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Role of Scl39a13/ZIP13 in cardiovascular homeostasis
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- Lufang Zhou
- editor
Description
<jats:p>Zinc plays a critical role in many physiological processes, and disruption of zinc homeostasis induces various disorders, such as growth retardation, osteopenia, immune deficiency, and inflammation. However, how the imbalance in zinc homeostasis leads to heart disease is not yet fully understood. Cardiovascular diseases are a major cause of death worldwide, and the development of novel therapeutic targets to treat it is urgently needed. We report that a zinc transporter, ZIP13, regulates cardiovascular homeostasis. We found that the expression level of <jats:italic>Zip13</jats:italic> mRNA was diminished in both primary neonatal cardiomyocytes and mouse heart tissues treated with the cardiotoxic agent doxycycline. Primary neonatal cardiomyocytes from <jats:italic>Zip13</jats:italic> gene-knockout (KO) mice exhibited abnormal irregular arrhythmic beating. RNA-seq analysis identified 606 differentially expressed genes in <jats:italic>Zip13</jats:italic>-KO mouse-derived primary neonatal cardiomyocytes and Gene ontology (GO) analysis revealed that both inflammation- and cell adhesion-related genes were significantly enriched. In addition, telemetry echocardiography analysis suggested that arrhythmias were likely to occur in <jats:italic>Zip13</jats:italic>-KO mice, in which elevated levels of the cardiac fibrosis marker <jats:italic>Col1a1</jats:italic>, vascular inflammation-related gene <jats:italic>eNOS</jats:italic>, and Golgi-related molecule <jats:italic>GM130</jats:italic> were observed. These results indicate the physiological importance of ZIP13—it maintains cardiovascular homeostasis by resolving inflammation and stress response. Our findings suggest that optimizing ZIP13 expression and/or function may improve cardiovascular disease management.</jats:p>
Journal
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- PLOS ONE
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PLOS ONE 17 (10), e0276452-, 2022-10-21
Public Library of Science (PLoS)
