Potassium dehydroandrographolide succinate regulates the MyD88/CDH13 signaling pathway to enhance vascular injury-induced pathological vascular remodeling / 中国天然药物

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.

Terpine-4-ol on inhibiting vascular smooth muscle cell calcification by improving mitochondrial dynamics / 药学学报

The aim of this study was to investigate the role and mechanism of terpinen-4-ol (T4O) on high glucose (HG) -induced calcification in vascular smooth muscle cell (VSMC). To investigate the role of T4O on HG-induced calcium deposition, osteogenic phenotypic transformation and mitochondrial dynamics in VSMC, Mdivi-1, a mitochondrial dynamin-related protein 1 (Drp-1) inhibitor, was used to analyze the correlation between mitochondrial dynamics and VSMC calcification and the role of T4O. Alizarin red S staining was used to observe calcium salt deposition and flow cytometry to detect intracellular Ca2+ content; Western blot and immunofluorescence were used to detect the expression of phenotypic switching-related markers α-smooth muscle actin (α-SMA), bone morphogenetic protein 2 (BMP2) and Runt related transcription factor 2 (Runx2), and mitochondrial dynamics-related markers mitofusin 1 (MFN1), mitofusin 2 (MFN2) and Drp-1. The results showed that low and high doses of T4O could inhibit HG-induced down-regulation of α-SMA, MFN1 and MFN2 expression levels, and up-regulation of BMP2, Runx2 and Drp-1 expression levels, reduce intracellular Ca2+ content and calcium salt deposition, and effectively inhibit HG-induced VSMC calcification and mitochondrial dynamics disorders. The T4O group, Mdivi-1 group and T4O+Mdivi-1 group were able to up-regulate the expression levels of HG-induced α-SMA, MFN1 and MFN2, down-regulate the protein expression levels of BMP2, Runx2 and Drp-1, and inhibit calcium salt deposition, and there was no significant difference between the above indexes in the T4O and T4O+Mdivi-1 groups. The above findings suggest that T4O can inhibit the expression level of Drp-1, regulate the disturbance of mitochondrial dynamics, and suppress HG-induced VSMC calcification.

Impact of the transforming growth factor-β pathway on vascular restenosis and its mechanism / 中南大学学报(医学版)

As a crucial regulatory molecule in the context of vascular stenosis, transforming growth factor-β (TGF-β), plays a pivotal role in its initiation and progression. TGF-β, a member of the TGF-β superfamily, can bind to the TGF-β receptor and transduce extracellular to intracellular signals through canonical Smad dependent or noncanonical signaling pathways to regulate cell growth, proliferation, differentiation, and apoptosis. Restenosis remains one of the most challenging problems in cardiac, cerebral, and peripheral vascular disease worldwide. The mechanisms for occurrence and development of restenosis are diverse and complex. The TGF-β pathway exhibits diversity across various cell types. Hence, clarifying the specific roles of TGF-β within different cell types and its precise impact on vascular stenosis provides strategies for future research in the field of stenosis.

A nonobstructive condition: Medial arterial calcification / 中南大学学报(医学版)

Vascular calcification, including intimal and medial calcification, is closely associated with a significant increase in cardiovascular diseases. Although increased understandings were achieved, people still know much more about intimal calcification than medial calcification because the latter doesn't obstruct the arterial lumen, commonly considered as a non-significant finding. We clarified the pathologic characteristic of medial calcification, its difference from intimal calcification, principally focused on its clinical relevance, such as diagnosis, nosogenesis, and hemodynamics. We underline the importance of identifying and distinguishing medial calcification, understanding its effect to local/systematic arterial compliance, and relationship to diabetic neuropathy. Recent studies emphasize do not ignore its predictive role in cardiovascular mortality. It is of great clinical significance to summarize the mechanisms of occurrence, lesion characteristics, diagnostic methods, pathogenic mechanisms, hemodynamic changes, and the distinction as well as association of intimal calcification with intimal calcification.

Vitamin D receptor (VDR) mediates the quiescence of activated hepatic stellate cells (aHSCs) by regulating M2 macrophage exosomal smooth muscle cell-associated protein 5 (SMAP-5) / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.

Protective mechanism of salvianolic acid B on blood vessels / 中国中药杂志

Salvianolic acid B(Sal B) is the main water-soluble component of Salvia miltiorrhiza Bunge. Studies have found that Sal B has a good protective effect on blood vessels. Sal B can protect endothelial cells by anti-oxidative stress, inducing autophagy, inhibiting endoplasmic reticulum stress(ERS), inhibiting endothelial inflammation and adhesion molecule expression, inhibiting endothelial cell permeability, anti-thrombosis, and other ways. In addition, Sal B can alleviate endothelial cell damage caused by high glucose(HG). For vascular smooth muscle cell(VSMC), Sal B can reduce the synthesis and secretion of inflammatory factors by inhibiting cyclooxygenase. It can also play a vasodilatory role by inhibiting Ca~(2+) influx. In addition, Sal B can inhibit VSMC proliferation and migration, thereby alleviating vascular stenosis. Sal B also inhibits lipid deposition in the subendothelium, inhibits macrophage conversion to foam cells, and reduces macrophage apoptosis, thereby reducing the volume of subendothelial lipid plaques. For some atherosclerosis(AS) complications, such as peripheral artery disease(PAD), Sal B can promote angiogenesis, thereby improving ischemia. It should be pointed out that the conclusions obtained from different experiments are not completely consistent, which needs further research. In addition, previous pharmacokinetics showed that Sal B was poorly absorbed by oral administration, and it was unstable in the stomach, with a large first-pass effect in the liver. Sal B had fast distribution and metabolism in vivo and short drug action time. These affect the bioavailability and biological effects of Sal B, and the development of clinically valuable Sal B non-injectable delivery systems remains a great challenge.

Preliminary Results of Single-cell Transcriptome Sequencing in Renal Arterial Lesions of Takayasu Arteritis / 中国医学科学院学报

Objective To explore the preliminary application of single-cell RNA sequencing (scRNA-seq) in the renal arterial lesions in Takayasu arteritis (TA) patients. Methods This study included 2 TA patients with renal artery stenosis treated by bypass surgery in the Department of Vascular Surgery,Beijing Hospital.The obtained 2 renal artery samples were digested with two different protocols (GEXSCOPE kit and self-made digestion liquid) before scRNA-seq and bioinformatics analysis. Results A total of 2920 cells were obtained for further analysis.After unbiased cluster analysis,2 endothelial cell subsets,2 smooth muscle cell subsets,1 fibroblast subset,2 mononuclear macrophage subsets,1 T cell subset,and 1 undefined cell subset were identified.Among them,the two subsets of smooth muscle cells were contractile and secretory,respectively.The results of scRNA-seq indicated that enzymatic hydrolysis with GEXSCOPE kit produced a large number of endothelial cells (57.46%) and a small number of immune cells (13.21%).However,immune cells (34.64%) were dominant in the cells obtained by enzymatic hydrolysis with self-made digestive liquid. Conclusion scRNA-seq can be employed to explore the cellular heterogeneity of diseased vessels in TA patients.Different enzymatic digestion protocols may impact the proportion of different cells.

Role of nicotinamide phosphoribosyltransferase in delaying smooth muscle cell senescence and protecting abdominal aortic aneurysm / 中华危重病急救医学

Objective:To investigate the protective effect of nicotinamide phosphoribosyltransferase (NAMPT) on abdominal aortic aneurysm by delaying the senescence of aortic vascular smooth muscle cells (VSMC).Methods:The primary VSMC cells from normal and patients with abdominal aortic aneurysm were cultured by tissue adherence method. Cells were divided into normal human-derived VSMC group (Ctrl-VSMC group), abdominal aortic aneurysm patient-derived VSMC group (AAA-VSMC group), and angiotensinⅡ(AngⅡ) in vitro abdominal aortic aneurysm model group (AngⅡ-VSMC group, 100 nmol/L AngⅡ treated normal human-derived VSMC for 48 hours), AngⅡ+P7C3 group and AAA+P7C3 group after NAMPT agonist P7C3 intervention (adding 5 μmol/L P7C3 on the basis of AngⅡ-VSMC group and AAA-VSMC group, respectively). Immunofluorescence staining was used to identify VSMC; cell proliferation-associated antigen Ki67 staining was used to detect cell proliferation; senescence associated β-galactosidase (SA-β-gal) staining was used to detect cell senescence in each group; Western blotting was used to detect the protein expression levels of senescence-related proteins p21, p16 and NAMPT in each group. Results:Compared with the Ctrl-VSMC group, the positive rate of SA-β-gal staining and the expression levels of senescence-related proteins p21 and p16 in the AAA-VSMC group and AngⅡ-VSMC group were significantly increased [SA-β-gal staining positive rate: (74.1±4.4)%, (68.6±5.5)% vs. (36.8±10.3)%, p21/GAPDH: 0.61±0.07, 0.51±0.03 vs. 0.31±0.03, p16/GAPDH: 0.77±0.03, 0.72±0.06 vs. 0.33±0.26, all P < 0.01]. However, the expression of NAMPT was significantly decreased (NAMPT/GAPDH: 0.88±0.07, 0.79±0.14 vs. 1.29±0.02, both P < 0.01). Compared with the AngⅡ-VSMC group, the positive rate of SA-β-gal staining and the expressions levels of senescence-related proteins p21 and p16 in the AngⅡ+P7C3 group were significantly lower [SA-β-gal staining positive rate: (49.1±3.2)% vs. (68.6±5.5)%, p21/GAPDH: 0.35±0.06 vs. 0.51±0.03, p16/GAPDH: 0.47±0.08 vs. 0.72±0.06, all P < 0.05], while the expression of NAMPT was significantly increased (NAMPT/GAPDH: 1.15±0.06 vs. 0.79±0.14, P < 0.01). Compared with the AAA-VSMC group, the positive rate of SA-β-gal staining and the expression levels of senescence-related proteins p21 and p16 in the AAA+P7C3 group were significantly lower [SA-β-gal staining positive rate: (54.1±6.0)% vs. (74.1±4.4)%, p21/GAPDH: 0.38±0.02 vs. 0.61±0.07, p16/GAPDH: 0.50±0.13 vs. 0.77±0.03, all P < 0.05], but the expression of NAMPT was significantly increased (NAMPT/GAPDH: 1.25±0.28 vs. 0.88±0.07, P < 0.01). Conclusion:NAMPT agonist P7C3 can delay the senescence of VSMC and play a protective role in abdominal aortic aneurysm.

Treatment of pulmonary hypertension based on inhibition of pulmonary vascular cell proliferation / 药学学报

Pulmonary hypertension is a rapidly progressing disease of the lung vasculature with poor prognosis, ultimately leading to right heart failure and death. The remodeling of small pulmonary arteries represents an important pathological characteristic of pulmonary hypertension. Pulmonary arterial smooth muscle cells (PASMCs) located in the middle layer of pulmonary artery exhibit hyperproliferation and resistance to apoptosis, which is the main initiator of pulmonary vascular remodeling and similar to that seen in tumor cells. In this review we focus on the signaling pathways that play a key role in PASMCs proliferation and the latest research progress on inhibitors targeting cell proliferation pathways to provide a new perspective for the treatment of PH．

The substitution of SERCA2 redox cysteine 674 promotes pulmonary vascular remodeling by activating IRE1α/XBP1s pathway

Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling, in which hyperproliferation of pulmonary artery smooth muscle cells (PASMCs) plays an important role. The cysteine 674 (C674) in the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) is the critical redox regulatory cysteine to regulate SERCA2 activity. Heterozygous SERCA2 C674S knock-in mice (SKI), where one copy of C674 was substituted by serine to represent partial C674 oxidative inactivation, developed significant pulmonary vascular remodeling resembling human PH, and their right ventricular systolic pressure modestly increased with age. In PASMCs, substitution of C674 activated inositol requiring enzyme 1 alpha (IRE1α) and spliced X-box binding protein 1 (XBP1s) pathway, accelerated cell cycle and cell proliferation, which reversed by IRE1α/XBP1s pathway inhibitor 4μ8C. In addition, suppressing the IRE1α/XBP1s pathway prevented pulmonary vascular remodeling caused by substitution of C674. Similar to SERCA2a, SERCA2b is also important to restrict the proliferation of PASMCs. Our study articulates the causal effect of C674 oxidative inactivation on the development of pulmonary vascular remodeling and PH, emphasizing the importance of C674 in restricting PASMC proliferation to maintain pulmonary vascular homeostasis. Moreover, the IRE1α/XBP1s pathway and SERCA2 might be potential targets for PH therapy.

Isoflurane Inhibits Pyroptosis of Human Pulmonary Artery Smooth Muscle Cells Through the Nrf2/HO⁃1/ROS Pathway / 中国生物化学与分子生物学报

Previous studies have demonstrated that isoflurane inhale anesthesia can effectively attenuate the ischemia-reperfusion-induced pulmonary hypertension (PAH), indicating a protective effect of isoflurane on pulmonary circulation. Pulmonary artery smooth muscle cells (PASMCs) play an important role in pulmonary vascular remodeling and PAH. The abnormality of PASMC structure and function may greatly contribute to the development of PAH. This study aims to explore the effects of isoflurane on hypoxia-induced PASMC pyroptosis and the underlying mechanisms, and to find potential therapeutic target for the treatment of PAH. PASMCs were cultured at 37 ℃, 5%CO

Research progress on therapeutic strategies for improving pulmonary vascular remodeling in pulmonary hypertension / 中国药理学通报

Pulmonary hypertension(PH)is a chronic,progressive,high-mortality disease characterized by a continuous increase in pulmonary vascular pressure. All types of PH have the same characteristics,i.e.,the excessive proliferation,anti-apoptosis and inflammation of pulmonary artery endothelial cells and smooth muscle cells,which leads to progressive thickening of pulmonary small vessels,resulting in pulmonary vascular remodeling and increased pulmonary vascular resistance,ultimately leading to right ventricular hypertrophy,heart failure,and death. The drugs used to treat PH mainly include L-type calcium channel blockers,phosphodiesterase 5 inhibitors,guanosine cyclase activators,endothelin receptor antagonists,and synthetic prostacyclin and its analogues. These drugs reduce pulmonary artery pressure by relaxing pulmonary blood vessels but do not cure the patient,and their prognosis remains poor. Therefore,the development of drugs that can effectively improve or even reverse pulmonary vascular remodeling is the key to treating PH. In recent years,studies on pulmonary vascular remodeling mainly included(1)the synthesis of new small-molecule compounds;(2)the transformation of mature drugs,such as the use of drug combinations and dosage form transformation,etc.;(3)the pharmacodynamic evaluation of traditional Chinese medicines and derived compounds based on the theory of "lung distension";(4)research into monomers of traditional Chinese medicine; and(5)research into new targets.

Effects of notoginsenoside R1 on AngⅡ induced proliferation of MOVAS cells and AT1R/MAPKs signaling pathway / 上海预防医学

Objective:To investigate the effects of notoginsenoside R1 （NR1） on the proliferation of mice aortic smooth muscle cells （MOVAS cells） induced by angiotensinⅡ （AngⅡ） and the signal pathway of angiotensin Ⅱ type 1 receptor （AT1R） / mitogen activated protein kinases （MAPKs）. Methods:The proliferation of MOVAS cells was detected by BrdU method after AngⅡ induction. Western blot was used to detect the expression of the two main receptors of AngⅡ （AT1R and AT2R） and MAPKs pathway related proteins （ERK， p38， and JNK）. Results:（1） AngⅡ （5 μmol/L） could promote the proliferation of MOVAS cells （P<0.01）. NR1 （50 μmol/L） could inhibit the proliferation of MOVAS cells induced by AngⅡ （P<0.01）. There was no significant difference between control group and NR1 group （P>0.05）. （2） Compared with AngⅡ group， the expression of AT1R protein in AngⅡ+ NR1 group was significantly lower （P<0.05）， but there was no difference in the expression of AT2R protein （P>0.05）. （3） NR1 could significantly inhibit the phosphorylation of ERK， p38 and JNK protein after AngⅡ stimulation （P<0.01）. Conclusion:NR1 can inhibit the proliferation of MOVAS cells induced by AngⅡ， which may be related to down regulating AT1R and inhibiting the activation of MAPKs.

Research advance of Nrf2 on atherosclerosis by regulating vascular smooth muscle cell / 浙江大学学报·医学版

Atherosclerosis is a common pathological change in cardiovascular disease. Vascular smooth muscle cell is the main source of plaque cell and extracellular matrix, and nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating the function of vascular smooth muscle cell. In the process of atherosclerosis, Nrf2 signaling pathway has the following regulatory effects on vascular smooth muscle cell: regulating the phenotype of vascular smooth muscle cell to change to the direction conducive to the alleviation of disease progression; inhibiting the proliferation and migration of vascular smooth muscle cell; mitigating the level of blood lipid; alleviating vascular smooth muscle cell calcification, aging and apoptosis process. This article reviews the specific mechanisms of Nrf2 regulating atherosclerosis, such as phenotypic transformation, proliferation and migration, lipid metabolism, calcification, aging and apoptosis in atherosclerosis, in order to provide a basis for understanding the molecular mechanism of atherosclerosis development and finding therapeutic targets.

Functional role and underlying mechanisms of neuropilin-1 in proliferation and migration of rat vascular smooth muscle cells / 中国胸心血管外科临床杂志

@#Objective    To investigate the role and potential mechanisms of neuropilin-1 (NRP1) in the pathogenesis of vein graft failure. Methods    The rat vascular smooth muscle cells (VSMCs) were transfected with NRP1-shRNA adenovirus and negative control adenovirus respectively. Cell counting kit-8, flow cytometry, Transwell and Western blot were used to investigate the effects of inhibition of NRP1 on VSMCs proliferation viability, apoptosis, migration capacity and its downstream signaling pathway protein expression. Results    The proliferation and migration of rat VSMCs could be inhibited after down-regulation of NRP1, and the increase of apoptosis was also observed. Moreover, inhibition of NRP1 significantly reduced Akt and NF-κB phosphorylation in rat VSMCs, but had little effect on activation of ERK1/2. Conclusion    NRP1 may promote vein graft hyperplastic remodeling by regulating the proliferation and migration of VSMCs through PI3K/Akt and NF-κB pathways, but further animal study is required.

Research progress on correlation between lncRNAs and pathogenesis of vascular diseases / 中国职业医学

Occupational hand-arm vibration diseases(HAVD) is a legitimate occupational disease in China, and the mechanism of its pathogenesis is vibration-induced vascular injury. Once HAVD occurs, it is difficult for the patients to recover and can cause great harm to workers exposed to hand-arm vibration. It is difficult to detect and evaluate the occurrence and progress of the disease at an early stage using existing technology, which is disadvantageous to the early prevention and treatment of the disease. Long noncoding RNAs(lncRNAs) play an important role in regulating the development, growth, and remodeling of blood vessels and other biological processes. This article reviews the role and mechanism of lncRNAs in vascular injury, and provides scientific theoretical basis for early diagnosis and treatment of HAVD.

Knockdown of WDR1 Inhibits Nuclear Translocation of STAT3 to Regulate Smooth Muscle Cell Proliferation and Migration / 中国生物化学与分子生物学报

Nuclear transport of signal transducer and activator of transcription 3 (STAT3) is a prerequisite for its biological function. WD Repeat domain 1 (WDR1), a regulator of the cytoskeleton factors, may affect STAT3 nuclear translocation. However, the molecular mechanism regarding the effect of WDR1 on STAT3 nuclear translocation is still unknown. To investigate the effect of WDR1 on STAT3 nuclear translocation in smooth muscle cells, a human aortic vascular smooth muscle cells (HAVSMCs) model with stable knockdown of WDR1 was constructed. The results of RT-qPCR and Western blot showed that the activation and expression of STAT3 were not significantly altered after knockdown of Wdr1 (P>0. 05); the results of nucleoplasm isolation showed that the nucleoplasm distribution of STAT3 was significantly affected after knockdown of WDR1 compared with the control group. Subsequent results showed that the expression of STAT3 nuclear input-associated protein β (importin β) was inhibited (P < 0. 05) and the nucleoplasmic ratio of Ras-associated nuclear protein (Ran) was significantly decreased compared to the control group. Results from CCK8 and Transwell assays indicated that overexpression of importin β was able to rescue the inhibition of proliferation and migration of HAVSMCs caused by WDR1 knockdown. Further results showed that knockdown of WDR1 resulted in a significant decrease in the expression of nuclear transport factor 2 (NTF2) associated with the Ran nucleotide cycle (P<0. 05). After overexpression of NTF2, the results of CCK8 and Transwell experiments showed that the proliferation and migration ability of HAVSMCs were significantly enhanced (P < 0. 05). Summarizing the above results, knockdown of WDR1, by inhibiting the expression of importin β and NTF2, alters the nucleoplasmic distribution of Ran and decreases the nuclear translocation of STAT3, thus regulating the proliferation and migration of smooth muscle cells.

Effects of budesonide on proliferation and apoptosis of airway smooth muscle cells in asthmatic rats / 解剖学报

Objective To investigate the effect of budesonide ( BUD) inhalation on the proliferation and apoptosis of airway smooth muscle cells ( ASMCs) in asthmatic rats and its molecular biological mechanism. Methods Totally 40 SD rats were randomly divided into control group, asthma model group, low (0. 25 mg/kg) and high (2 mg/kg) BUD group. The rat asthma model was induced by ovalbumin (VOA) combined with aluminium hydroxide Gel sensitization stimulation. After sensitization, the intervention group inhaled different doses of BUD before stimulation. The related parameters of lung tissue and airway were measured and calculated by medical image analysis system, immunofluorescence was used to detect the expression of type I collagen ( Col I ) and Col III in rat airway smooth muscle ( ASM ), and the protein expressions of Bcl-2, Bax, Caspase-3, phosphorylated ERK 1 and 2(p-ERK 1 / 2), p-p38 MAPK were detected by Western blotting. The proliferation activity of ASMCs was detected by MTT method, and the apoptosis rate of ASMCs was detected by flow cytometry. Results Compared with the control group, airway remodeling occurred in the asthmatic model group, and the airway wall thickness ( WAt/Pbm ), inner wall thickness ( WAi/Pbm ) and smooth muscle thickness ( WAm/Pbm ) increased, compared with the model group, the airway remodeling was inhibited in BUD intervention group, and the tracheal WAt/Pbm, WAi/Pbm and WAm/Pbm decreased in bud treatment group. BUD could decrease the proliferation activity of ASMCs, increase the apoptosis rate of ASMCs, inhibit the expression of Col I and Col III, deregulate the expression of Bcl-2, upregulate the expression of Bax and Caspase-3 ( all P<0. 05), and inhibit the activity of ERK 1/2 and p38 MAPK signal pathway. Conclusion BUD can inhibit the proliferation and the promote apoptosis of ASMCs in asthmatic rats, which may be related to the inhibition of ERK 1/2 and p38 MAPK signal pathways.

Role of calcium sensing receptors in proliferation and migration of renal artery smooth muscle cells under insulin resistance / 中国药理学通报

To investigate the role and mechanism of calcium-sensing receptor (CaSR) in the proliferation and migration of renal artery smooth muscle cells (RASMCs) under insulin resistance. Methods RAMSCs in the logarithmic growth stage were randomly divided into control, pure model, model + GdCl

Quercetin-induced apoptosis ameliorates vascular smooth muscle cell senescence through AMP-activated protein kinase signaling pathway

Aging is one of the risk factors for the development of cardiovascular diseases. During the progression of cellular senescence, cells enter a state of irreversible growth arrest and display resistance to apoptosis. As a flavonoid, quercetin induces apoptosis in various cells. Accordingly, we investigated the relationship between quercetin-induced apoptosis and the inhibition of cellular senescence, and determined the mechanism of oxidative stress-induced vascular smooth muscle cell (VSMC) senescence. In cultured VSMCs, hydrogen peroxide (H₂O₂) dose-dependently induced senescence, which was associated with increased numbers of senescence-associated β-galactosidase-positive cells, decreased expression of SMP30, and activation of p53-p21 and p16 pathways. Along with senescence, expression of the anti-apoptotic protein Bcl-2 was observed to increase and the levels of proteins related to the apoptosis pathway were observed to decrease. Quercetin induced apoptosis through the activation of AMP-activated protein kinase. This action led to the alleviation of oxidative stress-induced VSMC senescence. Furthermore, the inhibition of AMPK activation with compound C and siRNA inhibited apoptosis and aggravated VSMC senescence by reversing p53-p21 and p16 pathways. These results suggest that senescent VSMCs are resistant to apoptosis and quercetin-induced apoptosis attenuated the oxidative stress-induced senescence through activation of AMPK. Therefore, induction of apoptosis by polyphenols such as quercetin may be worthy of attention for its anti-aging effects.