LRRC8A knoutdown reduces blood pressue by inhibiting MLCK/MYPT1/MLC signal pathway

This study employs RNA sequencing to comprehensively profile the transcriptome of the vascular smooth muscle cell (VSMC) layer from the abdominal aorta in 12-week-old LOXP (control) and VSMC-specific LRRC8A knockout (CKO) mice. Our primary objective was to investigate the molecular mechanisms underlying the hypotensive phenotype observed in CKO mice, focusing on the impact of LRRC8A deletion on the VSMC transcriptional landscape.Following ethical guidelines, aortas were freshly isolated and immediately processed. The abdominal aorta was meticulously cleaned of perivascular adipose and connective tissues. Using fine microdissection, the outer adventitial layer and the inner endothelial layer were carefully removed to isolate the pure medial layer, which is highly enriched in VSMCs. This precise isolation ensures the transcriptomic data primarily reflects VSMC biology with minimal contamination from other cell types.Total RNA was extracted from the medial layer using the TRIzol reagent method, ensuring high integrity and quality. RNA quality was verified by spectrophotometry and bioanalyzer. Sequencing libraries were prepared and subjected to high-throughput sequencing on the Illumina platform.Our transcriptomic analysis revealed significant alterations in pathways related to VSMC contraction in CKO mice. Notably, we identified a marked upregulation of CALCRL (Calcitonin Receptor-Like Receptor) and RAMP1 (Receptor Activity-Modifying Protein 1), which together form the functional receptor for the potent vasodilator CGRP (Calcitonin Gene-Related Peptide). The coordinated induction of these key receptor components is a central finding of our study and represents a likely mechanism contributing to the observed reduction in vascular tone and blood pressure in the CKO model. This dataset provides a foundational resource for understanding how the LRRC8A/VRAC pathway influences vascular smooth muscle function and systemic blood pressure.