Gene expression in the cardiovascular system of the domestic sheep (Ovis aries); a new tool to advance our understanding of cardiovascular disease

Abstract

Large animal models are of increasing importance in cardiovascular disease research as they demonstrate more similar cardiovascular features (in terms of anatomy, physiology and size) to humans than do rodent species. The maintenance of a healthy cardiovascular system requires expression of genes that contribute to essential biological activities and repression of those that are associated with functions likely to be detrimental to cardiovascular homeostasis. In this study we have used the transcriptome of the sheep, which has been utilised extensively to model human physiology and disease, to explore genes implicated in the process of vascular calcification. Vascular calcification is a major disruption to cardiovascular homeostasis where tissues of the cardiovascular system undergo ectopic calcification and consequent dysfunction. We investigate the gene expression profiles of genes involved in vascular calcification in a wide array of cardiovascular tissues and across multiple developmental stages, using RT-qPCR. The majority of transcriptomic studies on the mammalian cardiovascular system to date have focused on regional expression of specific genes. Here we also use RNA sequencing results from the sheep heart and cardiac valves to further explore the transcriptome of the cardiovascular system in this large animal. Our results demonstrate that there is a balance between genes that promote and those that suppress mineralisation during development and across cardiovascular tissues. We show extensive expression of genes encoding proteins involved in formation and maintenance of the extracellular matrix in cardiovascular tissues, and high expression of haematopoietic genes in the cardiac valves. Our analysis will support future research into the functions of implicated genes in the development of vascular calcification, and increase the utility of the sheep as a large animal model for understanding cardiovascular disease. This study provides a foundation to explore the transcriptome of the developing cardiovascular system and is a valuable resource for the fields of mammalian genomics and cardiovascular research.