SCD1 deficiency alters the perivascular secretory function of adipocytes and induces phenotypic changes in vascular...

Perivascular adipose tissue (PVAT) maintains vascular homeostasis by secreting vasoactive factors that interact with vascular smooth muscle cells (VSMCs). VSMCs maintaining the structure and function of blood vessels through their contractile phenotype. Under pathological conditions, the secretory function of PVAT changes from homeostatic to harmful. For this reason, VSMCs may undergo a phenotypic shift toward a synthetic state that is characterized by increases in proliferation and migration. Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids. SCD1 deficiency exacerbates atherosclerosis and PVAT inflammation. The present study investigated the effect of adipocyte-conditioned medium (ACM) that was derived from SCD1 knockout (SCD1 KO) PVAT adipocytes on VSMCs. The treatment of A7r5 cells with SCD1 KO ACM decreased markers of contractility and increased markers of the synthetic phenotype. Increases in the phosphorylation and nuclear translocation of extracellular signal-regulated kinases 1/2 and higher levels of active caspase-3 in VSMCs that were exposed to SCD1 KO ACM indicate increases in proliferation, migration, and apoptosis. Cytoskeletal disorganization and a lower contractile response to angiotensin II further confirmed this phenotypic shift. Higher levels of adipokines and cytokines in SCD1 KO ACM, which may promote the synthetic phenotype in VSMCs, may contribute to these effects. Additionally, collagen content in thoracic and abdominal aortas was significantly higher in SCD1 KO mice compared with wildtype mice, indicating an increase in extracellular matrix deposition. These findings indicate that factors that are secreted by SCD1-deficient PVAT promote a phenotypic change in VSMCs and may contribute to vascular remodeling.