scholarly journals Cathelicidin Modulates Vascular Smooth Muscle Cell Phenotypic Switching through ROS/IL-6 Pathway

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 491
Author(s):  
Xiaoliang Dong ◽  
Di Wu ◽  
Yihan Zhang ◽  
Lingling Jia ◽  
Xiaohua Pan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Nuclear Factor Κb ◽  
Janus Kinase ◽  
Phenotypic Switching ◽  
Phenotypic Transformation ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Relationship Of

Vascular smooth muscle cells (VSMC) are stromal cells of the blood vessels and their differentiation is thought to be essential during atherosclerosis. Cathelicidin-related antimicrobial peptides (CRAMP) are suggested to play a role in the development of atherosclerosis. Even so, the relationship of CRAMP and VSMC remains unclear. The present study was to determine whether CRAMP regulates VSMC phenotypic transformation and underlying mechanisms. We demonstrated that CRAMP could reverse platelet-derived growth factor-BB (PDGF-BB)-induced VSMC phenotypic transformation, evidencing by increasing α-smooth muscle actin (α-SMA), smooth muscle 22α (SM22α) and decreasing of proliferation and migration. Further studies showed that CRAMP inhibited nuclear factor κB (NF-κB)-induced autocrine of interleukin-6 (IL-6), which further activated of janus kinase 2 (JAK2)/signal transducer and activator 3 (STAT3). Meanwhile, our data showed that CRAMP can significantly inhibit PDGF-BB enhanced intracellular reactive oxygen species (ROS) level which further affected the NF-κB signaling pathway, indicating that CRAMP can regulate the phenotypic transformation of VSMC by regulating oxidative stress. These results indicated that CRAMP regulated the differentiation of VSMC by inhibiting ROS-mediated IL-6 autocrine, suggesting that targeting CRAMP is a potential avenue for regulating the differentiation of VSMC and treatment of atherosclerosis.

scholarly journals MicroRNA-145 Involves in the Pathogenesis of Renal Vascular Lesions and May Become a Potential Therapeutic Target in Patients with Juvenile Lupus Nephritis

2019 ◽  
Vol 44 (4) ◽  
pp. 643-655 ◽  
Author(s):  
Zhaomin Cai ◽  
Wei Xiang ◽  
Xiaojie Peng ◽  
Yan Ding ◽  
Wang Liao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Lupus Nephritis ◽  
Smooth Muscle Actin ◽  
Vascular Lesions ◽  
Alpha Smooth Muscle Actin ◽  
Migration Ability ◽  
Phenotypic Transformation ◽  
And Migration ◽  
Renal Vascular ◽  
Proliferation And Migration

Aims: The current study was conducted with the central objective of investigating the expression of microRNA-145 (miR-145) in renal vascular lesions (RVLs) in juvenile lupus nephritis (JLN) and its possible mechanism. Methods: The clinical data of 49 JLN patients confirmed by renal biopsy were collected and followed by grouping according to the RVLs score after hematoxylin-eosin staining: mild, moderate, and severe groups. In situ hybridization was used to detect the expression of miR-145 in renal vessels which was then being compared among different RVLs groups. Up-LV-miR-145 and LV-miR-NC lentiviral vectors were constructed and transfected into human vascular smooth muscle cells (HVSMCs), respectively. After HVSMCs were treated with 10.0 µg/L platelet-derived growth factor (PDGF)-BB for 24 h, the proliferation, migration, and apoptosis of endothelial cells were detected by MTT, Transwell assay, and flow cytometry, respectively. Western blot was used to detect expression of alpha-smooth muscle actin (α-SM-actin) and osteopontin (OPN). Results: The expression of miR-145 in renal vascular cells was statistically significant. The higher the inner membrane ratio, the lesser the miR-145 expression. After treatment with PDGF-BB, expression of miR-145 in HVSMCs decreased, proliferation and migration ability enhanced, apoptosis decreased, α-SM-actin decreased, and OPN increased. The proliferation and migration ability of HVSMCs in the LV-miR-145 group suppressed, apoptosis enhanced, α-SM-actin increased, and OPN decreased. Conclusions: Our study revealed that miR-145 expression decreased with the increase of vascular damage. miR-145 can inhibit proliferation, migration, and differentiation phenotypic transformation of HVSMCs induced by PDGF-BB. miR-145 may be involved in the pathogenesis of RVLs and may be a new target for treatment of RVLs in lupus nephritis.

scholarly journals LncRNA MRAK048635_P1 is critical for vascular smooth muscle cell function and phenotypic switching in essential hypertension

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Genqiang Fang ◽  
Jia Qi ◽  
Liya Huang ◽  
Xianxian Zhao
Keyword(s):  
Smooth Muscle ◽  
Essential Hypertension ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Remodeling ◽  
Cell Function ◽  
Phenotypic Switching ◽  
And Migration ◽  
Proliferation And Migration

AbstractVascular remodeling caused by essential hypertension is a leading cause of death in patients, and vascular smooth muscle cell (VSMC) dysfunction and phenotypic switching result in vascular remodeling. Therefore, inhibiting cell dysfunction and phenotypic switching in VSMCs may be a new treatment strategy for essential hypertension. The aim of the current study is to explore the roles of long non-coding RNA (lncRNA) MRAK048635_P1 in VSMC function and phenotypic switching. The MRAK048635_P1 level was determined in spontaneously hypertensive rats (SHRs) and VSMCs isolated from SHRs. MRAK048635_P1 was knocked down using a specific siRNA in VSMCs isolated from the thoracic aorta of SHRs and Wistar–Kyoto rats. Then, the proliferation and migration of VSMCs were determined using a cell counting kit-8 (CCK-8), a 3H labeling method, a transwell assay, and a wound healing assay. Flow cytometry was used to test the effect of MRAK048635_P1 on VSMC apoptosis. The protein and mRNA levels of associated genes were measured through Western blotting, immunofluorescence, and Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). MRAK048635_P1 showed low expression during hypertension in vivo and in vitro. Down-regulation of lncRNA MRAK048635_P1 promoted proliferation and migration and inhibited apoptosis in VSMCs isolated from healthy rat vascular tissue and SHR-derived VSMCs. Importantly, we also found that down-regulation of MRAK048635_P1 could induce VSMC phenotypic switching from a contractile to a secretory phenotype. In conclusion, our findings reveal that decreased MRAK048635_P1 is probably an important factor for vascular remodeling by affecting VSMC cell function and phenotypic switching in essential hypertension.

S-(–)-equol alleviates stenosis of the injured carotid artery in Sprague Dawley rats by preventing the vascular smooth muscle cell phenotypic switch via inhibition of the MAPKp38-NFκBp65 signaling

2020 ◽  
Vol 10 (8) ◽  
pp. 1237-1248
Author(s):  
Hongchen Wu ◽  
Piming Nie ◽  
Zhenghua Zhou ◽  
Jun Hu ◽  
Guangjian Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Carotid Artery ◽  
Vascular Smooth Muscle ◽  
Carotid Stenosis ◽  
Phenotypic Switching ◽  
Sprague Dawley ◽  
Phenotypic Switch ◽  
Sd Rats ◽  
And Migration ◽  
Proliferation And Migration

Phenotypic switching of the vascular smooth muscle cells (VSMCs) is closely related to an in-stent restenosis (ISR). This study aimed to investigate whether S-(–)-equol prevented the phenotypic switch of the VSMCs as a potential treatment of an ISR. The carotid arteries of female Sprague Dawley (SD) rats with or without a carotid injury and ovariectomy were harvested after 4 weeks of treatment with S-(–)-equol. Stenosis of the carotid artery and two phenotype-related proteins-α smooth muscle actin (αSMA) and osteopontin (OPN)-were determined. The proliferation and migration capacities of VSMCs were determined by the CCK-8 and transwell assays, respectively. The expressions of αSMA, OPN, MAPKp38, p-MAPKp38, NF-κBp65, and p-NF-κBp65 were detected by a western blot. S-(–)-equol alleviated carotid stenosis and prevented the VSMC phenotypic switch in female SD rats with a carotid artery injury and a bilateral ovariectomy. S-(–)-equol inhibited the phenotypic switch of VSMCs, which was induced by PDGF-BB, and enhanced the proliferation and migration of VSMCs. The effects of S-(–)-equol on VSMCs were confirmed to be related to the inactivation of the GPER-MAPKp38-NF-κBp65 signaling in vitro and in vivo. Our results indicate that S-(–)-equol affects carotid stenosis by preventing the phenotypic switch of VSMCs via the GPER-MAPKp38-NF-κBp65 signaling pathway.

scholarly journals PDGFR-β modulates vascular smooth muscle cell phenotype via IRF-9/SIRT-1/NF-κB pathway in subarachnoid hemorrhage rats

2018 ◽  
Vol 39 (7) ◽  
pp. 1369-1380 ◽  
Author(s):  
Weifeng Wan ◽  
Yan Ding ◽  
Zongyi Xie ◽  
Qian Li ◽  
Feng Yan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Neurological Dysfunction ◽  
Cell Phenotype ◽  
Sprague Dawley ◽  
Contractile Phenotype ◽  
Phenotypic Transformation ◽  
Sirt1 Activator

Platelet-derived growth factor receptor-β (PDGFR-β) has been reported to promote phenotypic transformation of vascular smooth muscle cells (VSMCs). The purpose of this study was to investigate the role of the PDGFR-β/IRF9/SIRT-1/NF-κB pathway in VSMC phenotypic transformation after subarachnoid hemorrhage (SAH). SAH was induced using the endovascular perforation model in Sprague-Dawley rats. PDGFR-β small interfering RNA (siRNA) and IRF9 siRNA were injected intracerebroventricularly 48 h before SAH. SIRT1 activator (resveratrol) and inhibitor (EX527) were administered intraperitoneally 1 h after SAH induction. Twenty-four hours after SAH, the VSMC contractile phenotype marker α-smooth muscle actin (α-SMA) decreased, whereas the VSMC synthetic phenotype marker embryonic smooth muscle myosin heavy chain (Smemb) increased. Both PDGFR-β siRNA and IRF9 siRNA attenuated the induction of nuclear factor-κB (NF-κB) and enhanced the expression of α-SMA. The SIRT1 activator (resveratrol) preserved VSMC contractile phenotype, significantly alleviated neurological dysfunction, and reduced brain edema. However, these beneficial effects of PDGFR-β siRNA, IRF9 siRNA and resveratrol were abolished by the SIRT1 inhibitor (EX527). This study shows that PDGFR-β/IRF9/SIRT-1/NF-κB signaling played a role in the VSMC phenotypic transformation after SAH. Inhibition of this signaling cascade preserved the contractile phenotype of VSMCs, thereby improving neurological outcomes following SAH.

scholarly journals Activation of M3AChR (Type 3 Muscarinic Acetylcholine Receptor) and Nrf2 (Nuclear Factor Erythroid 2–Related Factor 2) Signaling by Choline Alleviates Vascular Smooth Muscle Cell Phenotypic Switching and Vascular Remodeling

2020 ◽  
Vol 40 (11) ◽  
pp. 2649-2664
Author(s):  
Xi He ◽  
Juan Deng ◽  
Xiao-Jiang Yu ◽  
Si Yang ◽  
Yang Yang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular Remodeling ◽  
Phenotypic Switching ◽  
Related Factor ◽  
Nuclear Factor ◽  
Ang Ii ◽  
Nrf2 Pathway ◽  
Phenotypic Transformation ◽  
Type 3

Objective: Phenotypic switching of vascular smooth muscle cells (VSMCs) plays a critical role in atherosclerosis, vascular restenosis, and hypertension. Choline exerts cardioprotective effects; however, little is known about its effects on VSMC phenotypic switching and vascular remodeling. Here, we investigated whether choline modulates VSMC phenotypic changes and explored the underlying mechanisms. Approach and Results: In cultured VSMCs, choline promoted Nrf2 (nuclear factor erythroid 2–related factor 2) nuclear translocation, inducing the expression of HO-1 (heme oxygenase-1) and NQO-1 (NAD[P]H quinone oxidoreductase-1). Consequently, choline ameliorated Ang II (angiotensin II)–induced increases in NOX (NAD[P]H oxidase) expression and the mitochondrial reactive oxygen species level, thereby attenuating Ang II–induced VSMC phenotypic switching, proliferation, and migration, presumably via M3AChRs (type 3 muscarinic acetylcholine receptors). Downregulation of M3AChR or Nrf2 diminished choline-mediated upregulation of Nrf2, HO-1, and NQO-1 expression, as well as inhibition of VSMC phenotypic transformation, suggesting that M3AChR and Nrf2 activation are responsible for the protective effects of choline. Moreover, activation of the Nrf2 pathway by sulforaphane suppressed Ang II–induced VSMC phenotypic switching and proliferation, indicating that Nrf2 is a key regulator of VSMC phenotypic switching and vascular homeostasis. In a rat model of abdominal aortic constriction in vivo, choline attenuated VSMC phenotypic transformation and vascular remodeling in a manner related to activation of the Nrf2 pathway. Conclusions: These results reveal that choline impedes VSMC phenotypic switching, proliferation, migration, and vascular remodeling by activating M3AChR and Nrf2-antioxidant signaling and suggest a novel role for Nrf2 in VSMC phenotypic modulation.

scholarly journals Metformin attenuates carotid neointimal hyperplasia by modulating the vascular smooth muscle cell phenotype transformation through upregulation of TET2, Nur77 and calponin

2021 ◽  
Vol 73 (1) ◽  
pp. 135-144
Author(s):  
Hao Lin ◽  
Shuo Cheng ◽  
Zhichao Yuan ◽  
Zhiqiang Yan ◽  
Jifa Zhang
Keyword(s):  
Smooth Muscle ◽  
Carotid Artery ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Neointimal Hyperplasia ◽  
Nuclear Antigen ◽  
Cell Phenotype ◽  
Alpha Smooth Muscle Actin ◽  
And Migration ◽  
Proliferation And Migration

Metformin is a drug used to treat type 2 diabetes based on its effectiveness as well as cardiovascular safety. Metformin has been shown to modulate proliferation and migration of vascular smooth muscle cells (VSMCs), but the underlying mechanisms of the effect of metformin on VSMC function remains unclear. We found that metformin inhibits VSMC proliferation and migration and upregulates the expression of nuclear receptor subfamily 4 group A member 1 (Nur77), ten-eleven translocation 2 (TET2), and calponin in vitro. In the carotid artery balloon injury model of rats, metformin effectively prevented neointimal hyperplasia in the carotid artery, including neointimal thickness, increased neointimal area, and the neointimal area/medial area ratio. It also reduced the number of proliferating cell nuclear antigen (PCNA)+ cells and increased the expression of Nur77, calponin and alpha-smooth muscle actin (?-SMA). These results show that metformin attenuates neointimal hyperplasia in balloon-injured carotid arteries via increased expression of TET2, Nur77 and calponin, and reduced expression of matrix metallopeptidase 9 (MMP-9).

scholarly journals TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential‐dependent coupling with PTEN

2019 ◽  
Vol 33 (9) ◽  
pp. 9785-9796 ◽  
Author(s):  
Takuro Numaga‐Tomita ◽  
Tsukasa Shimauchi ◽  
Sayaka Oda ◽  
Tomohiro Tanaka ◽  
Kazuhiro Nishiyama ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Plasma Membrane ◽  
Membrane Potential ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Phenotypic Switching ◽  
Plasma Membrane Potential
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