scholarly journals Methyl Ferulic Acid Attenuates Human Cardiac Fibroblasts Differentiation and Myocardial Fibrosis by Suppressing pRB-E2F1/CCNE2 and RhoA/ROCK2 Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Rongheng Liao ◽  
Zhen Qi ◽  
Ri Tang ◽  
Renrong Wang ◽  
Yongyi Wang
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Ferulic Acid ◽  
Myocardial Fibrosis ◽  
Cardiac Fibroblasts ◽  
Treated Group ◽  
Biologically Active ◽  
Human Cardiac Fibroblasts ◽  
Related Proteins

Background: Myocardial fibrosis is a key pathological process after myocardial infarction, which leads to poor outcomes in patients at the end stage. Effective treatments for improving prognosis of myocardial fibrosis are needed to be further developed. Methyl ferulic acid (MFA), a biologically active monomer extracted and purified from the Chinese herbal medicine, is reported as an attenuator in many diseases. In this study, we aim to reveal the role it plays in myocardial fibrosis after myocardial infarction and its possible mechanism.Results: Firstly, we found that MFA attenuated the expression of fibrosis-related proteins and the ability of migration and proliferation in TGF-β1–induced human cardiac fibroblasts (HCFs). Then, myocardial fibrosis after myocardial infarction models on mouse was built to reveal the in vivo affection of MFA. After 28 days of treatments, fibrosis areas, cardiac function, and expression of fibrosis-related proteins were all improved in the MFA-treated group than the myocardial infarction group. Finally, to elucidate the mechanism of phenomenon we observed, we found that MFA attenuated HCF differentiation after myocardial infarction by suppressing the migration and proliferation in HCFs, which was by suppressing the pRB-E2F1/CCNE2 and the RhoA/ROCK2 pathway.Conclusion: Our findings showed that MFA attenuated the expression of fibrosis-related proteins, and the ability of migration and proliferation in HCFs improved the cardiac function of myocardial infarction mice; meanwhile, the mechanism of that was by suppressing the pRB-E2F1/CCNE2 and the RhoA/ROCK2 pathway.

scholarly journals Myocardial fibrosis reversion via rhACE2-electrospun fibrous patch for ventricular remodeling prevention

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zeping Qiu ◽  
Jingwen Zhao ◽  
Fanyi Huang ◽  
Luhan Bao ◽  
Yanjia Chen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Fibrosis ◽  
Ventricular Remodeling ◽  
Cardiac Fibroblasts ◽  
Cost Effective ◽  
Intramyocardial Injection ◽  
Undesirable Consequence ◽  
Adverse Remodeling

AbstractMyocardial fibrosis and ventricular remodeling were the key pathology factors causing undesirable consequence after myocardial infarction. However, an efficient therapeutic method remains unclear, partly due to difficulty in continuously preventing neurohormonal overactivation and potential disadvantages of cell therapy for clinical practice. In this study, a rhACE2-electrospun fibrous patch with sustained releasing of rhACE2 to shape an induction transformation niche in situ was introduced, through micro-sol electrospinning technologies. A durable releasing pattern of rhACE2 encapsulated in hyaluronic acid (HA)—poly(L-lactic acid) (PLLA) core-shell structure was observed. By multiple in vitro studies, the rhACE2 patch demonstrated effectiveness in reducing cardiomyocytes apoptosis under hypoxia stress and inhibiting cardiac fibroblasts proliferation, which gave evidence for its in vivo efficacy. For striking mice myocardial infarction experiments, a successful prevention of adverse ventricular remodeling has been demonstrated, reflecting by improved ejection fraction, normal ventricle structure and less fibrosis. The rhACE2 patch niche showed clear superiority in long term function and structure preservation after ischemia compared with intramyocardial injection. Thus, the micro-sol electrospun rhACE2 fibrous patch niche was proved to be efficient, cost-effective and easy-to-use in preventing ventricular adverse remodeling.

scholarly journals Lcz696 Alleviates Myocardial Fibrosis After Myocardial Infarction Through the sFRP-1/Wnt/β-Catenin Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Liu ◽  
Xuehui Zheng ◽  
Chen Zhang ◽  
Chunmei Zhang ◽  
Peili Bu
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Signaling Pathway ◽  
Myocardial Fibrosis ◽  
Cardiac Fibrosis ◽  
Corn Oil ◽  
Inhibitory Effect ◽  
Neprilysin Inhibitor ◽  
Angiotensin Receptor Neprilysin Inhibitor ◽  
Related Proteins

Background: Lcz696 (ARNI, angiotensin receptor–neprilysin inhibitor; sacubitril/valsartan) shows an inhibitory effect on fibrosis after myocardial infarction (MI). However, the underlying signaling mechanisms are poorly understood. The Wnt/β-catenin signaling pathway is activated after MI and participates in the process of myocardial fibrosis. Here, we aimed to assess the efficacy of ARNI for alleviating myocardial fibrosis after MI and hypothesized that ARNI alleviates myocardial fibrosis by inhibiting the Wnt/β-catenin signaling pathway and overexpressing sFRP-1, an inhibitor of the Wnt/β-catenin signaling pathway.Methods: Mice randomized at 1 week post-MI were administered lcz696 (60 mg/kg, n = 21), valsartan (30 mg/kg, n = 19), or corn oil (n = 13) orally for 4 weeks, while the sham-operated group received vehicle (corn oil, n = 19). Cardiac function and extent of myocardial fibrosis were measured. Western blotting and quantitative real-time polymerase chain reaction were used to detect the expression of Wnt/β-catenin pathway-related proteins. Furthermore, primary myocardial fibroblasts were stimulated with angiotensin II (Ang II) and cultured with lcz696 and the sFRP-1 inhibitor way316606 to detect the expression of Wnt/β-catenin pathway proteins.Results: Both lcz696 and valsartan alleviated myocardial fibrosis and improved cardiac function, but lcz696 had superior efficiency compared to valsartan. Furthermore, β-catenin expression was inhibited and sFRP-1 was overexpressed after drug treatment, which could be significantly improved by lcz696 in mice. In addition, lcz696 inhibited β-catenin expression in AngII-stimulated myocardial fibroblasts, and β-catenin expression increased after the inhibition of sFRP-1.Conclusion: ARNI alleviated cardiac fibrosis and cardiac remodeling by inhibiting the Wnt/β-catenin signaling pathway. In addition, ARNI can lead to overexpression of sFRP-1, which is an inhibitor of the Wnt/β-catenin signaling pathway. These results indicate a new therapeutic target of ARNI to improve myocardial fibrosis and prevent myocardial remodeling.

Abstract 595: Blocking Cadherin-11 Adhesion After Myocardial Infarction Preserves Cardiac Function

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Alison Schroer ◽  
W. David Merryman
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Treated Group ◽  
Blocking Antibody ◽  
Infarct Healing ◽  
Functional Blocking ◽  
New Treatment ◽  
Ventricle Volume

Introduction: Over one million Americans experience myocardial infarction (MI) every year, and the resulting scar and subsequent cardiac fibrosis contribute to heart failure and death. The cells primarily responsible for scar formation and cardiac fibrosis are cardiac fibroblasts (CFs), which differentiate into active myofibroblasts in response to injury, expressing a specialized adhesion protein: cadherin-11 (CDH11). CDH11 has recently been shown to contribute to inflammation and fibrosis in both rheumatoid arthritis and pulmonary fibrosis; therefore we hypothesized that blocking CDH11 adhesion after MI would reduce inflammation-driven infarct expansion and fibrotic remodeling to improve functional outcomes in mice. Methods: MI was induced in mice by ligation of a coronary artery, and mice were injected with a functional blocking antibody against CDH11 or a control IgG for 21 days. We assessed dynamic cardiac function with echocardiogram and measured changes in protein transcription and expression by qPCR and western blot. Results and discussion: Our preliminary results reveal an increase in both survival and cardiac function (ejection fraction) in the treated group relative to controls (A-B). Furthermore, increasing dilation of the left ventricle observed in the control was curtailed in the animals receiving the blocking antibody, resulting in significantly reduced total ventricle volume at 21 days post-MI (C-D). This reduced remodeling was preceded by reduced transcription of IL-6, a pro-inflammatory cytokine, in the antibody treated group three days post-MI (E). Our findings suggest that targeting CDH11-expressing myofibroblasts limits inflammation-driven remodeling while preserving cardiac function. The completion of this project will fully characterize phenotypic changes and tissue remodeling throughout the course of infarct healing, providing new biological insights, and highlighting a potential new treatment strategy for MI.

scholarly journals Salvia miltiorrhizaandCarthamus tinctoriusExtract Prevents Cardiac Fibrosis and Dysfunction after Myocardial Infarction by Epigenetically Inhibiting Smad3 Expression

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jing Yang ◽  
Bo Wang ◽  
Na Li ◽  
Qingqing Zhou ◽  
Wenhui Zhou ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Growth Factor ◽  
Cardiac Function ◽  
Myocardial Fibrosis ◽  
Histone Methylation ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Salvia Miltiorrhiza ◽  
Left Ventricular

The incidence of cardiac dysfunction after myocardial infarction (MI) continues to increase despite advances in treatment. Excessive myocardial fibrosis plays a vital role in the development of adverse cardiac remodeling and deterioration of cardiac function. Understanding the molecular and cellular mechanism of the fibrosis process and developing effective therapeutics are of great importance.Salvia miltiorrhizaandCarthamus tinctoriusextract (SCE) is indicated for angina pectoris and other ischemic cardiovascular diseases in China. SCE has been shown to inhibit the platelet activation and aggregation, ameliorate ROS-induced myocardial necrosis by inhibiting mitochondrial permeability transition pore opening, and promote angiogenesis by upregulating the expression of vascular endothelial growth factor (VEGF). However, whether SCE has effect on cardiac fibrosis after MI is not fully clear. Here, a mouse model of MI was established to observe the effect of SCE upon survival, cardiac function, myocardial fibrosis, and inflammation. Quantitative PCR and western blot assays were used to determine the expression of genes related to transforming growth factor-β(TGF-β) cascade and inflammatory responsesin vivo. Additionally, the effects of SCE upon the collagen production, TGF-β/Smad3 (SMAD family member 3) signaling, and the levels of histone methylation in primary cardiac fibroblasts were detected. We found that SCE treatment significantly improved survival and left ventricular function in mice after MI. Inhibition of inflammation and fibrosis, as well as decreased expression of Smad3, was observed with SCE treatment. In TGF-β-stimulated cardiac fibroblasts, SCE significantly decreased the expression of collagen,α-smooth muscle actin (α-SMA), and Smad3. Furthermore, SCE treatment downregulated the levels of H3K4 trimethylation (H3K4me3) and H3K36 trimethylation (H3K36me3) at theSmad3promoter region of cardiac fibroblasts, leading to inhibition ofSmad3transcription. Our findings suggested that SCE prevents myocardial fibrosis and adverse remodeling after MI with a novel mechanism of suppressing histone methylation of theSmad3promoter and its transcription.

scholarly journals Manuscript title Microparticles Containing MiR-625-5p In Coronary Artery Reduce Myocardial Fibrosis After Myocardial Infarction

2021 ◽  
Author(s):  
Ningxin Wen ◽  
Qi Zhang ◽  
Xuan Wu ◽  
Jianing Gao ◽  
Yangkai Xu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Myocardial Fibrosis ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
High Mobility ◽  
Coronary Intervention ◽  
Thrombus Aspiration ◽  
St Segment Elevation ◽  
Emergency Percutaneous Coronary Intervention

Abstract PurposeBlood from infarct-related arteries obtained by thrombus aspiration is good material for studying the local microenvironment of blood vessels in myocardial infarction. Here, we aimed to observe the effects of intracoronary microparticles (MPs) on cardiac fibrosis and to find associated microRNAs in MPs.MethodsBlood samples were collected from patients with ST-segment elevation myocardial infarction who underwent emergency percutaneous coronary intervention, and sub-supersonic centrifugation was used to separate the MPs.ResultsWe found that rats treated with intracoronary MPs showed better cardiac function after myocardial infarction compared with rats treated with PBS control or peripheral MPs. RNA microarray analysis indicated that microRNAs, especially miR-625-5p, may play a role in the process. Supplementation with miR-625-5p inhibited proliferation of cardiac fibroblasts and myocardial fibrosis in a mouse myocardial infarction model. ConclusionOur findings indicate that plasma MPs in infarct-related arteries in patients with acute myocardial infarction can inhibit myocardial fibrosis and improve cardiac function, with a process mediated by miR-625-5p and HMGA1 (high mobility group AT-hook 1). The current study may provide a possible reference for thrombus aspiration standard.

scholarly journals Author Correction: In vivo transduction of ETV2 improves cardiac function and induces vascular regeneration following myocardial infarction

2019 ◽  
Vol 51 (9) ◽  
pp. 1-1 ◽  
Author(s):  
Sunghun Lee ◽  
Dong Hun Lee ◽  
Bong-Woo Park ◽  
Ri Youn Kim ◽  
Anh Duc Hoang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Vascular Regeneration

scholarly journals Knockdown of MicroRNA-1 in the Hippocampus Ameliorates Myocardial Infarction Induced Impairment of Long-Term Potentiation

2018 ◽  
Vol 50 (4) ◽  
pp. 1601-1616 ◽  
Author(s):  
Ji-Chao Ma ◽  
Ming-Jing Duan ◽  
Ke-Xin Li ◽  
Das Biddyut ◽  
Shuai Zhang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Sham Group ◽  
Long Term Potentiation ◽  
Stimulus Response ◽  
Protein Levels ◽  
Term Potentiation ◽  
Passive And Active Avoidance ◽  
Related Proteins

Backgrounds/Aims: It has been reported that myocardial infarction (MI) is a risk factor for vascular dementia. However, the molecular mechanism remains largely unknown. Methods: MI mice were generated by ligation of the left coronary artery (LCA) for 4 weeks. Passive and active avoidance tests were performed to evaluate the cognitive ability of MI mice. A theta-burst stimulation (TBS) protocol was applied to elicit long-term potentiation (LTP) of the perforant pathway-dentate gyrus synapse (PP-DG). Western blot analysis was employed to assess protein levels. Results: In this study, we demonstrated that after 4 weeks of MI, C57BL/6 mice had significantly impaired memory. Compared with the sham group, in vivo physiological recording in the MI group revealed significantly decreased amplitude of population spikes (PS) with no effect on the latency and duration of the stimulus-response curve. The amplitude of LTP was markedly decreased in the MI group compared with the sham group. Further examination showed that the expression of the TBS-LTP-related proteins BDNF, GluA1 and phosphorylated GluA1 were all decreased in the MI group compared with those in the sham group. Strikingly, all these changes were prevented by hippocampal stereotaxic injection of an anti-miR-1 oligonucleotide fragment carried by a lentivirus vector (lenti-pre-AMO-1). Conclusion: MI induced cognitive decline and TBS-LTP impairment, and decreased BDNF and GluA1 phosphorylation levels from overexpression of miR-1ated were involved in this process.

scholarly journals Garcinoic Acid Improves Cardiac Function and Enhances Angiogenesis Following Myocardial Infarction

2021 ◽  
Author(s):  
Hongyao Hu ◽  
Wei Li ◽  
Yanzhao Wei ◽  
Hui Zhao ◽  
Zhenzhong Wu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Ventricular Remodeling ◽  
Vehicle Group ◽  
Potential Mechanism ◽  
Garcinia Kola ◽  
Angiogenic Proteins

Abstract Cardiac ischemia impairs angiogenesis in response to hypoxia, resulting in ventricular remodeling. Garcinoic acid (GA), the extraction from the plant garcinia kola, is validated to attenuate inflammatory response. However, the role of GA in heart failure (HF) and neovascularization after myocardial infarction (MI) is incompletely understood. The present study is striving to explore the role of GA and the potential mechanism of which in cardiac function after MI. SD rats were randomized into sham group, MI+vehicle group, and MI+GA group in vivo. Human umbilical endothelial cells (HUVECs) were cultured in vehicle or GA, and then additionally exposed to 2% hypoxia environment in vitro. MI rats displayed a dramatically reduced myocardial injury, cardiac function and vessel density in the peri-infarcted areas. GA delivery markedly improved cardiac performance and promoted angiogenesis. In addition, GA significantly enhanced tube formation in HUVECs under hypoxia condition. Furthermore, the expressions of pro-angiogenic factors HIF-1α, VEGF-A and bFGF, and pro-angiogenic proteins phospho-VEGFR2Tyr1175 and VEGFR2, as well as phosphorylation levels of Akt and eNOS were increased by GA treatment. In conclusion, GA preserved cardiac function after MI probably via promoting neovascularization. And the potential mechanism may be partially through upregulating the expressions of HIF-1α, VEGF-A, bFGF, phospho-VEGFR2Tyr1175 and VEGFR2 and activating the phosphorylations of Akt and eNOS.

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