Abstract
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.
Highlights
Senescence marker protein-30 (SMP30), a 34-kDa protein, is a novel molecule whose expression decreases with age in a sex-independent manner
We have reported that superoxide is produced by cardiac myocytes in proportion to cardiac metabolism, which leads to the production of vasoactive hydrogen peroxide (H2O2) [9]
We measured the generation of H2O2 and superoxide in cardiac myocytes of SMP30 KO mice and the change in coronary arterial tone induced by myocyte metabolites
Summary
Senescence marker protein-30 (SMP30), a 34-kDa protein, is a novel molecule whose expression decreases with age in a sex-independent manner. We have adopted a procedure using isolated cardiac myocytes and single arterioles to evaluate the specific effect of metabolic regulation on the coronary blood-flow system [9,10,11]. Using this system, we investigated SMP30’s effect on coronary vasoactive responses to cardiac myocyte metabolites and examined the effect of myocardium-dependent regulation of coronary vascular tone in response to oxidant stress in SMP30 KO mice. We measured the generation of H2O2 and superoxide in cardiac myocytes of SMP30 KO mice and the change in coronary arterial tone induced by myocyte metabolites
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