Age, sex, and vessel region affect the vasomotor function and gene expression signature of the aorta in mice

Abstract

Introduction Vascular aging is associated with endothelial dysfunction, changes in vascular elasticity or stiffness, and the prevalence of cardiovascular diseases. Aging differs by sex. The effects of age, sex, and vessel region on arterial vasomotor function and gene expression signatures have not been explored yet. Thus, we investigated contraction, relaxation, and endothelial integrity, as well as gene expression, in the proximal and distal segments of the thoracic aorta in 6- and 18-month-old mice. Materials and methods Male and female C57BL/6J mice at 6 (n = 11/sex) and 18 (n = 12/sex) months of age were used. Segments of the proximal and distal thoracic aorta were mounted in organ bath chambers. We assessed the maximal receptor-independent contractility using potassium chloride (KCl), endothelial integrity using phenylephrine (PE), endothelial-dependent relaxation using acetylcholine (ACh), and endothelial-independent relaxation using sodium nitroprusside (SNP). Using microarrays, we performed transcriptomics on another 6 six mice of every subgroup. Results Endothelial integrity decreases significantly with age in male mice, but only in the proximal segment. The relaxation to ACh decreases with age in both sexes in the proximal and only in female individuals in the descending segment. In females, endothelial-dependent relaxation is higher than in males, in young age, independent of the segment, and in old age, still in the proximal segment. Endothelial-independent relaxation decreases with age only in the distal segment of female subjects. Genes associated with the electron transport chain, crucial for energy production in mitochondria, are decreased by age. The G-protein coupled receptor -G13 alpha subunit- signaling pathway and proteasome degradation, which are crucial for developing and maintaining endothelial integrity, were reduced in the aorta of old mice. Genes involved in endothelial nitric oxide synthesis were especially downregulated in old male mice. Conclusion Endothelial integrity and endothelial-dependent relaxation depend on age, sex, and segment of the descending thoracic aorta in mice. Genes associated with endothelial-dependent relaxation, endothelial integrity, and vascular aging change markedly by age, including some sex- and segment-specific differences.