scholarly journals Aortic dissection is associated with reduced polycystin-1 expression, an abnormality that leads to increased ERK phosphorylation in vascular smooth muscle cells

2016 ◽  
Author(s):  
J. Feng ◽  
S. Ge ◽  
L. Zhang ◽  
H. Che ◽  
C. Liang
Keyword(s):  
Smooth Muscle ◽  
Aortic Dissection ◽  
Vascular Smooth Muscle ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
High Morbidity ◽  
Biological Processes ◽  
Phenotypic Switch ◽  
Erk Phosphorylation

The vascular smooth muscle cell (VSMC) phenotypic switch is a key pathophysiological change in various cardiovascular diseases, such as aortic dissection (AD), with a high morbidity. Polycystin-1 (PC1) is significantly downregulated in the VSMCs of AD patients. PC1 is an integral membrane glycoprotein and kinase that regulates different biological processes, including cell proliferation, apoptosis, and cell polarity. However, the role of PC1 in intracellular signaling pathways remains poorly understood. In this study, PC1 downregulation in VSMCs promoted the expression of SM22α, ACTA2 and calponin 1 (CNN1) proteins. Furthermore, PC1 downregulation in VSMCs upregulated phospho-MEK, phospho-ERK and myc, but did not change phospho-JNK and phospho-p38. These findings suggest that the MEK/ERK/myc signaling pathway is involved in PC1-mediated human VSMC phenotypic switch. Opposite results were observed when an ERK inhibitor was used in VSMCs downregulated by PC1. When the C-terminal domain of PC1 (PC1 C-tail) was overexpressed in VSMCs, the expression levels of phosphor-ERK, myc, SM22α, ACTA2 and CNN1 proteins were downregulated. The group with the overexpressed mutant protein (S4166A) in the PC1 C-tail showed similar results to the group with the downregulated PC1 in VSMCs. These results suggest that the Ser at the 4166 site in PC1 is crucial in the PC1 mediated MEK/ERK/myc signaling pathway, which might be the key pathophysiological cause of AD.

Potential role of insulin signaling on vascular smooth muscle cell migration, proliferation, and inflammation pathways

2012 ◽  
Vol 302 (4) ◽  
pp. C652-C657 ◽  
Author(s):  
Eugenio Cersosimo ◽  
Xiaojing Xu ◽  
Nicolas Musi
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Insulin Signaling ◽  
Primary Cultures ◽  
Muscle Cells ◽  
Mapk Signaling ◽  
Akt Phosphorylation ◽  
Erk Phosphorylation

To investigate the role of insulin signaling pathways in migration, proliferation, and inflammation of vascular smooth muscle cells (VSMCs), we examined the expression of active components of the phosphatidyl inositol 3 (PI-3) kinase (p-Akt) and mitogen-activated protein kinase (MAPK) (p-Erk) in primary cultures of VSMCs from human coronary arteries. VSMCs were treated in a dose-response manner with insulin (0, 1, 10, and 100 nM) for 20 min, and Akt and Erk phosphorylation were measured by Western blot analysis. In separate experiments, we evaluated the effect of 200 μM palmitate, in the presence and absence of 8 μM pioglitazone, on insulin-stimulated (100 nM for 20 min) Akt and Erk phosphorylation. The phosphorylation of Akt and Erk in VSMCs exhibited a dose dependency with a three- to fourfold increase, respectively, at the highest dose (100 nM). In the presence of palmitate, insulin-induced Akt phosphorylation was completely abolished, and there was a threefold increase in p-Erk. With addition of pioglitazone, the phosphorylation of Akt by insulin remained unchanged, whereas insulin-stimulated Erk phosphorylation was reduced by pioglitazone. These data in VSMCs indicate that high palmitate decreases insulin-stimulated Akt phosphorylation and stimulates MAPK, whereas preexposure peroxisome proliferator-activated receptor-γ agonist pioglitazone preserves Akt phosphorylation and simultaneously attenuates MAPK signaling. Our results suggest that metabolic and mitogenic insulin signals have different sensitivity, are independently regulated, and may play a role in arterial smooth muscle cells migration, proliferation, and inflammation in conditions of acute hyperinsulinemia.

scholarly journals Nitro-linoleic acid inhibits vascular smooth muscle cell proliferation via the Keap1/Nrf2 signaling pathway

2007 ◽  
Vol 293 (1) ◽  
pp. H770-H776 ◽  
Author(s):  
Luis Villacorta ◽  
Jifeng Zhang ◽  
Minerva T. Garcia-Barrio ◽  
Xi-lin Chen ◽  
Bruce A. Freeman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Linoleic Acid ◽  
Vascular Smooth Muscle ◽  
Signaling Pathway ◽  
Related Factor ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Vsmc Proliferation ◽  
Nrf2 Signaling Pathway

Nitroalkenes, the nitration products of unsaturated fatty acids formed via NO-dependent oxidative reactions, have been demonstrated to exert strong biological actions in endothelial cells and monocytes/macrophages; however, little is known about their effects on vascular smooth muscle cells (VSMCs). The present study examined the role of nitro-linoleic acid (LNO2) in the regulation of VSMC proliferation. We observed that LNO2 inhibited VSMC proliferation in a dose-dependent manner. In addition, LNO2 induced growth arrest of VSMCs in the G1/S phase of the cell cycle with an upregulation of the cyclin-dependent kinase inhibitor p27kip1. Furthermore, LNO2 triggered nuclear factor-erythroid 2-related factor 2 (Nrf2) nuclear translocation and activation of the antioxidant-responsive element-driven transcriptional activity via impairing Kelch-like ECH-associating protein 1 (Keap1)-mediated negative control of Nrf2 activity in VSMCs. LNO2 upregulated the expression of Nrf2 protein levels, but not mRNA levels, in VSMCs. A forced activation of Nrf2 led to an upregulation of p27kip1 and growth inhibition of VSMCs. In contrast, knock down of Nrf2 using an Nrf2 siRNA approach reversed the LNO2-induced upregulation of p27kip1 and inhibition of cellular proliferation in VSMCs. These studies provide the first evidence that nitroalkene LNO2 inhibits VSMC proliferation through activation of the Keap1/Nrf2 signaling pathway, suggesting an important role of nitroalkenes in vascular biology.

scholarly journals Ambient Particulate Matter Induces Vascular Smooth Muscle Cell Phenotypic Changes via NOX1/ROS/NF-κB Dependent and Independent Pathways: Protective Effects of Polyphenols

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 782
Author(s):  
Chia-Chi Ho ◽  
Yu-Cheng Chen ◽  
Ming-Hsien Tsai ◽  
Hui-Ti Tsai ◽  
Chen-Yi Weng ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Particulate Matter ◽  
Vascular Smooth Muscle ◽  
Signaling Pathway ◽  
Proinflammatory Cytokines ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Cytokine Secretion ◽  
Ambient Particulate Matter ◽  
Migration Ability ◽  
Cytokines Secretion

Epidemiological studies have demonstrated an association between ambient particulate matter (PM) exposure and vascular diseases. Here, we observed that treatment with ambient PM increased cell migration ability in vascular smooth muscle cells (VSMCs) and pulmonary arterial SMCs (PASMCs). These results suggest that VSMCs and PASMCs transitioned from a differentiated to a synthetic phenotype after PM exposure. Furthermore, treatment with PM increased intracellular reactive oxygen species (ROS), activated the NF-κB signaling pathway, and increased the expression of proinflammatory cytokines in VSMCs. Using specific inhibitors, we demonstrated that PM increased the migration ability of VSMCs via the nicotinamide–adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX1)/ROS-dependent NF-κB signaling pathway, which also partially involved in the induction of proinflammatory cytokines. Finally, we investigated whether nature polyphenolic compounds prevent PM-induced migration and proinflammatory cytokines secretion in VSMCs. Curcumin, resveratrol, and gallic acid prevented PM2.5-induced migration via the ROS-dependent NF-κB signaling pathway. However, honokiol did not prevent PM2.5-induced migration or activation of the ROS-dependent NF-κB signaling pathway. On the other hand, all polyphenols prevented PM2.5-induced cytokines secretion. These data indicated that polyphenols prevented PM-induced migration and cytokine secretion via blocking the ROS-dependent NF-κB signaling pathway in VSMCs. However, other mechanisms may also contribute to PM-induced cytokine secretion.

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