Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Influence of the LINC00961/SPAAR Locus Loss on Murine Development, Myocardial Dynamics, and Cardiac Response to Myocardial Infarction

Version 1 : Received: 2 October 2020 / Approved: 5 October 2020 / Online: 5 October 2020 (17:47:46 CEST)

How to cite: Spiroski, A.; Sanders, R.; Meloni, M.; McCracken, I.; Thomson, A.; Brittan, M.; Gray, G.; Baker, A.H. The Influence of the LINC00961/SPAAR Locus Loss on Murine Development, Myocardial Dynamics, and Cardiac Response to Myocardial Infarction. Preprints 2020, 2020100102 (doi: 10.20944/preprints202010.0102.v1). Spiroski, A.; Sanders, R.; Meloni, M.; McCracken, I.; Thomson, A.; Brittan, M.; Gray, G.; Baker, A.H. The Influence of the LINC00961/SPAAR Locus Loss on Murine Development, Myocardial Dynamics, and Cardiac Response to Myocardial Infarction. Preprints 2020, 2020100102 (doi: 10.20944/preprints202010.0102.v1).

Abstract

Long non-coding RNAs (lncRNAs) have structural and functional roles in development and disease. We have previously shown that the LINC00961/SPAAR locus regulates endothelial cell function, and that both the lncRNA and micropeptide counter-regulate angiogenesis. To assess human cardiac cell SPAAR expression we mined a publicly available scRNSeq dataset and confirmed LINC00961 locus expression and hypoxic response in a murine endothelial cell line. We investigated post-natal growth and development, basal cardiac function, the cardiac functional response and tissue-specific response to myocardial infarction. To investigate the contribution of the LINC00961/SPAAR locus to determination of longitudinal growth, cardiac function, and response to myocardial infarction, we used a novel CRISPR/Cas9 locus knockout mouse line. Data mining suggested that SPAAR is predominantly expressed in human cardiac endothelial cells and fibroblasts, while murine LINC00961 expression is hypoxia-responsive in mouse endothelial cells. LINC00961-/- mice displayed a sex-specific delay in longitudinal growth and development, smaller left ventricular systolic and diastolic areas and volumes, and greater risk area following myocardial infarction compared with wildtype littermates. These data suggest a role for the LINC00961/SPAAR locus in cardiac endothelial cell and fibroblast cell function and hypoxic-response, and in growth and development, and basal cardiovascular function in adulthood.

Subject Areas

lncRNA; LINC00961; SPAAR; scRNASeq; CRISPR/Cas9; cardiovascular physiology; fetal growth restriction; myocardial infarction

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