Investigation of calcium regulatory processes and their role in a natural large animal model of altitude-associated pulmonary hypertension sensitivity leading to heart failure. Bos taurus breed:American Angus

The pathophysiological development and progression of PH are polygenic in nature. There is a knowledge gap that exists between the associated pathology and the genes involved in hypoxia-induced models of PH. Calcium is a key mediator of the cardiac and arterial physiology and function, impacting processes related to contractility and tissue morphology. Gene expression results from RNA-sequencing and genome-wide association data comparing cattle with high and low pulmonary arterial pressures identified genes with functional roles in calcium signaling, homeostasis, and utilization. Differentially expressed genes identified in preliminary studies include solute carrier family 8 member A1, troponin I, calcium/calmodulin-dependent protein kinase, and ATPase sarcoplasmic reticulum calcium transporting 1 in multiple functional pathways associated with cardiac and pulmonary vascular physiology. The current proposal seeks to address the hypothesis that intra- and extra-cellular calcium availability and usage plays a role in the development and susceptibility of an individual to PH. The identification of tissue-specific genes pre- or post-transcriptionally regulated by calcium will aid in the early recognition of cattle susceptible to pulmonary hypertension, as well as ontogeny-associated expression differences. The current data will address the hypothesis by characterizing and comparing the ontogeny of gene expression (RNA-seq) related to calcium signaling, homeostasis, utilization, and regulation for PH susceptibility in cattle.