scholarly journals A Review of CXCL1 in Cardiac Fibrosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Cheng-Long Wu ◽  
Ran Yin ◽  
Su-Nan Wang ◽  
Ru Ying
Keyword(s):  
Cardiovascular Diseases ◽  
Serum Level ◽  
Inflammatory Reaction ◽  
Cardiac Remodeling ◽  
Recent Progress ◽  
Cardiac Fibrosis ◽  
Elevated Serum ◽  
Inflammatory Factor ◽  
Growing Body

Chemokine C-X-C motif ligand-1 (CXCL1), principally expressed in neutrophils, macrophages and epithelial cells, is a valid pro-inflammatory factor which performs an important role in mediating the infiltration of neutrophils and monocytes/macrophages. Elevated serum level of CXCL1 is considered a pro-inflammatory reaction by the organism. CXCL1 is also related to diverse organs fibrosis according to relevant studies. A growing body of evidence suggests that CXCL1 promotes the process of cardiac remodeling and fibrosis. Here, we review structure and physiological functions of CXCL1 and recent progress on the effects and mechanisms of CXCL1 in cardiac fibrosis. In addition, we explore the role of CXCL1 in the fibrosis of other organs. Besides, we probe the possibility that CXCL1 can be a therapeutic target for the treatment of cardiac fibrosis in cardiovascular diseases.

Abstract MP259: The Role Of Sertad4 In Pathological Cardiac Remodeling

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Matthew Stratton ◽  
Ashley Francois ◽  
Oscar Bermeo-Blanco ◽  
Alessandro Canella ◽  
Lynn Marcho ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Systolic Function ◽  
Myocardial Infarct ◽  
Proteasome Inhibition ◽  
Rna Seq ◽  
Expression Of Genes ◽  
M Phase ◽  
Tgf Β1

Over 6 million Americans suffer from heart failure (HF) while the 5-year mortality rate following first admission for HF is over 40%. Cardiac fibrosis is a clinical hallmark of HF, regardless of the initiating pathology and is thought to contribute to disease progression. Using an epigenomics discovery approach, we uncovered a nuclear protein, Sertad4, as a potential anti-fibrotic target. Our data indicate that Sertad4 is a positive regulator of fibroblast activation. Specifically, cultured cardiac fibroblast experiments demonstrate that Sertad4 targeting with shRNAs blocks fibroblast proliferation and causes cells to arrest in the G2/M phase of the cell cycle. Also, shRNA targeting of Sertad4 dramatically blocked activation of myofibroblast differentiation genes (αSMA/POSTN/COL1A1). Mechanistically, these effects appear to be mediated by Sertad4 regulation of SMAD2 protein stability in the presence of TGF-β1 stimulation as demonstrated by proteasome inhibition experiments. RNA-seq analysis indicate that Sertad4 also regulates the expression of genes involved in ubiquitination and proteasome degradation. Next, we sought to determine the effect of global Sertad4 knockout on post-myocardial infarct (MI) remodeling and cardiac function in mice. After 4 weeks of permanent LAD ligation, echocardiography was performed to measure systolic function. Relative to wild-type (WT) controls, the Sertad4 KO mice showed preserved systolic function as evident by improved ejection fraction (WT 14.4 +/- 3.6 vs. KO 33.9+/-5.9, p=0.035) and fractional shortening (WT 6.5 +/- 1.7 vs. KO 16.4 +/- 3.4, p=0.046). β-gal staining in the Sertad4/LacZ reporter mouse subjected to MI showed robust Sertad4/LacZ expression in the ischemic scar and boarder-zone with almost no expression in control hearts. This data supports the notion that Sertad4 has a key role in cardiac remodeling in response to ischemic injury.

scholarly journals MicroRNA-143/-145 in Cardiovascular Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Wang Zhao ◽  
Shui-Ping Zhao ◽  
Yu-Hong Zhao
Keyword(s):  
Smooth Muscle ◽  
Cardiovascular Diseases ◽  
Vascular Smooth Muscle Cells ◽  
Essential Role ◽  
Recent Progress ◽  
Potential Role ◽  
Phenotypic Switching ◽  
Diagnostic Biomarkers ◽  
Potential Strategy

MicroRNAs (miRNAs) play an essential role in the onset and development of many cardiovascular diseases. Increasing evidence shows that miRNAs can be used as potential diagnostic biomarkers for cardiovascular diseases, and miRNA-based therapy may be a promising therapy for the treatment of cardiovascular diseases. The microRNA-143/-145 (miR-143/-145) cluster is essential for differentiation of vascular smooth muscle cells (VSMCs) and determines VSMC phenotypic switching. In this review, we summarize the recent progress in knowledge concerning the function of miR-143/-145 in the cardiovascular system and their role in cardiovascular diseases. We discuss the potential role of miR-143/-145 as valuable biomarkers for cardiovascular diseases and explore the potential strategy of targeting miR-143 and miR-145.

264The long noncoding RNA H19 modulates cardiac remodeling after infarction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O K Choong ◽  
C Y Chen ◽  
J H Lin ◽  
P J Lin ◽  
J H Zhang ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Noncoding Rna ◽  
Cardiac Fibrosis ◽  
Cardiac Development ◽  
Cardiac Fibroblasts ◽  
Noncoding Rnas ◽  
Interacting Protein ◽  
Functional Studies ◽  
Rna Purification

Abstract Noncoding RNAs account for 80% of human transcripts, but functional studies on noncoding RNAs are relatively few and limited. Long noncoding RNAs (lncRNAs) are known to have an important role in cardiac development, and lately, high-throughput RNA sequencing has been extensively utilized to profile and explore the transcriptome landscape of lncRNAs in failing hearts. These studies have revealed that lncRNAs are mostly dysregulated in failing hearts and their expression signature can discriminate failing hearts of different etiologies. H19 is abundantly expressed in failing human hearts and its polymorphism was shown to possess a significant correlation with the risk of coronary artery diseases. In our study using murine hearts, we discovered that H19 was significantly up regulated in the heart after ischemic injury, with predominant expression in cardiac fibroblasts. This finding piqued our interest to further investigate the function of H19 in the heart. We demonstrated that ectopic overexpression of H19 using the AAV approach led to severe cardiac fibrosis in mouse hearts following myocardial infarction. In light of this finding, we generated H19 knockout mice to further investigate the functionality of H19 and we found that cardiac fibrosis was attenuated in these mice. Altogether, these findings suggested that H19 is a fibrosis regulator during cardiac remodeling process after infarction. Due to the multiple regulatory roles of lncRNAs, we then took advantage of chromatin isolation by RNA purification (ChIRP) to identify the H19-interacting protein, YB-1. Surprisingly, mice with YB-1 knockdown displayed severe cardiac fibrosis even without injury. Furthermore, we demonstrated that YB-1 is a transcriptional suppressor of collagen 1A1. Knockout of H19 in YB-1 knockdown partially suppressed Col1a1 expression, which suggests a negative regulatory role of H19 on YB-1 towards the expression of Col1a1. Taking into account all of these findings, we concluded that H19 mediates collagen expression in fibroblasts through the inhibition of YB-1 activity during cardiac remodeling.

scholarly journals Galectin-3 in Cardiovascular Diseases

2020 ◽  
Vol 21 (23) ◽  
pp. 9232
Author(s):  
Valeria Blanda ◽  
Umberto Marcello Bracale ◽  
Maria Donata Di Taranto ◽  
Giuliana Fortunato
Keyword(s):  
Heart Failure ◽  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Cellular Adhesion ◽  
Cellular Growth ◽  
Cardiac Inflammation ◽  
Galectin 3 ◽  
Diagnostic Applications

Galectin-3 (Gal-3) is a β-galactoside-binding protein belonging to the lectin family with pleiotropic regulatory activities and several physiological cellular functions, such as cellular growth, proliferation, apoptosis, differentiation, cellular adhesion, and tissue repair. Inflammation, tissue fibrosis and angiogenesis are the main processes in which Gal-3 is involved. It is implicated in the pathogenesis of several diseases, including organ fibrosis, chronic inflammation, cancer, atherosclerosis and other cardiovascular diseases (CVDs). This review aims to explore the connections of Gal-3 with cardiovascular diseases since they represent a major cause of morbidity and mortality. We herein discuss the evidence on the pro-inflammatory role of Gal-3 in the atherogenic process as well as the association with plaque features linked to lesion stability. We report the biological role and molecular mechanisms of Gal-3 in other CVDs, highlighting its involvement in the development of cardiac fibrosis and impaired myocardium remodelling, resulting in heart failure and atrial fibrillation. The role of Gal-3 as a prognostic marker of heart failure is described together with possible diagnostic applications to other CVDs. Finally, we report the tentative use of Gal-3 inhibition as a therapeutic approach to prevent cardiac inflammation and fibrosis.

scholarly journals The Role of Epoxyeicosatrienoic Acids in Cardiac Remodeling

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinsheng Lai ◽  
Chen Chen
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Diseases ◽  
Cardiac Remodeling ◽  
Therapeutic Strategy ◽  
Myocardial Hypertrophy ◽  
Epoxyeicosatrienoic Acids ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Related Drug

Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by cytochrome P450 (CYP) epoxygenases, which include four regioisomers: 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET. Each of them possesses beneficial effects against inflammation, fibrosis, and apoptosis, which could combat cardiovascular diseases. Numerous studies have demonstrated that elevation of EETs by overexpression of CYP2J2, inhibition of sEH, or treatment with EET analogs showed protective effects in various cardiovascular diseases, including hypertension, myocardial infarction, and heart failure. As is known to all, cardiac remodeling is the major pathogenesis of cardiovascular diseases. This review will begin with the introduction of EETs and their protective effects in cardiovascular diseases. In the following, the roles of EETs in cardiac remodeling, with a particular emphasis on myocardial hypertrophy, apoptosis, fibrosis, inflammation, and angiogenesis, will be summarized. Finally, it is suggested that upregulation of EETs is a potential therapeutic strategy for cardiovascular diseases. The EET-related drug development against cardiac remodeling is also discussed, including the overexpression of CYP2J2, inhibition of sEH, and the analogs of EET.

scholarly journals Osteopontin: A Promising Therapeutic Target in Cardiac Fibrosis

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1558 ◽  
Author(s):  
Iman Abdelaziz Mohamed ◽  
Alain-Pierre Gadeau ◽  
Anwarul Hasan ◽  
Nabeel Abdulrahman ◽  
Fatima Mraiche
Keyword(s):  
Heart Failure ◽  
Tissue Regeneration ◽  
Cardiac Remodeling ◽  
Therapeutic Target ◽  
Cardiac Fibrosis ◽  
Matricellular Protein ◽  
Physiological Conditions ◽  
Intracellular Signals ◽  
Promising Therapeutic Target

Osteopontin (OPN) is recognized for its significant roles in both physiological and pathological processes. Initially, OPN was recognized as a cytokine with pro-inflammatory actions. More recently, OPN has emerged as a matricellular protein of the extracellular matrix (ECM). OPN is also known to be a substrate for proteolytic cleavage by several proteases that form an integral part of the ECM. In the adult heart under physiological conditions, basal levels of OPN are expressed. Increased expression of OPN has been correlated with the progression of cardiac remodeling and fibrosis to heart failure and the severity of the condition. The intricate process by which OPN mediates its effects include the coordination of intracellular signals necessary for the differentiation of fibroblasts into myofibroblasts, promoting angiogenesis, wound healing, and tissue regeneration. In this review, we discuss the role of OPN in contributing to the development of cardiac fibrosis and its suitability as a therapeutic target.

Endothelial-to-Mesenchymal Transition: Role in Cardiac Fibrosis

2020 ◽  
Vol 26 (1) ◽  
pp. 3-11
Author(s):  
Weijia Cheng ◽  
Xiao Li ◽  
Dongling Liu ◽  
Chaochu Cui ◽  
Xianwei Wang
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiac Fibrosis ◽  
Mesenchymal Cell ◽  
Therapeutic Interventions ◽  
Potential Implication ◽  
Mesenchymal Transition ◽  
Pathological Conditions ◽  
Complex Biological Process ◽  
Endothelial To Mesenchymal Transition

Endothelial-to-mesenchymal transition (EndMT) is a complex biological process by which endothelial cells lose their endothelial cell characteristics and acquire mesenchymal cell properties under certain physiological or pathological conditions. Recently, it has been found that EndMT plays an important role in the occurrence and development of fibrotic cardiovascular diseases. In this review, we first summarize the main induction pathways involved in EndMT process. In addition, we discuss the role of EndMT in fibrotic cardiovascular diseases and its potential implication in new therapeutic interventions.

scholarly journals MicroRNA-150 Inhibits the Activation of Cardiac Fibroblasts by Regulating c-Myb

2016 ◽  
Vol 38 (6) ◽  
pp. 2103-2122 ◽  
Author(s):  
Peng Deng ◽  
Ling Chen ◽  
Zheng Liu ◽  
Ping Ye ◽  
Sihua Wang ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiac Function ◽  
Myocardial Fibrosis ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Pressure Overload ◽  
Heart Cell ◽  
Factor C

Background/Aims: Cardiac fibrosis is the primary cause of deteriorated cardiac function in various cardiovascular diseases. Numerous studies have demonstrated that microRNAs (miRNAs) are critical regulators of myocardial fibrosis. Specifically, many studies have reported that miR-150 is downregulated in cardiovascular diseases, such as acute myocardial infarction (AMI), myocardial hypertrophy and myocardial fibrosis. However, the exact role of miR-150 in these pathological processes remains unknown. Methods: We used the transverse aortic constriction (TAC) mouse model to study the role of miR-150 in cardiac fibrosis induced by pressure overload. After the TAC operation, qRT-PCR was used to measure the expression profiles of miR-150 in left ventricle tissues and populations of primary heart cell types. Then, we used both miR-150 knockout mice and wild type (WT) mice in the TAC model. Changes in cardiac function and pathology were measured using transthoracic echocardiography and pathological analysis, respectively. Furthermore, we predicted the target of miR-150 in cardiac fibroblasts (CFs) and completed in vitro CF transfection experiments using miR-150 analogs and siRNA corresponding to the predicted target. Results: We observed decreased expression levels of miR-150 in hearts suffering pressure overload, and these levels decreased more sharply in CFs than in cardiomyocytes. In addition, the degrees of cardiac function deterioration and cardiac fibrosis in miR-150-/- mice were more severe than were those in WT mice. By transfecting CFs with an miR-150 analog in vitro, we observed that miR-150 inhibited cardiac fibroblast activation. We predicted that the transcription factor c-Myb was the target of miR-150 in CFs. Transfecting CFs with c-Myb siRNA eliminated the effects of an miR-150 inhibitor, which promoted CF activation. Conclusion: These findings reveal that miR-150 acts as a pivotal regulator of pressure overload-induced cardiac fibrosis by regulating c-Myb.

scholarly journals Role of serum interleukin-6 in heart failure

2018 ◽  
Vol 5 (4) ◽  
pp. 936 ◽  
Author(s):  
Smita Amol Deokar ◽  
Sucheta P. Dandekar ◽  
Ganesh A. Shinde ◽  
Surekha S. Prabhu ◽  
Mugdha Patawardhan
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Interleukin 6 ◽  
Inflammatory Marker ◽  
Serum Analysis ◽  
Heart Failure Patients ◽  
Growing Body ◽  
Age And Sex

Background: A growing body of evidence suggests that inflammation plays the key role in different cardiovascular diseases. But very study has been done so far in relation to serum interleukin-6 in heart failure patients.  The aim of the study was to measure serum interleukin-6 in heart failure patients.Methods: Total 22 heart failure patients and 22 age and sex matched controls were included in this study from August 2015 to June 2016 for serum analysis of interleukin-6.Results: serum interleukin-6 was significantly [median(IQR) 14.3(26.2) pg/mL] increased in heart failure patients compared to age and sex matched controls [median(IQR) 0(2.4) pg/mL].Conclusions: Even though little is known about function of interleukin-6 in heart failure patients, this study shows that increased level of IL-6 in heart failure patients plays an important role as a pro-inflammatory marker in development of cardiovascular disease i.e. heart failure.

scholarly journals Protective role of berberine in isoprenaline-induced cardiac fibrosis in rats

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yan Che ◽  
Di-Fei Shen ◽  
Zhao-Peng Wang ◽  
Ya-Ge Jin ◽  
Qing-Qing Wu ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
In Vitro Study ◽  
Protective Role ◽  
Vitro Study ◽  
Macrophage Infiltration ◽  
Control Group ◽  
Tgf Β1

Abstract Background Cardiac fibrosis is a crucial aspect of cardiac remodeling that can severely affect cardiac function. Cardiac fibroblasts surely influence this process. Besides, macrophage plays an essential role in cardiac remodeling after heart injury. However, whether macrophage influence fibroblasts remain a question worth exploring. This study aimed to define the role of berberine (BBR) on isoprenaline (ISO)-induced cardiac fibrosis in an in vivo rat model and try to figure out the mechanism in vitro study. Methods The Sprague-Dawley rats were divided into five groups: control group, ISO-treated group, and ISO + BBR (10 mg/kg/d, 30 mg/kg/d, and 60 mg/kg/d orally)-pretreatment groups. Fibrosis was induced by ISO administration (5 mg/kg/d subcutaneously) for 10 days. One day after the last injection, all of the rats were sacrificed. Using picrosirius red (PSR) straining, immunohistochemistry, immunofluorescence, flow cytometry, western blot, RT-qPCR and cell co-culture, we explored the influence of pretreatment by BBR on ISO-induced cardiac fibrosis. Results Our results showed that BBR pretreatment greatly limited ISO-induced cardiac fibrosis and dysfunction. Moreover, BBR administration reduced macrophage infiltration into the myocardium of ISO-treated rats and inhibited transforming growth factor (TGF)-β1/smads signaling pathways in comparison to that seen in the ISO group. Besides, in vitro study showed that BBR-pretreatment reduced ISO-induced TGF-β1 mRNA expression in macrophages and ISO stimulation of macrophages significantly increased the expression of fibrotic markers in fibroblasts, but BBR-pretreatment blocked this increase. Conclusion Our results showed that BBR may have a protective role to cardiac injury via reducing of macrophage infiltration and forbidding fibroblasts transdifferent into an ‘activated’ secretory phenotype, myofibroblasts.

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