Mechanical Strain Induced Expression of Matrix Metalloproteinase-9 via Stretch-Activated Channels in Rat Abdominal Aortic Dissection

Qiu, Zhihuang; Cao, Hua; Chen, Qiang; Peng, Hua

doi:10.12659/msm.899547

Cited by 10 publications

(6 citation statements)

References 25 publications

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“…Stretch-activated channel (SAC) was initially discovered in skeletal muscle cells by Guharay , [ 20 ] and subsequent studies have shown that SAC is widely present in various cell s[ 21 ]. Qiu found that mechanical tension stimulates the SAC signaling pathway and regulates the expression of corresponding mRNAs and proteins in a rat aortic dissection mode l[ 22 ]. The pathophysiological similarity between PH-LHD and aortic dissection is that the vasculature is stimulated by mechanical tension which causes vascular remodeling.…”

Section: Discussionmentioning

confidence: 99%

Mechanical stretching of the pulmonary vein mediates pulmonary hypertension due to left heart disease by regulating SAC/MAPK pathway and the expression of IL-6 and TNF-α

Huang

Liu

Pan

et al. 2021

J Cardiothorac Surg

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Background This study aimed to explore whether the mechanical stretching-induced expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in pulmonary veins occurred through the stretch-activated channel (SAC)/ mitogen-activated protein kinases (MAPKs) pathway. Methods Sixty male Sprague-Dawley rats were divided into three sham groups and seven model groups. A metal clip was placed on the ascending aorta in the model group to establish PH-LHD rat model. The sham group received a similar operation without ascending aorta clamped. On day 25, pulmonary vein was given mechanical stretching with 0 g, 2.0 g tension in two model groups and two sham groups. Another four model groups were given 2.0 g tension after MAPKs pathway inhibitors soaked. The last sham group and model group rats’ pulmonary veins, pulmonary artery and lung tissues were obtained on day 35. Pulmonary vein, pulmonary artery and lung tissue were evaluated by echocardiography, HE staining, immunohistochemistry and western blotting respectively. Results On day 25, left heart weight, right ventricular pressure (35.339 cmH2O) and left atrial pressure (13.657 cmH2O) were increased in model group than those in sham group. Echocardiography showed left heart failure in the PH-LHD group (Interventrieular septum dimension 1.716 mm, left ventricular internal end diastolic dimension 4.888 mm, left ventricular posterior wall thickness in diastole 1.749 mm, ejection fraction 76.917%). But there was no difference in lung tissue between the sham group and PH-LHD group as showed by HE staining. Our results showed that the expression of IL-6 and TNF-α was highly expressed in PH-LHD rats’ serum and pulmonary vein, which were further increased after 2.0 g tension was given and were decreased after SAC/MAPKs inhibitors treatment. Meanwhile, on day 25, immunohistochemistry analysis showed the expression of IL-6 and TNF-α was higher in the PH-LHD rats’ pulmonary vein than that in pulmonary artery and lung tissue, and these expressions in pulmonary vein of PH-LHD group were also higher than that in sham group. However, on day 35, IL-6 and TNF-α were all increased in the pulmonary veins, arteries and lung tissues. Besides, our results uncovered that SAC/MAPKs pathway were upregulating in PH-LHD rats’ pulmonary vein. Conclusion In conclusion, pulmonary vein mechanical stretching exacerbated PH-LHD possibly through the SAC/MAPKs pathway and upregulating expression of IL-6 and TNF-α.

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Section: Discussionmentioning

confidence: 99%

Mechanical stretching of the pulmonary vein mediates pulmonary hypertension due to left heart disease by regulating SAC/MAPK pathway and the expression of IL-6 and TNF-α

Huang

Liu

Pan

et al. 2021

J Cardiothorac Surg

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“…Studies also testified that mechanical stretching can activate the phosphorylation of the MAPK pathway [28,29]. Also, studies have shown that the expression of MMP-9 and TGF-β1 in tissues may be related to stretch-activated channel (SAC) and mitogen-activated protein kinase (MAPK) signaling pathway [12,30,31]. Therefore, we speculated that SAC and MAPK signaling pathway may be potential regulatory molecules in PH-LHD.…”

Section: Introductionmentioning

confidence: 88%

“…Recently, Qiu et al demonstrated that mechanical stretching could up-regulate the expression of MMP-9 in the smooth muscle cells from animals with aortic dissection through SAC/ NF-κB signaling pathway [30]. The mechanical stress of the vascular wall during aortic dissection may influence the structure and function of cells, tissues and organs [44].…”

Section: Plos Onementioning

confidence: 99%

Mechanical stretching of pulmonary vein stimulates matrix metalloproteinase-9 and transforming growth factor-β1 through stretch-activated channel/MAPK pathways in pulmonary hypertension due to left heart disease model rats

et al. 2020

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Pulmonary hypertension due to left heart disease (PH-LHD) is a momentous pulmonary hypertension disease, and left heart disease is the most familiar cause. Mechanical stretching may be a crucial cause of vascular remodeling. While, the underlining mechanism of mechanical stretching-induced in remodeling of pulmonary vein in the early stage of PH-LHD has not been completely elucidated. In our study, the PH-LHD model rats were successfully constructed. After 25 days, doppler echocardiography and hemodynamic examination were performed. In addition, after treatment, the levels of matrix metalloproteinase-9 (MMP-9) and transforming growth factor-β1 (TGF-β1) were determined by ELISA, immunohistochemistry and western blot assays in the pulmonary veins. Moreover, the pathological change of pulmonary tissues was evaluated by H&E staining. Our results uncovered that left ventricular insufficiency and interventricular septal shift could be observed in PH-LHD model rats, and the right ventricular systolic pressure (RVSP) and mean left atrial pressure (mLAP) were also elevated in PH-LHD model rats. Meanwhile, we found that MMP-9 and TGF-β1 could be highly expressed in PH-LHD model rats. Besides, we revealed that stretch-activated channel (SAC)/mitogen-activated protein kinases (MAPKs) signaling pathway could be involved in the upregulations of MMP-9 and TGF-β1 mediated by mechanical stretching in pulmonary vein. Therefore, current research revealed that mechanical stretching induced the increasing expressions of MMP-9 and TGF-β1 in pulmonary vein, which could be mediated by activation of SAC/MAPKs signaling pathway in the early stage of PH-LHD.

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“…The rat aortic rings were collected and intervened by stretch stress according to our previously published study [ 3 ]. Briefly, the aortic vessels were cut into 4 mm ring segments and removed the adventitia and intima.…”

Section: Methodsmentioning

confidence: 99%

“…Aortic dissection (AD) is one of the most dangerous aortic diseases [ 1 ]. Although certain therapeutic benefits have been achieved on the clinical diagnosis and treatment of AD by constantly updated and improved surgical techniques [ 2 ], the mortality and the incidence rate of surgical complications are rising due to unclear pathological mechanism [ 3 ]. The deep investigation on the pathogenesis of AD and the analysis on the prognosis of disease are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

C/EBPα-Mediated Transcriptional Activation of PIK3C2A Regulates Autophagy, Matrix Metalloproteinase Expression, and Phenotypic of Vascular Smooth Muscle Cells in Aortic Dissection

Lü

Chen

et al. 2022

Journal of Immunology Research

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Purpose. To investigate the function of C/EBPα in the development of aortic dissection (AD) and the underlying mechanism. Methods. Aortic vascular smooth muscle cells (VSMCs) were isolated, cultured, and identified from AD rats. Then, C/EBPα and PIK3C2A were knockdown or overexpressed by siRNA or plasmid transfection, respectively. Rapamycin or 3-MA was utilized to stimulate and restrain autophagy of VSMCs, respectively. Western blot was used to evaluate the expression levels of C/EBPα, PIK3C2A, LC3, Beclin-1, p62, MMP-2, MMP-9, α-SMA, SM-MHC, and OPN. The pathological status of aortic ring was evaluated by stretch stress, and ChIP assay was used to analyze the binding between C/EBPα and PIK3C2A. C/EBPα shRNA was injected into tail vein to observe the effect of C/EBPα knockdown in vivo on phenotype, autophagy of aortic vascular tissue by immunohistochemical staining and Western blot. Results. The protein levels of C/EBPα, PIK3C2A, MMP-2, MMP-9, and LC3 in the aorta of AD rats were all upregulated significantly. C/EBPα and rapamycin promoted notable upregulation of the synthesized proteins (OPN), PIK3C2A, matrix metalloproteinases, LC3, and Beclin-1 in VSMCs, while suppressed contractile proteins (α-SMA and SM-MHC) and p62. The opposite results were observed in the C/EBPα-knockdown VSMCs, PIK3C2A-knockdown VSMCs, or VSMCs treated with 3-MA. C/EBPα, PIK3C2A, and LC3 were dramatically upregulated by the stimulation of 3 g and 5 g stretch stress. The downregulated contractile proteins, upregulated synthetic proteins, activated autophagy, and aggravated pathological state in 5 g stretch stress-treated aortic rings were significantly reversed by the knockdown of C/EBPα. ChIP results indicated that there was a binding site for C/EBPα in the promoter of PIK3C2A. C/EBPα also downregulated α-SMA level and upregulated OPN levels in AD rats in vivo. Conclusion. Our data indicated that during the development of AD, C/EBPα regulated the transition of VSMC phenotype and extracellular matrix remodeling by activating autophagy through regulating the transcriptional activity of PIK3C2A promoter.

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Mechanical Strain Induced Expression of Matrix Metalloproteinase-9 via Stretch-Activated Channels in Rat Abdominal Aortic Dissection

Cited by 10 publications

References 25 publications

Mechanical stretching of the pulmonary vein mediates pulmonary hypertension due to left heart disease by regulating SAC/MAPK pathway and the expression of IL-6 and TNF-α

Mechanical stretching of the pulmonary vein mediates pulmonary hypertension due to left heart disease by regulating SAC/MAPK pathway and the expression of IL-6 and TNF-α

Mechanical stretching of pulmonary vein stimulates matrix metalloproteinase-9 and transforming growth factor-β1 through stretch-activated channel/MAPK pathways in pulmonary hypertension due to left heart disease model rats

C/EBPα-Mediated Transcriptional Activation of PIK3C2A Regulates Autophagy, Matrix Metalloproteinase Expression, and Phenotypic of Vascular Smooth Muscle Cells in Aortic Dissection

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