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Deficiency in gp91Phox (NOX2) Protects against Oxidative Stress and Cardiac Dysfunction in Iron Overloaded Mice

1
Department of Biochemistry and Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037, USA
2
Division of Cardiology, Children’s National Medical Center, Washington, DC 20010, USA
*
Authors to whom correspondence should be addressed.
Received: 27 August 2020 / Revised: 11 September 2020 / Accepted: 14 September 2020 / Published: 15 September 2020
(This article belongs to the Special Issue Nutrient Deficiency and Drug Induced Cardiac Injury and Dysfunction)
The role of NADPH oxidase subunit, gp91phox (NOX2) in development of oxidative stress and cardiac dysfunction due to iron (Fe)-overload was assessed. Control (C57BL/6J) and gp91phox knockout (KO) mice were treated for up to 8 weeks with Fe (2.5 mg/g/wk, i.p.) or Na-dextran; echocardiography, plasma 8-isoprostane (lipid peroxidation marker), cardiac Fe accumulation (Perl’s staining), and CD11b+ (WBCs) infiltrates were assessed. Fe caused no adverse effects on cardiac function at 3 weeks. At 6 weeks, significant declines in left ventricular (LV) ejection fraction (14.6% lower), and fractional shortening (19.6% lower) occurred in the Fe-treated control, but not in KO. Prolonging Fe treatment (8 weeks) maintained the depressed LV systolic function with a trend towards diastolic dysfunction (15.2% lower mitral valve E/A ratio) in controls but produced no impact on the KO. Fe-treatment (8 weeks) caused comparable cardiac Fe accumulation in both strains, but a 3.3-fold elevated plasma 8-isoprostane, and heightened CD11b+ staining in controls. In KO mice, lipid peroxidation and CD11b+ infiltration were 50% and 68% lower, respectively. Thus, gp91phox KO mice were significantly protected against oxidative stress, and systolic and diastolic dysfunction, supporting an important role of NOX2-mediated oxidative stress in causing cardiac dysfunction during Fe overload. View Full-Text
Keywords: NOX2 knockout mice; iron overload; in situ cardiac function; oxidative stress; cardiac iron; cardiac inflammation NOX2 knockout mice; iron overload; in situ cardiac function; oxidative stress; cardiac iron; cardiac inflammation
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MDPI and ACS Style

Mak, I.T.; Kramer, J.H.; Iantorno, M.; Chmielinska, J.J.; Weglicki, W.B.; Spurney, C.F. Deficiency in gp91Phox (NOX2) Protects against Oxidative Stress and Cardiac Dysfunction in Iron Overloaded Mice. Hearts 2020, 1, 117-125. https://0-doi-org.brum.beds.ac.uk/10.3390/hearts1020012

AMA Style

Mak IT, Kramer JH, Iantorno M, Chmielinska JJ, Weglicki WB, Spurney CF. Deficiency in gp91Phox (NOX2) Protects against Oxidative Stress and Cardiac Dysfunction in Iron Overloaded Mice. Hearts. 2020; 1(2):117-125. https://0-doi-org.brum.beds.ac.uk/10.3390/hearts1020012

Chicago/Turabian Style

Mak, I. T.; Kramer, Jay H.; Iantorno, Micaela; Chmielinska, Joanna J.; Weglicki, William B.; Spurney, Christopher F. 2020. "Deficiency in gp91Phox (NOX2) Protects against Oxidative Stress and Cardiac Dysfunction in Iron Overloaded Mice" Hearts 1, no. 2: 117-125. https://0-doi-org.brum.beds.ac.uk/10.3390/hearts1020012

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