Modulation of cysteine-rich protein 2 expression in vascular injury and atherosclerosis

Abstract

Vascular smooth muscle cells (VSMCs) of the arterial wall normally display a differentiated and contractile phenotype. In response to arterial injury, VSMCs switch to a synthetic phenotype, contributing to vascular remodeling. Cysteine-rich protein 2 (CRP2) is a cytoskeletal protein expressed in VSMCs and blunts VSMC migration in part by sequestering the scaffolding protein p130Cas at focal adhesions. CRP2 deficiency in mice increases neointima formation following arterial injury. The goal of this study was to use Csrp2 promoter-lacZ transgenic mice to analyze CRP2 expression during VSMC phenotypic modulation. In a neointima formation model after carotid artery cessation of blood flow, lacZ reporter activity and smooth muscle (SM) α-actin expression in the media were rapidly downregulated 4 days after carotid ligation. Fourteen days after ligation, there was a high level expression of both Csrp2 promoter activity and SM α-actin protein expression in neointimal cells. In atherosclerosis prone mice fed an atherogenic diet, Csrp2 promoter activity was detected within complex atherosclerotic lesions. Interestingly, Csrp2 promoter activity was also present in the fibrous caps of complicated atherosclerotic lesions, indicating that CRP2 might contribute to plaque stability. These findings support the concept that CRP2 contributes to the phenotypic modulation of VSMCs during vascular disease. Modulating transcription to increase CRP2 expression during vascular injury might attenuate vascular remodeling. In addition, increased CRP2 expression at the fibrous caps of advanced lesions might also serve to protect atherosclerotic plaques from rupture.

Identification of Mature Atherosclerotic Plaque Proteome Signatures Using Data-Independent Acquisition Mass Spectrometry

“…Other proteins with increased abundance linked to atherosclerosis were the cysteine and glycine-rich protein 2 (CSRP2), which modulates SMC phenotype and thus influences vascular remodeling and may thereby contribute to plaque stability, or the insulin-like growth factor binding protein 7 (IGFBP7), a cell-cycle arrest marker, which has been linked to ischemic conditions …”

Gene expression profiling in the hippocampus of adolescent rats after chronic alcohol administration

“…In this research, chronic alcohol treatment led to up‐regulation of Csrp2 , which encodes cysteine‐rich protein 2 (CRP2). Recently, some studies have demonstrated that CRP2 protein, which is responsible for cytoskeleton formation, is widely expressed in vascular smooth muscle cells (VSMCs) and Csrp2 − / − VSMCs exhibited enhancement of cell migration as well as an increase in neointima formation . Another study reported that after vascular injuries that provoke cell proliferation, the expression of CRP2 is decreased in arterial smooth muscle cells of rats .…”

“…Recently, some studies have demonstrated that CRP2 protein, which is responsible for cytoskeleton formation, is widely expressed in vascular smooth muscle cells (VSMCs) and Csrp2 −/− VSMCs exhibited enhancement of cell migration as well as an increase in neointima formation. 48,49 Another study reported that after vascular injuries that provoke cell proliferation, the expression of CRP2 is decreased in arterial smooth muscle cells of rats. 50 These reports imply that the CRP2 protein negatively affects proliferation of VSMCs and their migration into the intima after arterial injury.…”

Role of Acid-sensing Ion Channels (ASICs) in the Vascular Endothelial Cells Injury of Henoch- Schonlein Purpura Children

“…Destrin is responsible for the rapid rearrangement of actin structures in the cells [19], and has been shown to play a crucial role in cell motility [20]. α-skeletal muscle (SM-α) actin is a kind of [21]. Studies reported that the expression of SM-α decreased significantly in VSMCs due to some damage factors caused VSMCs damage [22].…”