scholarly journals Huotan Jiedu Tongluo Decoction Inhibits Balloon-Injury-Induced Carotid Artery Intimal Hyperplasia in the Rat through the PERK-eIF2α-ATF4 Pathway and Autophagy Mediation

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Tenghui Tian ◽  
Keying Yu ◽  
Miao Zhang ◽  
Xiao Shao ◽  
Liping Chang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Carotid Artery ◽  
Smooth Muscle Cells ◽  
Intimal Hyperplasia ◽  
Muscle Cells ◽  
Nuclear Antigen ◽  
Signal Molecules ◽  
Pathological Feature ◽  
Balloon Injury ◽  
Related Factors

In-stent restenosis (ISR) is the main factor affecting the outcome of percutaneous coronary intervention (PCI), and its main pathological feature is neointimal hyperplasia. Huotan Jiedu Tongluo decoction (HTJDTLD) is an effective traditional Chinese medicine (TCM) prescription for the treatment of vascular stenosis diseases. However, the precise anti-ISR mechanism of HTJDTLD remains unclear. Here, we investigated whether HTJDTLD can inhibit the excessive activation of endoplasmic reticulum stress (ERS) and reduce the level of autophagy factors through regulating the PERK-eIF2α-ATF4 pathway, thereby inhibiting the proliferation of the intima of blood vessels damaged by balloon injury (BI) and preventing the occurrence of ISR. In this study, a 2F Fogarty balloon was used to establish a common carotid artery (CCA) BI model in male Sprague-Dawley rats. Then, HTJDTLD (16.33 g/kg/d) or atorvastatin (1.19 mg/kg/d) was administered by gavage. Four weeks later, hematoxylin-eosin (HE) and Masson staining of the injured CCA were performed to observe the histological changes in the CCA. Immunohistochemistry (IHC) was used to assess the proliferation and dedifferentiation of vascular smooth muscle cells (VSMCs) in the CCA. Western blotting and RT-PCR were used to measure the expression of ERS- and autophagy-related proteins and mRNAs in the CCA. The results indicated that HTJDTLD significantly alleviated BI-induced carotid artery intimal hyperplasia and fibrosis and reduced the neointimal area (NIA) and NIA/medial area (MA) ratio. In addition, HTJDTLD inhibited the proliferation and dedifferentiation of VSMCs, reduced the expression of proliferating cell nuclear antigen (PCNA), and increased the smooth-muscle-α-actin- (SMα-actin-) positive area. HTJDTLD also significantly reduced the expression of the ERS-related factors: GRP78, p-PERK/PERK, p-eIF2α/eIF2α, ATF4, and CHOP. In addition, the expression of the autophagy-related factors, Beclin1, LC3B, and ATG12, was significantly decreased. In addition, in vitro experiments showed that HTJDTLD inhibited the above-mentioned ERS signal molecules in human umbilical vein endothelial cells (HUVEC) and rat aortic smooth muscle cells (A7R5) induced by tunicamycin (TM) and played a crucial role in protecting cells from damage. HTJDTLD may be a very promising drug for the treatment of ISR.

Function and role of voltage-gated sodium channel NaV1.7 expressed in aortic smooth muscle cells

2009 ◽  
Vol 296 (1) ◽  
pp. H211-H219 ◽  
Author(s):  
Kentaro Meguro ◽  
Haruko Iida ◽  
Haruhito Takano ◽  
Toshihiro Morita ◽  
Masataka Sata ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
Intimal Hyperplasia ◽  
Muscle Cells ◽  
Rt Pcr ◽  
Balloon Injury ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Voltage Gated

Voltage-gated Na+ channel currents ( INa) are expressed in several types of smooth muscle cells. The purpose of this study was to evaluate the expression of INa, its functional role, pathophysiology in cultured human (hASMCs) and rabbit aortic smooth muscle cells (rASMCs), and its association with vascular intimal hyperplasia. In whole cell voltage clamp, INa was observed at potential positive to −40 mV, was blocked by tetrodotoxin (TTX), and replacing extracellular Na+ with N-methyl-d-glucamine in cultured hASMCs. In contrast to native aorta, cultured hASMCs strongly expressed SCN9A encoding NaV1.7, as determined by quantitative RT-PCR. INa was abolished by the treatment with SCN9A small-interfering (si)RNA ( P < 0.01). TTX and SCN9A siRNA significantly inhibited cell migration ( P < 0.01, respectively) and horseradish peroxidase uptake ( P < 0.01, respectively). TTX also significantly reduced the secretion of matrix metalloproteinase-2 6 and 12 h after the treatment ( P < 0.01 and P < 0.05, respectively). However, neither TTX nor siRNA had any effect on cell proliferation. L-type Ca2+ channel current was recorded, and INa was not observed in freshly isolated rASMCs, whereas TTX-sensitive INa was recorded in cultured rASMCs. Quantitative RT-PCR and immunostaining for NaV1.7 revealed the prominent expression of SCN9A in cultured rASMCs and aorta 48 h after balloon injury but not in native aorta. In conclusion, these studies show that INa is expressed in cultured and diseased conditions but not in normal aorta. The NaV1.7 plays an important role in cell migration, endocytosis, and secretion. NaV1.7 is also expressed in aorta after balloon injury, suggesting a potential role for NaV1.7 in the progression of intimal hyperplasia.

scholarly journals Increased telocytes involved in the proliferation of vascular smooth muscle cells in rat carotid artery balloon injury

2016 ◽  
Vol 59 (7) ◽  
pp. 678-685 ◽  
Author(s):  
Yanyan Li ◽  
Xiuxiu Zhang ◽  
Juan Gao ◽  
Han Xiao ◽  
Ming Xu
Keyword(s):  
Smooth Muscle ◽  
Carotid Artery ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Balloon Injury

Janus Kinase 3 Deficiency Promotes Vascular Reendothelialization

2021 ◽  
Author(s):  
Yung-Chun Wang ◽  
Dunpeng Cai ◽  
Xiao-Bing Cui ◽  
Ya-Hui Chuang ◽  
William P. Fay ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Injury ◽  
Intimal Hyperplasia ◽  
Carotid Arteries ◽  
Muscle Cells ◽  
Janus Kinase ◽  
Balloon Injury ◽  
Janus Kinase 3

Objective: The objective of this study is to determine the role of JAK3 (Janus kinase 3) in reendothelialization after vascular injury. Methods and Results: By using mouse carotid artery wire injury and rat balloon injury model, we found that JAK3 regulates reendothelialization and endothelial cell proliferation after vascular injury. JAK3 and phospho-JAK3 levels were increased in neointimal smooth muscle cells in response to vascular injury in mice. JAK3 deficiency dramatically attenuated the injury-induced intimal hyperplasia in carotid arteries of both male and female mice. Importantly, JAK3 deficiency caused an increased rate of reendothelialization following mechanical injury. Likewise, knockdown of JAK3 in medial smooth muscle cells elicited an accelerated reendothelialization with reduced intimal hyperplasia following balloon injury in rat carotid arteries. Interestingly, knockdown of JAK3 restored the expression of smooth muscle cell contractile protein smooth muscle α-actin in injury-induced intimal smooth muscle cells while increased the proliferating endothelial cells in the intima area. Conclusions: Our results demonstrate a novel role of JAK3 in the regeneration of endothelium after vascular injury, which may provide a new strategy to enhance reendothelialization while suppressing neointimal formation for effective vascular repair from injury.

Induction of Renin in Medial Smooth Muscle Cells by Balloon Injury

Hypertension ◽  
1997 ◽  
Vol 29 (4) ◽  
pp. 1044-1050 ◽  
Author(s):  
Naoharu Iwai ◽  
Masafumi Izumi ◽  
Tadashi Inagami ◽  
Masahiko Kinoshita
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Balloon Injury
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