Senescence Marker Protein-30 (SMP30) Deficiency Impairs Myocardium-Induced Dilation of Coronary Arterioles Associated with Reactive Oxygen Species

International Journal of Molecular Sciences

Hiroyuki Mizukami¹  Shu-ichi Saitoh¹  Hirofumi Machii¹  Shinya Yamada¹  Yasuto Hoshino¹  Tomofumi Misaka¹  Akihito Ishigami² 

[1] Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan; E-Mails:;Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan; E-Mail:

关键词: coronary circulation;    oxidant stress;    SMP30;    cardiac myocyte;    coronary arterioles;    vasomotor tone;   

DOI  :  10.3390/ijms14059408

来源: mdpi

【 摘 要 】

Senescence marker protein-30 (SMP30) decreases with aging. Mice with SMP30 deficiency, a model of aging, have a short lifespan with increased oxidant stress. To elucidate SMP30’s effect on coronary circulation derived from myocytes, we measured the changes in the diameter of isolated coronary arterioles in wild-type (WT) mice exposed to supernatant collected from isolated paced cardiac myocytes from SMP30 KO or WT mice. Pacing increased hydrogen peroxide in myocytes, and hydrogen peroxide was greater in SMP30 KO myocytes compared to WT myocytes. Antimycin enhanced and FCCP (oxidative phosphorylation uncoupler in mitochondria) decreased superoxide production in both groups. Addition of supernatant from stimulated myocytes, either SMP30 KO or WT, caused vasodilation. The degree of the vasodilation response to supernatant was smaller in SMP30 KO mice compared to WT mice. Administration of catalase to arterioles eliminated vasodilation in myocyte supernatant of WT mice and converted vasodilation to vasoconstriction in myocyte supernatant of SMP30 KO mice. This vasoconstriction was eliminated by olmesartan, an angiotensin II receptor antagonist. Thus, SMP30 deficiency combined with oxidant stress increases angiotensin and hydrogen peroxide release from cardiac myocytes. SMP30 plays an important role in the regulation of coronary vascular tone by myocardium.

【 授权许可】

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