Coronary Artery ◽

Inflammatory Response ◽

Smooth Muscle Cells ◽

Muscle Cells

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Oxidative stress as a predictor of cardiovascular events in coronary artery disease patients

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2011-0919 ◽

2012 ◽

Vol 50 (8) ◽

Cited By ~ 33

Author(s):

Cristina Vassalle ◽

Sara Bianchi ◽

Fabrizio Bianchi ◽

Patrizia Landi ◽

Debora Battaglia ◽

...

Keyword(s):

Oxidative Stress ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiovascular Events ◽

Artery Disease

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Leucocyte-depleted cardioplegia does not reduce reperfusion injury in hypothermic coronary artery bypass surgery

Perfusion ◽

10.1177/026765919901400509 ◽

1999 ◽

Vol 14 (5) ◽

pp. 371-377 ◽

Cited By ~ 11

Author(s):

P G Browning ◽

M Pullan ◽

M Jackson ◽

A Rashid

Keyword(s):

Oxidative Stress ◽

Coronary Artery ◽

Coronary Artery Bypass ◽

Coronary Artery Bypass Surgery ◽

Myocardial Injury ◽

Bypass Surgery ◽

Troponin T ◽

Artery Bypass ◽

Oxidized Glutathione ◽

Patient Groups

This study investigated the effects of leucocyte-depleted cardioplegia on postreperfusion oxidative stress and myocardial injury in elective hypothermic coronary artery bypass surgery. Forty patients were randomized to receive either cardioplegia with leucocytes depleted by an in-line Pall BC1B filter, or blood cardioplegia without leucocyte depletion. Transmyocardial oxidative stress was assessed by oxidized glutathione measurements in samples taken simultaneously from the coronary sinus and aortic root, and myocardial injury by postoperative CKMB and troponin-T measurements. The BC1B filters reduced numbers of cardioplegia leucocytes by a mean of 90.7%. Both patient groups demonstrated significant increases ( p < 0.001) in transcardiac oxidized glutathione gradients after crossclamp release. No significant differences were found between the groups for postreperfusion oxidized glutathione gradients, postoperative levels of CKMB or troponin-T, or in the frequency of perioperative and postoperative complications. These results suggest that leucocyte-depleted cardioplegia does not significantly improve myocardial protection in patients undergoing elective coronary artery bypass surgery.

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