Regional Heterogeneity of Aortic Histology and Transcriptomes In Young Cynomolgus Monkeys

BackgroundThe regional heterogeneity of vascular components is an important determinant of aortic biology. This notion has been explored in multiple mouse studies, but not in human aortas due to the difficulty of acquiring normal tissues. In the present study, we examined the regional heterogeneity of aortas in healthy non-human primates that have similarities to humans.MethodsAortic samples were harvested from the ascending, descending, suprarenal, and infrarenal regions of young cynomolgus monkeys. The regional heterogeneity of aortic structure and transcriptomes were examined by histological and bulk RNA sequencing analyses.ResultsImmunostaining of CD31 and αSMA revealed that endothelial and smooth muscle cells were distributed homogeneously across the aortic regions. In contrast, elastic fibers were less abundant and disorganized in the infrarenal aorta compared to other regions. Bulk RNA sequencing identified differences in collagen mRNA abundance among the regions.COL1A1, a major collagen gene, was highly abundant in the infrarenal aorta. Movat’s staining revealed consistently that collagen fibers were more abundant in the media and adventitia of the infrarenal aorta than in other regions. Proteoglycan accumulated in the intima of the infrarenal region. Polarized imaging of picrosirius red staining demonstrated that type 1 collagen was distributed predominantly in the adventitia and media of the infrarenal aorta adjacent to disarrayed elastic fibers. Immunostaining of COL1A1 verified type 1 collagen in the intima and adventitia close to the elastic fiber disruption.ConclusionsAortas of young cynomolgus monkeys display regional heterogeneity of its transcriptome and the structure of elastin and collagens. Elastic fibers in the infrarenal aorta are disarrayed along with the deposition of collagen fibers and proteoglycan.HIGHLIGHTS-The present study determined the regional heterogeneity of aortic biology in aortas of young cynomolgus monkeys.-Aortas of young cynomolgus monkeys displayed region-specific aortic structure and transcriptomes.-Elastic fibers are disarrayed in the infrarenal aorta along with the deposition of collagen fibers and proteoglycan.GRAPHIC ABSTRACT