ABSTRACT
The contractile function of vascular smooth muscle cells (VSMCs) typically undergoes significant changes with advancing age, leading to severe vascular aging-related diseases. The precise role and mechanism of stromal interaction molecule-1 (STIM1) in age-mediated Ca2+ signaling and vasocontraction remain unclear. The connection between STIM1 and age-related vascular dysfunction was investigated using a multi-myograph system, immunohistochemical analysis, protein blotting, and SA-ß-gal staining. Results showed that vasoconstrictor responses in the thoracic aorta, intrarenal artery, and coronary artery decreased with age. STIM1 knockdown in the intrarenal and coronary arteries reduced vascular tone in young mice, while no change was observed in the thoracic aorta. A significant reduction in vascular tone occurred in the STIM1 knockout group with nifedipine. In the thoracic aorta, vasoconstriction significantly decreased with age following the use of nifedipine and thapsigargin and almost disappeared after STIM1 knockdown. The proportion of senescent VSMCs increased significantly in aged mice and further increased in sm-STIM1 KO aged mice. Moreover, the expression of senescence markers p21, p16, and IL-6 significantly increased with age, with p21 expression further increased in the STIM1 knockdown aged group, but not p16 or IL-6. These findings indicate that different arteries exhibit distinct organ-specific features and that STIM1 downregulation may contribute to age-related vasoconstrictive dysfunction through activation of the p21 pathway.
Subject(s)
Aging , Coronary Vessels , Down-Regulation , Stromal Interaction Molecule 1 , Vasoconstriction , Animals , Stromal Interaction Molecule 1/metabolism , Stromal Interaction Molecule 1/genetics , Vasoconstriction/drug effects , Mice , Coronary Vessels/metabolism , Coronary Vessels/physiopathology , Aging/metabolism , Male , Mice, Knockout , Mice, Inbred C57BL , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/drug effects , Renal Artery/metabolism , Cellular Senescence/drug effects , Interleukin-6/metabolism , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/drug effects , Aorta/metabolism , Aorta/drug effectsABSTRACT
Objective@#To understand the effect of pregnancyrelated anxiety on preschool childrens executive functions(EFs) and gender difference in order to optimize the early development environment of offspring life.@*Methods@#This study was based on the ChinaAnhui Birth Cohort Study. Pregnant women from Maternal and Child Health Care Hospital in Maanshan, Anhui province between October 2008 and October 2010 were recruited. The general information of pregnant women and the pregnancyrelated anxiety were collected prospectively in the first trimester of pregnancy. A cohort of 3 556 children aged 3-5 were followed up and their basic characteristics were collected. Executive function of preschool children was assessed by Behavior Rating Inventory of Executive FunctionPreschool Version(BRIEF) (parent version).@*Results@#In boys, compared with the control group, pregnancyrelated anxiety in the first trimester of pregnancy was associated with the risk of abnormality in working memory, planning/organization and GEC[OR(95%CI)=1.40(1.06-1.85), 1.64(1.06-2.54), 1.89(1.27-2.82)]. Anxiety in the both trimesters of pregnancy was associated with the risk of abnormality in inhibition, working memory, planning/organization and GEC[OR(95%CI)=2.60(1.45-4.67), 2.45(1.69-3.57), 2.23(1.28-3.88), 3.27(2.03-5.28)]. In girls, pregnancyrelated anxiety in the first trimester of pregnancy was associated with the risk of abnormality in inhibition and working memory[OR(95%CI)=1.79(1.13-2.83), 1.45(1.07-1.98)]. Anxiety in the third trimester of pregnancy was associated with the risk of abnormality in inhibition[OR(95%CI)=2.26(1.17-4.38)]. Anxiety in both trimesters of pregnancy was associated with the risk of abnormality in inhibition and working memory[OR(95%CI)=2.45(1.40-4.28), 2.02(1.35-3.01)].@*Conclusion@#Pregnancyrelated anxiety significantly affected the executive function of preschool children, and there was a significant doseresponse relationship. Pregnancyrelated anxiety primarily affects working memory, planning/organization and GEC function in boys, and the working memory, inhibition function in girls.