Ginkolide A-Gold Nanoparticles Inhibit Vascular Smooth Muscle Proliferation And Migration In Vitro And Reduces Intimal Hyperplasia In A Mouse Model

2011 ◽  
Vol 165 (2) ◽  
pp. 253-254
Author(s):  
S.M. Weakley ◽  
X. Wang ◽  
H. Mu ◽  
P.H. Lin ◽  
Q. Yao ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Smooth Muscle ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Intimal Hyperplasia ◽  
Smooth Muscle Proliferation ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals Salusin-α Inhibits Proliferation and Migration of Vascular Smooth Muscle Cell via Akt/mTOR Signaling

2018 ◽  
Vol 50 (5) ◽  
pp. 1740-1753 ◽  
Author(s):  
Shoucui Gao ◽  
Liran Xu ◽  
Yali Zhang ◽  
Qingqing Yu ◽  
Jiayan Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Atherosclerotic Lesion ◽  
Cell Counting ◽  
Matrix Metalloproteinase 2 ◽  
Aortic Lesion ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: The proliferation and migration of vascular smooth muscle cells (VSMCs) are key steps in the progression of atherosclerosis. The aim of the present study was to investigate the potential roles of salusin-α in the functions of VSMCs during the development of atherosclerosis. Methods: In vivo, the effects of salusin-α on atherogenesis were examined in rabbits fed a cholesterol diet. The aortas were en face stained with Sudan IV to evaluate the gross atherosclerotic lesion size. The cellular components of atherosclerotic plaques were analyzed by immunohistochemical methods. In vitro, Cell Counting Kit-8 and wound-healing assays were used to assess the effects of salusin-α on VSMC proliferation and migration. In addition, western blotting was used to evaluate the total and phosphorylated levels of Akt (also known as protein kinase B) and mammalian target of rapamycin (mTOR) in VSMCs. Results: Salusin-α infusion significantly reduced the aortic lesion areas of atherosclerosis, with a 39% reduction in the aortic arch, a 71% reduction in the thoracic aorta, and a 71% reduction in the abdominal aorta; plasma lipid levels were unaffected. Immunohistochemical staining showed that salusin-α decreased both macrophage- and VSMC-positively stained areas in atherosclerotic lesions by 54% and 69%, cell proliferative activity in the intima and media of arteriosclerotic lesions, and matrix metalloproteinase 2 (MMP-2) and MMP-9 expression in plaques. Studies using cultured VSMCs showed that salusin-α decreased VSMC migration and proliferation via reduced phosphorylation of Akt and mTOR. Conclusion: Our data indicate that salusin-α suppresses the development of atherosclerosis by inhibiting VSMC proliferation and migration through the Akt/mTOR pathway.

Abstract 311: TGFb/Smad3 Stimulation Drives Smooth Muscle Cell De-differentiation

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Daniel M DiRenzo ◽  
Xudong Shi ◽  
Stephen Seedial ◽  
Lian-wang Guo ◽  
Bo Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Balloon Angioplasty ◽  
Intimal Hyperplasia ◽  
Cellular Proliferation ◽  
Smooth Muscle Actin ◽  
Tgfβ Signaling ◽  
And Migration ◽  
Proliferation And Migration

Restenosis, or vessel re-narrowing, occurs in approximately 25-50% of arterial interventions involving balloon angioplasty due to the formation of a proliferative plaque in the vessel lumen termed neo-intimal hyperplasia. Arterial smooth muscle cells (SMCs) contribute to neo-intimal hyperplasia through a de-differentiation process that includes downregulation of their contractile gene expression and conversion to a phenotype that includes proliferation, migration, and matrix synthesis. Expression of TGFβ and its downstream signaling protein, Smad3, are greatly upregulated following vascular injury, including balloon angioplasty. Classically, TGFβ signaling has been shown to suppress SMC proliferation and migration in vitro, however, Smad3 overexpressing SMCs demonstrate enhanced proliferation and migration. Furthermore, overexpression of Smad3 in rat carotid arteries enhances neo-intimal hyperplasia following balloon angioplasty. These results lead us to hypothesize that TGFβ signaling, in the context of upregulated Smad3, drives SMC de-differentiation leading to enhanced cellular proliferation and migration. We utilized primary rat SMCs infected with adenovirus constructs overexpressing Smad3 or GFP control and performed gene expression microarrays 24 hours following TGFβ administration. We observed statistically significant (p<0.05) upregulation of 145 genes and downregulation of 76 genes by more than 3-fold. GO term analysis revealed that genes involved in embryonic tissue development (41 genes) and stem/progenitor cell differentiation (27 genes) were significantly enriched in TGFβ/Smad3 stimulated cells. Confirmatory qRT-PCR demonstrated that the contractile genes SM-MHC, smooth muscle actin, and calponin were significantly downregulated -6.3, -2.7 and -2.1 fold, respectively. In contrast, stem/developmental related genes Cxcr4, Cd34, Wnt11, Wnt2b and IL11 were significantly upregulated by 105.2, 22.3, 11.5, 14.0, and 12.5 fold, respectively. These results strongly suggest that TGFβ/Smad3 stimulation is a powerful de-differentiation signal in SMCs and plays an important role in the development of neo-intimal hyperplasia.

Sign in / Sign up

Export Citation Format

Share Document