Subcellular Reactive Oxygen Species (ROS) in Cardiovascular Pathophysiology

Overview

Journal Antioxidants (Basel)

Date 2018 Jan 17

PMID 29337890

Citations 48

Authors

Sarah Aldosari

Maan Awad

Elizabeth O Harrington

Frank W Sellke

M Ruhul Abid

Affiliations

Soon will be listed here.

Abstract

There exist two opposing perspectives regarding reactive oxygen species (ROS) and their roles in angiogenesis and cardiovascular system, one that favors harmful and causal effects of ROS, while the other supports beneficial effects. Recent studies have shown that interaction between ROS in different sub-cellular compartments plays a crucial role in determining the outcomes (beneficial vs. deleterious) of ROS exposures on the vascular system. Oxidant radicals in one cellular organelle can affect the ROS content and function in other sub-cellular compartments in endothelial cells (ECs). In this review, we will focus on a critical fact that the effects or the final phenotypic outcome of ROS exposure to EC are tissue- or organ-specific, and depend on the spatial (subcellular localization) and temporal (duration of ROS exposure) modulation of ROS levels.

Citing Articles

Modulating the Biliverdin Reductase (BVR)/ERK1/2 Axis to Attenuate Oxidative Stress in Rat Arterial Rings.

Sharma K, Sterle M, Mozina H Iran J Pharm Res. 2025; 23(1):e156828.

PMID: 40066119 PMC: 11892756. DOI: 10.5812/ijpr-156828.

Mitochondrial Peroxiredoxins and Monoamine Oxidase-A: Dynamic Regulators of ROS Signaling in Cardioprotection.

Ferko M, Alanova P, Janko D, Opletalova B, Andelova N Physiol Res. 2025; 73(6):887-900.

PMID: 39903882 PMC: 11835206.

Hypoxia-Induced Mitochondrial ROS and Function in Pulmonary Arterial Endothelial Cells.

Wang H, Song T, Reyes-Garcia J, Wang Y Cells. 2024; 13(21.

PMID: 39513914 PMC: 11545379. DOI: 10.3390/cells13211807.

Childhood Cardiovascular Health, Obesity, and Some Related Disorders: Insights into Chronic Inflammation and Oxidative Stress.

Hertis Petek T, Marcun Varda N Int J Mol Sci. 2024; 25(17).

PMID: 39273654 PMC: 11396019. DOI: 10.3390/ijms25179706.

The relationship of redox signaling with the risk for atherosclerosis.

Lei S, Liu C, Zheng T, Fu W, Huang M Front Pharmacol. 2024; 15:1430293.

PMID: 39148537 PMC: 11324460. DOI: 10.3389/fphar.2024.1430293.

References

Natarajan R, Salloum F, Fisher B, Kukreja R, Fowler 3rd A . Hypoxia inducible factor-1 activation by prolyl 4-hydroxylase-2 gene silencing attenuates myocardial ischemia reperfusion injury. Circ Res. 2005; 98(1):133-40. DOI: 10.1161/01.RES.0000197816.63513.27. View

Dikalova A, Bikineyeva A, Budzyn K, Nazarewicz R, McCann L, Lewis W . Therapeutic targeting of mitochondrial superoxide in hypertension. Circ Res. 2010; 107(1):106-16. PMC: 2901409. DOI: 10.1161/CIRCRESAHA.109.214601. View

Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T . Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation. 2001; 104(22):2673-8. DOI: 10.1161/hc4601.099485. View

Dikalov S, Nazarewicz R, Bikineyeva A, Hilenski L, Lassegue B, Griendling K . Nox2-induced production of mitochondrial superoxide in angiotensin II-mediated endothelial oxidative stress and hypertension. Antioxid Redox Signal. 2013; 20(2):281-94. PMC: 3887459. DOI: 10.1089/ars.2012.4918. View

Thu V, Kim H, Ha S, Yoo J, Park W, Kim N . Glutathione peroxidase 1 protects mitochondria against hypoxia/reoxygenation damage in mouse hearts. Pflugers Arch. 2010; 460(1):55-68. DOI: 10.1007/s00424-010-0811-7. View

Kim Y, Kim S, Tatsunami R, Yamamura H, Fukai T, Ushio-Fukai M . ROS-induced ROS release orchestrated by Nox4, Nox2, and mitochondria in VEGF signaling and angiogenesis. Am J Physiol Cell Physiol. 2017; 312(6):C749-C764. PMC: 5494593. DOI: 10.1152/ajpcell.00346.2016. View

Bendall J, Rinze R, Adlam D, Tatham A, De Bono J, Wilson N . Endothelial Nox2 overexpression potentiates vascular oxidative stress and hemodynamic response to angiotensin II: studies in endothelial-targeted Nox2 transgenic mice. Circ Res. 2007; 100(7):1016-25. DOI: 10.1161/01.RES.0000263381.83835.7b. View

Abid M, Kachra Z, Spokes K, Aird W . NADPH oxidase activity is required for endothelial cell proliferation and migration. FEBS Lett. 2000; 486(3):252-6. DOI: 10.1016/s0014-5793(00)02305-x. View

Evangelista A, Thompson M, Bolotina V, Tong X, Cohen R . Nox4- and Nox2-dependent oxidant production is required for VEGF-induced SERCA cysteine-674 S-glutathiolation and endothelial cell migration. Free Radic Biol Med. 2012; 53(12):2327-34. PMC: 3568680. DOI: 10.1016/j.freeradbiomed.2012.10.546. View

10.

Feng J, Damrauer S, Lee M, Sellke F, Ferran C, Abid M . Endothelium-dependent coronary vasodilatation requires NADPH oxidase-derived reactive oxygen species. Arterioscler Thromb Vasc Biol. 2010; 30(9):1703-10. PMC: 2924465. DOI: 10.1161/ATVBAHA.110.209726. View

11.

Abid M, Spokes K, Shih S, Aird W . NADPH oxidase activity selectively modulates vascular endothelial growth factor signaling pathways. J Biol Chem. 2007; 282(48):35373-85. DOI: 10.1074/jbc.M702175200. View

12.

Ray R, Murdoch C, Wang M, Santos C, Zhang M, Alom-Ruiz S . Endothelial Nox4 NADPH oxidase enhances vasodilatation and reduces blood pressure in vivo. Arterioscler Thromb Vasc Biol. 2011; 31(6):1368-76. DOI: 10.1161/ATVBAHA.110.219238. View

13.

Datla S, Peshavariya H, Dusting G, Mahadev K, Goldstein B, Jiang F . Important role of Nox4 type NADPH oxidase in angiogenic responses in human microvascular endothelial cells in vitro. Arterioscler Thromb Vasc Biol. 2007; 27(11):2319-24. DOI: 10.1161/ATVBAHA.107.149450. View

14.

Martin-Padura I, de Nigris F, Migliaccio E, Mansueto G, Minardi S, Rienzo M . p66Shc deletion confers vascular protection in advanced atherosclerosis in hypercholesterolemic apolipoprotein E knockout mice. Endothelium. 2008; 15(5-6):276-87. DOI: 10.1080/10623320802487791. View

15.

Azumi H, Inoue N, Ohashi Y, Terashima M, Mori T, Fujita H . Superoxide generation in directional coronary atherectomy specimens of patients with angina pectoris: important role of NAD(P)H oxidase. Arterioscler Thromb Vasc Biol. 2002; 22(11):1838-44. DOI: 10.1161/01.atv.0000037101.40667.62. View

16.

Doughan A, Harrison D, Dikalov S . Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction. Circ Res. 2007; 102(4):488-96. DOI: 10.1161/CIRCRESAHA.107.162800. View

17.

Schroder K, Zhang M, Benkhoff S, Mieth A, Pliquett R, Kosowski J . Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase. Circ Res. 2012; 110(9):1217-25. DOI: 10.1161/CIRCRESAHA.112.267054. View

18.

Shafique E, Torina A, Reichert K, Colantuono B, Nur N, Ravichandran V . Mitochondrial redox plays a critical role in the paradoxical effects of NAPDH oxidase-derived ROS on coronary endothelium. Cardiovasc Res. 2017; 113(2):234-246. PMC: 5340144. DOI: 10.1093/cvr/cvw249. View

19.

Madamanchi N, Runge M . Redox signaling in cardiovascular health and disease. Free Radic Biol Med. 2013; 61:473-501. PMC: 3883979. DOI: 10.1016/j.freeradbiomed.2013.04.001. View

20.

Abid M, Sellke F . Antioxidant Therapy: Is it your Gateway to Improved Cardiovascular Health?. Pharm Anal Acta. 2015; 6(1). PMC: 4439011. DOI: 10.4172/2153-2435.1000323. View