Mechanism Of Aerobic Exercise Improving SOCE Mediated Coronary Systolic Function In Aging Rats

Objective:Studies have shown that aging can cause variation in vasoconstriction function in elderly rats.Store-operated Ca²⁺entry（SOCE）and its constituent protein Orai and STIM are important in vasoconstriction.In this paper,which was to explore the effects of aerobic exercise on SOCE-mediated coronary systolic function in elderly rats.The miRNAs that may participate in SOCE mediated coronary systolic function were screened by transcriptome sequencing technology to explore the possible mechanism of aerobic exercise regulating aging vascular systolic function.Methods:Ten young rats were set as the Young group;Twenty aging rats were randomly divided into the Old group and Old exercise group,each group with ten rats.The elderly exercise rats received 11 weeks of treadmill aerobic exercise intervention.Making coronary arteries into vascular rings for tension measurement.The SOCE mediated coronary artery contraction of rats in each group was detected.The expressions of Orai and STIM in the coronary smooth muscle of three groups were detected by the immunohistochemical method.High throughput sequencing of rat serum was executed to screen miRNAs that may be related to SOCE mediated coronary contraction.Results:（1）There was no significant difference in the vasoconstriction induced by high potassium solution among three group（P>0.05）.（2）In the vasoconstriction induced by endothelin-1,compared with the Young group,there was significantly enhanced of the coronary artery contraction in the Old group（P<0.05）;compared with the Old group,the coronary artery contraction in the Old+ET group was significantly decreased（P<0.05）;there was no significant difference in vasoconstriction between the Young group and the Old+ET group（P>0.05）.It suggested that the vasoconstriction of the elderly group was enhanced,and exercise could attenuate the vasoconstriction caused by endothelin-1.（3）In the experiment of SOCE-related coronary contraction induced by endothelin-1,the coronary contraction in Old group was significantly higher than the Young group（P<0.05）,and that in Old+ET group was significantly lower than that in Old group（P<0.05）.There was no significant difference between Old+ET group and Young group.It is suggested that aging weakens the coronary vasodilation effect regulated by SOCE,which leads to the enhancement of contraction,while aerobic exercise up-regulates the relaxation effect regulated by SOCE,which can restore the contraction to the level of the young group.（4）The expression and distribution of Orai and STIM in each group were observed by immunohistochemistry.The expression of Orai1 in myocardium was abundant in the three groups,while the expression in coronary smooth muscle was lower.The expression of Orai2 was abundant in myocardium and coronary smooth muscle layer.Compared with Young group,the expression of Orai2 protein in Old group and Old+ET group was significantly lower,and Old+ET group was significantly lower than that in Old group.The expression of Orai3 was abundant in myocardium and coronary artery smooth muscle layer,the expression of Orai3protein in Old group was significantly lower than that in Young group,and the expression of Orai3 in Old+ET group was higher than that in Old group,but there was no significant difference between Young group and Old+ET group.The expression of STIM1 was abundant in myocardium and coronary artery smooth muscle layer,and the expression of STIM1 in Old group and Old+ET group was significantly lower than that in Young group,and the expression of STIM1 in Old+ET group was higher than that in Old group.The expression of STIM2 in the smooth muscle layer of coronary artery was low.（5）All differentially expressed miRNAs had found 114 Different expressions of miRNAs,rno-miR-298-5p was the target miRNA of Orai2;novel＿miR＿1079 was the target miRNA of STIM1;rno-miR-27a-5p was the target miRNA of STIM2 and Orai3.Conclusion:（1）Aerobic exercise can effectively improve the abnormal enhancement of coronary artery contraction induced by aging,which is related to the down-regulation of SOCE-related proteins Orai and STIM.The mechanism may be through miRNA to regulate the expression of Orai and STIM,thus improving coronary function.Among them,rno-Mir-298-5p,rno-Mir-27a-5p and novel＿miR＿1079 are potential target miRNAs.