VSMC DDR1 Mechanosensation Aggravates Atherosclerosis via Paracrine Signaling.

In a CKD-hyperlipidemia mouse model, SMC DDR1 mechanosensing links arterial stiffening to higher THBS1, worsening atherosclerotic burden.

• Why it matters: CKD raises cardiovascular risk, but how arterial stiffness translates into atherogenesis through SMC-to-endothelial communication is unclear.
• What they did: The study integrated single-cell RNA-seq, secretome proteomics, and bulk RNA-seq with stiffness-controlled matrix models and endothelial assays, then tested SMC-specific Ddr1 deletion and the DDR1 dephosphorylation-targeting chimera DEPTAC in vivo.
• The result: THBS1 was identified as a stiffness-induced SMC secretory effector; stiff matrices increased THBS1-driven endothelial proliferation, migration, and leukocyte adhesion, while THBS1 knockdown and SMC Ddr1 deletion or DEPTAC reduced THBS1, vascular stiffening, and atherosclerosis.

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