Abstract
The aim of this study is to explore the function of p21-activated kinase 4 (PAK4) in intimal hyperplasia (IH) and vascular smooth muscle cells (VSMCs) proliferation. We choose vascular samples from patients undergoing angioplasty in superficial femoral artery (SFA) as the experimental group and vascular samples from donors without clinical SFA restenosis as the control group, respectively. We draw from the results that both levels of mRNA and protein of PAK4 in the experimental group increased dramatically compared with the control group. IH arose from angioplasty of SFA. Moreover, overexpression of PAK4 dramatically contributed to cell proliferation of VSMCs and promoted cell cycle progression from G0/G1 phase (71.12 ± 0.69% versus 58.77 ± 0.77%, P < 0.001) into S phase (23.99 ± 0.21% versus 31.35 ± 0.33%, P < 0.001). Besides, PAK4 downregulated the level of p21 and enhanced the activity of Akt as well. And we conclude that PAK4 acts as a regulator of cell cycle progression of VSMC by mediating Akt signaling and controlling p21 levels, which further modulate IH and VSMCs' proliferation.
Highlights
Advanced angioplasty and stenting technology are two main therapeutic methods for treating cardiovascular disease
To define the clinical functional role of p21-activated kinase 4 (PAK4), we detected the mRNA and protein expression levels of PAK4 in tissues with intimal hyperplasia (IH) that arose from angioplasty. qRTPCR indicated that, compared with the control samples, IH significantly increased the mRNA level of PAK4 (Figure 1(b))
These results demonstrated that PAK4 may play a vital role in the pathogenesis of IH originated from angioplasty
Summary
Advanced angioplasty and stenting technology are two main therapeutic methods for treating cardiovascular disease. The p21-activated kinases (PAKs) are a family of serine/threonine kinases that are major effector proteins for the Rho GTPases Cdc and Rac, which are important for cell morphology and cytoskeletal reorganization [7, 8], as well as various cell processes including proliferation, migration, and survival [9,10,11]. PAK4 is expressed at low levels in the majority of normal adult tissues and accumulating documents have reported that the aberrant expression of PAK4 is closely related to the diverse cancers, such as glioma, breast cancer, colon and gastric cancers, and prostate cancer [12,13,14]. It has been reported that PAK4 plays an important role in the cell cycle through regulating the level of p21, a key member of the cyclin-dependent kinase- (CDK-) inhibitory protein family, in fibroblasts [16]. Till date, there is no documented evidence of its pathological significance in VSMCs proliferation
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