Differential expression of endothelial derived galectins in response to shear stress

BACKGROUND: Endothelial cells function as mechanosensors, dynamically altering their functional response based on varying shear stress/flow patterns to maintain vascular homeostasis. Disturbed flow leads to endothelium dysfunction, promoting conditions such as atherosclerosis. Understanding the molecular impact of flow is crucial for the development of new therapeutic targets for vascular diseases. Galectins have been implicated in vascular diseases, specifically their role in inflammation. However, the regulation of endothelial galectins by shear stress remains unexplored.

METHODS: Galectin gene and protein expression were analysed from publicly available datasets or in human umbilical endothelial cells (HUVEC) and human arterial endothelial cells (HAEC) cultured under either shear stress induced by orbital shaking or static conditions by qPCR, immunofluorescence imaging and ELISA.

RESULTS: Laminar shear stress upregulated LGALS9 and downregulated LGALS1, while disturbed flow reversed these effects. Complex shear environments significantly increased Gal-3 and Gal-9 expression at both gene and protein levels, with distinct variations in surface expression and secretion. In vivo single-cell RNA sequencing (scRNAseq) revealed reduced Lgals9 expression in endothelial cells exposed to disturbed flow in carotid artery ligation models compared to laminar flow.

SIGNIFICANCE: These findings highlight that endothelial galectin expression is shear-regulated, which has significant implications for understanding galectin biology and there potential as therapeutic targets in vascular diseases influenced by shear stress.