scholarly journals SRPK1 gene silencing promotes vascular smooth muscle cell proliferation and vascular remodeling via inhibition of the PI3K/Akt signaling pathway in a rat model of intracranial aneurysms

2018 ◽  
Vol 25 (2) ◽  
pp. 233-244 ◽  
Author(s):  
Xin-Guo Li ◽  
Yi-Bao Wang
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Gene Silencing ◽  
Smooth Muscle Cell ◽  
Rat Model ◽  
Vascular Remodeling ◽  
Intracranial Aneurysms ◽  
Akt Signaling ◽  
Akt Signaling Pathway

Abstract 315: Krüppel-like Factor 5 Promotes Vascular Remodeling in a Biphasic Manner by Inhibiting Vascular Smooth Muscle Cell Apoptosis and Stimulating Cell Growth

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Daigo Sawaki ◽  
Toru Suzuki ◽  
Kenichi Aizawa ◽  
Takayoshi Matsumura ◽  
Nanae Kada ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Cell Growth ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Cyclin D1 ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Vascular Remodeling ◽  
Neointimal Formation

Introduction: Vascular remodeling is characterized by cell proliferation and/or apoptosis with further phenotypic change of vascular cells. Vascular smooth muscle cell (VSMC)s, in particular, play a major role in the proliferative process such as neointimal formation and restenosis after angioplasty. In deciphering the transcriptional regulatory mechanisms in cardiovascular remodeling, Krüppel-like factor 5 (KLF5) was originally isolated as a regulatory factor of phenotypically modulated VSMCs. Past studies collectively have shown that KLF5 can induce cell growth pathologically in non-cardiovascular cells. However, how KLF5 contributes to vascular remodeling, notably its effects on apoptosis in the vascular lesion, had yet to be addressed. In the present study, we have aimed to address the effects of KLF5 not only on VSMC growth but also on apoptosis in vascular remodeling. Methods&Results: We performed adenoviral overexpression of KLF5 and other related factors after rat carotid balloon injury. In the early phase (48 hours after injury), KLF5 administered animals showed significantly decreased TUNEL positive cells in the medial layer. In the chronic phase (14 days after injury), apoptotic cells were recognized neither in the KLF5 animals nor in the others. While, neointimal formation and PCNA labeling index significantly increased in the KLF5 animals. Rat VSMCs transfected with KLF5 showed marked increase in cell proliferation and BrdU uptake. Additionally, cleavage of caspase-3 recognized in the quiescent VSMCs was attenuated after transfection of KLF5. Even under apoptotic stimulation using anisomysin, KLF5 overexpression resulted in significant inhibition of apoptosis induction. Further, KLF5 up-regulated gene expression of cell cycle factors such as cyclin D1, and conversely, knockdown of KLF5 by RNA interference showed down-regulation of cyclin D1 and impairment of VSMC proliferation. Conclusion: These findings taken together suggest that KLF5 plays a central role in VSMC proliferative pathologies such as vascular remodeling through biphasic contribution; inhibition of apoptosis and growth stimulation. Therapeutic intervention targeted against KLF5 may be potentially exploitable for VSMC proliferative pathology.

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