Ligustrazine activate the PPAR-γ pathway and play a protective role in vascular calcification

Vascular ◽  
2021 ◽  
pp. 170853812110514
Author(s):  
Hui Li ◽  
Min Yang
Keyword(s):  
Vascular Calcification ◽  
Chondrogenic Differentiation ◽  
Calcium Content ◽  
Protective Role ◽  
Peroxisome Proliferation ◽  
Rt Pcr ◽  
Alizarin Red ◽  
Ppar Γ ◽  
Related Proteins

Objective The purpose of this study was to explore the role of ligustrazine in vascular calcification. Methods After β-GP stimulation, vascular smooth muscle cells (VSMCs) were detected by Alizarin Red Staing staining. Calcium content and alkaline phosphatase (ALP) activity were detected by intracellular calcium assay kit and ALP assay kit, respectively. The expression of peroxisome proliferation-activated receptor (PPAR-γ) pathway–related proteins was detected by Western blot. PPAR-γ, MSX2, osteopontin (OPN), sclerostin, and BGP were detected by RT-PCR. Results β-GP induced the decreased activity and expression of PPAR-γ and ALP in VSMCs, while ligustrazine activated the expression of PPAR-γ. Through activation of PPAR-γ, ligustrazine decreased β-GP–induced VSMC calcification, decreased the expression of markers of osteogenesis and chondrogenic differentiation, and increased the expression of VSMC markers. Conclusion Ligustrazine activates the PPAR-γ pathway and plays a protective role in vascular calcification.

scholarly journals Antidiabetic Drugs in NAFLD: The Accomplishment of Two Goals at Once?

2018 ◽  
Vol 11 (4) ◽  
pp. 121 ◽  
Author(s):  
Matteo Tacelli ◽  
Ciro Celsa ◽  
Bianca Magro ◽  
Aurora Giannetti ◽  
Grazia Pennisi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Meta Analysis ◽  
Pancreatic Beta Cell ◽  
Protective Role ◽  
Antidiabetic Drugs ◽  
Alcoholic Fatty Liver ◽  
Compensated Cirrhosis ◽  
Ppar Γ ◽  
Insulin Use

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease in Western countries, accounting for 20–30% of general population and reaching a prevalence of 55% in patients with type 2 diabetes mellitus (T2DM). Insulin resistance plays a key role in pathogenic mechanisms of NAFLD. Many drugs have been tested but no medications have yet been approved. Antidiabetic drugs could have a role in the progression reduction of the disease. The aim of this review is to summarize evidence on efficacy and safety of antidiabetic drugs in patients with NAFLD. Metformin, a biguanide, is the most frequently used drug in the treatment of T2DM. To date 15 randomized controlled trials (RCTs) and four meta-analysis on the use of metformin in NAFLD are available. No significant improvement in histological liver fibrosis was shown, but it can be useful in the treatment of co-factors of NAFLD, like body weight, transaminase or cholesterol levels, and HbA1c levels. A possible protective role in various types of cancer has been reported for Metformin. Thiazolidinediones modulate insulin sensitivity by the activation of PPAR-γ. The RCTs and the meta-analysis available about the role of these drugs in NAFLD show an improvement in ballooning, lobular inflammation, and perhaps fibrosis, but some side effects, in particular cardiovascular, were showed. GLP-1 analogues stimulate insulin secretion by pancreatic beta cell and inhibit glucagon release; Liraglutide is the most used drug in this class and significantly improves steatosis, hepatocyte ballooning and transaminase levels. Scanty data about the role of DPP-4 and SGLT inhibitors were published. No data about insulin effects on NAFLD are available but it was showed a possible association between insulin use and the development of solid neoplasms, in particular HCC. In conclusion, antidiabetic drugs seem to be promising drugs, because they are able to treat both NAFLD manifestations and diabetes, preventing worsening of hepatic damage, but data are still conflicting. All antidiabetic drugs can be safely used in patients with compensated cirrhosis, while insulin is the preferred drug in decompensated Child C cirrhosis.

scholarly journals Triptolide Attenuates Vascular Calcification by Upregulating Expression of miRNA-204

2021 ◽  
Vol 11 ◽  
Author(s):  
Yu-qiang Pei ◽  
Yong-qiu Zheng ◽  
Yao-dong Ding ◽  
Qi-xiang Xu ◽  
Di Cao ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Molecular Mechanisms ◽  
Therapeutic Option ◽  
Calcium Content ◽  
Rat Aorta ◽  
Protective Role ◽  
Bone Morphogenetic Protein 2 ◽  
Dependent Manner ◽  
Protective Effects ◽  
Alp Activity

Background: Triptolide (TP), a naturally derived compound from Tripterygium wilfordii, has been proven effective in protecting against cardiovascular system, but the molecular mechanisms underlying its protective effects are poorly understood. In the current study, we sought to test the potential protective role of TP in the regulation of vascular calcification in a rat model and explore whether TP attenuates medial vascular calcification by upregulating miRNA-204.Methods: Vitamin D3 plus nicotine (VDN) was used to induce a vascular calcification (VC) model of rat aorta. Von Kossa and Hematoxylin-Eosin staining were applied to assess the degree of calcification of rat aortas. Calcium content and alkaline phosphatase activity were measured. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was applied to quantify miRNA-204 expression. The localization of runt-related transcription factor-2 (RUNX2) and bone morphogenetic protein-2 (BMP2) expressions were detected by immunohistochemistry and western blotting.Results: Administration of TP greatly reduced vascular calcification in a dose-dependent manner compared with VC controls. The increase in ALP activity and calcium content was ameliorated by TP. Moreover, protein expression levels of BMP2 and RUNX2 were significantly reduced in calcified aortas. MiRNA-204 expression was increased in the TP-treated groups compared with VC controls and the effects of TP were reversed by the intravenous injection of miRNA-204-interfering lentivirus. However, the miRNA-204-overexpressing lentivirus had no additional effects on ALP activity, calcium content, BMP2 and RUNX2 expressions compared with those from TP group.Conclusion: TP inhibited BMP2 and RUNX2 expression and attenuated vascular calcification via upregulating the level of miRNA-204. TP appears to be a potential new therapeutic option for treating vascular calcification.

scholarly journals On Cancer, COVID-19, and CT Scans: A Monocentric Retrospective Study

2020 ◽  
Vol 9 (12) ◽  
pp. 3935
Author(s):  
Francesca Martini ◽  
Andrea D’Alessio ◽  
Federico Bracchi ◽  
Daniela Di Mauro ◽  
Anna Fargnoli ◽  
...  
Keyword(s):  
Severe Disease ◽  
Protective Role ◽  
Northern Italy ◽  
Chest Ct ◽  
Ct Scans ◽  
Rt Pcr ◽  
Cardiovascular Comorbidities ◽  
Oncological Patients ◽  
High Incidence

Background The use of computed tomography (CT) for coronavirus disease 2019 (COVID-19) diagnosis in an area of northern Italy with a high incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may have identified more patients with this disease than RT-PCR in the very early onset of the COVID-19 pandemic. Methods We retrospectively reviewed 148 chest CT scans of oncological patients who were referred to the Radiological Unit of Policlinico S. Marco from 1 February 2020 to 30 April 2020, during the COVID-19 outbreak in Bergamo area. In parallel, we analyzed RT-PCR tests of these 148 patients. Results Among 32 patients with a diagnosis of COVID-19, 17 patients were asymptomatic or had mild symptoms (53.1%), while 15 developed severe disease (46.8%). The incidence of SARS-CoV-2 infection was 22.9%, the mortality rate was 18.8%. We did not find any correlation between disease severity and age, sex, smoking, or cardiovascular comorbidities. Remarkably, patients who were on treatment for cancer developed a milder disease than patients who were not on treatment. Conclusions The acceptance of CT-defined diagnoses in COVID-19 high-incidence areas like Bergamo region highlighted a larger oncological population affected by COVID-19 than RT-PCR, in particular, asymptomatic and mildly symptomatic patients, because only symptomatic patients underwent nasopharyngeal swabbing at the onset of the COVID-19 pandemic. We observed that patients actively treated for their cancer had a milder disease, in agreement with previous studies that suggested a protective role of immunosuppression. Admittedly, the sample of patients in our study was heterogeneous regarding the oncological disease, their prognosis, and the type of treatment; therefore, other studies are needed to confirm our data.

scholarly journals Autophagy plays a protective role during Pseudomonas aeruginosa-induced apoptosis via ROS–MAPK pathway

2020 ◽  
Vol 26 (7) ◽  
pp. 580-591
Author(s):  
Lu Han ◽  
Qinmei Ma ◽  
Jialin Yu ◽  
Zhaoqian Gong ◽  
Chenjie Ma ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Mapk Pathway ◽  
Protective Role ◽  
Vital Role ◽  
Raw264.7 Cells ◽  
Cellular Reactive Oxygen Species ◽  
Induced Apoptosis ◽  
Related Proteins ◽  
The Impact

Pseudomonas aeruginosa infection can induce alveolar macrophage apoptosis and autophagy, which play a vital role in eliminating pathogens. These two processes are usually not independent. Recently, autophagy has been found to interact with apoptosis during pathogen infections. Nevertheless, the role of autophagy in P. aeruginosa-infected cell apoptosis is unclear. In this study, we explored the impact of P. aeruginosa infection on autophagy and apoptosis in RAW264.7 cells. The autophagy activator rapamycin was used to stimulate autophagy and explore the role of autophagy on apoptosis in P. aeruginosa-infected RAW264.7 cells. The results indicated that P. aeruginosa infection induced autophagy and apoptosis in RAW264.7 cells, and that rapamycin could suppress P. aeruginosa-induced apoptosis by regulating the expression of apoptosis-related proteins. In addition, rapamycin scavenged the cellular reactive oxygen species (ROS) and diminished p-JNK, p-ERK1/2 and p-p38 expression of MAPK pathways in RAW264.7 cells infected with P. aeruginosa. In conclusion, the promotion of autophagy decreased P. aeruginosa-induced ROS accumulation and further attenuated the apoptosis of RAW264.7 cells through MAPK pathway. These results provide novel insights into host–pathogen interactions and highlight a potential role of autophagy in eliminating P. aeruginosa.

scholarly journals Autophagy Protects Advanced Glycation End Product-Induced Apoptosis and Expression of MMP-3 and MMP-13 in Rat Chondrocytes

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Wenzhou Huang ◽  
Peng Ao ◽  
Jian Li ◽  
Tianlong Wu ◽  
Libiao Xu ◽  
...  
Keyword(s):  
Western Blotting ◽  
Annexin V ◽  
Protective Role ◽  
Autophagic Flux ◽  
Advanced Glycation ◽  
Age Related ◽  
Glycation End Products ◽  
Induced Apoptosis ◽  
Related Proteins

Aging is one of the most prominent risk factors for the pathological progression of osteoarthritis (OA). One feature of age-related changes in OA is advanced glycation end products (AGEs) accumulation in articular cartilage. Autophagy plays a cellular housekeeping role by removing dysfunctional cellular organelles and proteins. However, the relationship between autophagy and AGE-associated OA is unknown. The aim of this study is to determine whether autophagy participates in the pathology of AGE-treated chondrocytes and to investigate the exact role of autophagy in AGE-induced cell apoptosis and expression of matrix metalloproteinase- (MMP-) 3 and MMP-13. AGEs induced notable apoptosis that was detected by Annexin V/PI double-staining, and the upregulation of MMP-3 and MMP-13 was confirmed by Western blotting. Autophagy-related proteins were also determined by Western blotting, and chondrocytes were transfected with mCherry-GFP-LC3B-adenovirus to monitor autophagic flux. As a result, autophagy significantly increased in chondrocytes and peaked at 6 h. Furthermore, rapamycin (RA) attenuated AGE-induced apoptosis and expression of MMP-3 and MMP-13 by autophagy activation. In contrast, pretreatment with autophagy inhibitor 3-methyladenine (3-MA) enhanced the abovementioned effects of AGEs. We therefore demonstrated that autophagy is linked with AGE-related pathology in rat chondrocytes and plays a protective role in AGE-induced apoptosis and expression of MMP-3 and MMP-13.

scholarly journals On Cancer, COVID-19 and CT Scan: A Monocentric Retrospective Study

2020 ◽  
Author(s):  
Francesca Martini ◽  
Andrea D'Alessio ◽  
Federico Bracchi ◽  
Daniela Di Mauro ◽  
Anna Fargnoli ◽  
...  
Keyword(s):  
Severe Disease ◽  
Protective Role ◽  
Northern Italy ◽  
Chest Ct ◽  
Ct Scans ◽  
Rt Pcr ◽  
Cardiovascular Comorbidities ◽  
Oncological Patients ◽  
High Prevalence

Background The acknowledgment of computed tomography (CT) defined diagnosis in high prevalence northern Italy may identify more patients with Coronavirus Disease-2019 (COVID 19) infection, than RT-PCR alone. Methods We retrospectively reviewed 148 chest CT scans of oncological patients who were referred to the Radiological Unit of Policlinico S. Marco from 1st of February 2020 to 30th of April 2020, during the Covid-19 outbreak in Bergamo area. Therefore, we analyzed RT-PCR tests of these 148 patients. Results Among 32 patients with diagnosis of COVID-19 infection: 17 patients were asymptomatic or had mild symptoms (53.1%), while 15 developed severe disease (46.8%). The incidence of COVID-19 infection is 22.9%, the mortality rate is 18.8%. Severe COVID-19 disease is associated with higher median age. We did not find any correlation between disease severity and sex, smoke or cardiovascular comorbidities. Remarkably, patients who were on treatment developed milder disease than cancer patients who were not on treatment. Conclusions The acceptance of CT-defined diagnosis in high prevalence area like Bergamo highlighted a larger number of COVID-19 oncological population than RT-PCR alone, in particular asymptomatic and mild symptomatic patients. We observed that actively treated patients had milder disease, according to previous studies that suggested a protective role of immunosuppression.

MO565M2 MACROPHAGES REGULATE MOUSE AORTIC SMOOTH MUSCLE CELL CALCIFICATION BY TRANSMITTING SENESCENCE INFORMATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Yaping Fang ◽  
Xiaodong Zhu ◽  
Yu Zhao ◽  
Xiao liang Zhang
Keyword(s):  
Smooth Muscle ◽  
Vascular Calcification ◽  
Calcium Content ◽  
M2 Macrophage ◽  
High Morbidity ◽  
M2 Macrophages ◽  
Alizarin Red ◽  
Aortic Smooth Muscle ◽  
Test Kit

Abstract Background and Aims Vascular calcification is highly prevalent in chronic kidney disease (CKD)with high morbidity and mortality. Complex pathological mechanisms are involved in the development of vascular calcification, including aging. Previous work have indicated that M2-macrophage promote mouse aortic smooth muscle cells (MAoSMCs) calcification. The present study aimed to understand the contribution of M2-macrophage to MAoSMCs calcification by focusing on the mechanisms underlying the transmitting senescence information Method The expression of IFITM3 and P16, marker of aging, in aging macrophages were confimed by RT-qPCR, western blotting and immunofluorescence staining. Then, the MAoSMCs were co-cultured with the supernatant of M2 macrophages. The expression of IFITM3 and P16 in MAoSMCs also were detected. Alizarin red staining and calcium content assay were used to analyse MAoSMCs calcification. We modulated the expression of IFITM3 using siRNAs to study M2-macrophages function in regulating MAoSMCs calcification.We detected the expression of IFITM3 and P16 in co-cultivate MAoSMCs and validate intracellular calcium contents by calcium test kit. Results In the present study, we observed a significant increase in the expression of IFITM3 and P16 expression in M2 macrophages.Compared with M0 and M1 macrophages, the expression of IFITM3 and P16 at lowlevel. Alizarin red staining and calcium content assay revealed that M2 macrophage-mediated IFITM3 and P16 overexpression led to an apparent VSMC calcification in the presence of M2 macrophages medium.By contrast, inhibition of IFITM3 by siRNAs significantly blocked calcification of VSMCs in vitro. Moreover, we found that aging macrophages that overexpressed of IFITM3 and P16 increased in rats with CKD. Furthermore, pharmacological inhibition of aging signal was shown to block IFITM3-induced VSMC calcification. These findings demonstrate for the first time that M2 macrophage-mediated IFITM3 contributes to vascular calcification through a mechanism involving transmitting Senescence signalling. Conclusion Collectively, our present study demonstrated that the functional importance of M2 macrophage-IFITM3 dependent vascular calcification and provided a novel mechanistic insight to the macrophage senescence in CKD.

scholarly journals Trimethylamine-N-Oxide Promotes Vascular Calcification Through Activation of NLRP3 (Nucleotide-Binding Domain, Leucine-Rich-Containing Family, Pyrin Domain-Containing-3) Inflammasome and NF-κB (Nuclear Factor κB) Signals

2020 ◽  
Vol 40 (3) ◽  
pp. 751-765 ◽  
Author(s):  
Xiuli Zhang ◽  
Yining Li ◽  
Pingzhen Yang ◽  
Xiaoyu Liu ◽  
Lihe Lu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Smooth Muscle ◽  
Kidney Disease ◽  
Vascular Smooth Muscle ◽  
Vascular Calcification ◽  
Ex Vivo ◽  
Calcium Content ◽  
Nuclear Factor Κb ◽  
Alizarin Red ◽  
Pyrin Domain

Objectives: Vascular calcification is highly prevalent in patients with chronic kidney disease. Increased plasma trimethylamine N-oxide (TMAO), a gut microbiota-dependent product, concentrations are found in patients undergoing hemodialysis. However, a clear mechanistic link between TMAO and vascular calcification is not yet established. In this study, we investigate whether TMAO participates in the progression of vascular calcification using in vitro, ex vivo, and in vivo models. Approach and Results: Alizarin red staining revealed that TMAO promoted calcium/phosphate-induced calcification of rat and human vascular smooth muscle cells in a dose-dependent manner, and this was confirmed by calcium content assay. Similarly, TMAO upregulated the expression of bone-related molecules including Runx2 (Runt-related transcription factor 2) and BMP2 (bone morphogenetic protein-2), suggesting that TMAO promoted osteogenic differentiation of vascular smooth muscle cells. In addition, ex vivo study also showed the positive regulatory effect of TMAO on vascular calcification. Furthermore, we found that TMAO accelerated vascular calcification in rats with chronic kidney disease, as indicated by Mico-computed tomography analysis, alizarin red staining and calcium content assay. By contrast, reducing TMAO levels by antibiotics attenuated vascular calcification in chronic kidney disease rats. Interestingly, TMAO activated NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome and NF-κB (nuclear factor κB) signals during vascular calcification. Inhibition of NLRP3 inflammasome and NF-κB signals attenuated TMAO-induced vascular smooth muscle cell calcification. Conclusions: This study for the first time demonstrates that TMAO promotes vascular calcification through activation of NLRP3 inflammasome and NF-κB signals, suggesting the potential link between gut microbial metabolism and vascular calcification. Reducing the levels of TMAO could become a potential treatment strategy for vascular calcification in chronic kidney disease.

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