Antioxidant Treatment Improves Cardiac Dysfunction in a Murine Model of Premature Aging.
Bmal1-(brain and muscle ARNT-like protein-1) deficient (Bmal1) mice prematurely age because of an increased reactive oxygen species (ROS) production. These mice also show a decline in cardiac function with age. We investigated whether an antioxidant treatment can ameliorate the declining cardiac function in prematurely aged Bmal1 mice. Male Bmal1 and wild-type (Bmal1) mice were exposed for 15 weeks to a high fat and high cholesterol diet with or without the antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL; 5 mmol/L; in drinking water during the last 10 weeks). Echocardiographic analysis revealed that TEMPOL treatment of Bmal1 mice normalized cardiac function, as evidenced by a decrease in left ventricular diastolic and systolic internal diameters, and by an increase in fractional shortening and ejection fraction. The antioxidant did not affect cardiac function in Bmal1 mice. Although TEMPOL did not influence cardiac ROS levels in Bmal1 mice, it significantly protected Bmal1 cardiac telomeres from oxidation, as evidenced by a reduction in the telomere damage score (0.11 ± 0.012% vs. 0.16 ± 0.015%; P = 0.028). Thus, antioxidant treatment normalized cardiac function of Bmal1 mice, probably in part by scavenging ROS.
*Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; †Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria; ‡Cardiology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; §Department of Internal Medicine, Service of Cardiology, University Hospitals Leuven, Leuven, Belgium.
Bianca
B
Hemmeryckx
Philipp
P
Hohensinner
Melissa
M
Swinnen
Ward
W
Heggermont
Johann
J
Wojta
Henri Roger
HR
Lijnen
D056930:ARNTL Transcription Factors / Q000378:metabolism*; D019588:Aging, Premature / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000009:adverse effects; D003497:Cyclic N-Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D013113:Spin Labels; D016896:Treatment Outcome
D056930:ARNTL Transcription Factors; D000975:Antioxidants; C538961:Bmal1 protein, mouse; D002791:Cholesterol, Dietary; D003497:Cyclic N-Oxides; D013113:Spin Labels; C001803:tempol