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Rationale :SM22 (or transgelin), an actin-binding protein abundant in vascular smooth muscle cells (VSMCs), is downregulated in atherosclerosis, aneurysm and various cancers. Abolishing SM22 in apolipoprotein E knockout mice accelerates atherogenesis. However, it is unclear whether SM22 disruption independently promotes arterial inflammation.Objective :To investigate whether SM22 disruption directly promotes inflammation on arterial injury and to characterize the underlying mechanisms.Methods and Results :Using carotid denudation as an artery injury model, we showed thatSm22 knockout (Sm22 −/− ) mice developed enhanced inflammatory responses with higher induction of proinflammatory genes, includingVcam1 ,Icam1 ,Cx3cl1 ,Ccl2 , andPtgs2 . Higher expression of these genes was confirmed in primarySm22 −/− VSMCs and in PAC1 cells afterSm22 knockdown, whereas SM22 recapitulation in primarySm22 −/− VSMCs decreased their expression. NFKB2 was prominently activated in both injured carotids ofSm22 −/− mice and in PAC1 cells afterSm22 knockdown and may mediate upregulation of these proinflammatory genes. As a NF-κB activator, reactive oxygen species (ROS) increased in primarySm22 −/− VSMCs and in PAC1 cells afterSm22 knockdown. ROS scavengers blocked NF-κB activation and induction of proinflammatory genes. Furthermore,Sm22 knockdown increasedSod2 expression and activated p47phox, reflecting contributions of mitochondria and NADPH oxidase to the augmented ROS production; this may result from actin and microtubule cytoskeletal remodeling.Conclusions :Our findings show that SM22 downregulation can induce proinflammatory VSMCs through activation of ROS-mediated NF-κB pathways. This study provides initial evidence linking VSMC cytoskeleton remodeling with arterial inflammation.

Disruption of SM22 Promotes Inflammation After Artery Injury via Nuclear Factor κB Activation