0
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Breviscapine Pretreatment Inhibits Myocardial Inflammation and Apoptosis in Rats After Coronary Microembolization by Activating the PI3K/Akt/GSK-3β Signaling Pathway

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose

          Coronary microembolization (CME) can cause myocardial inflammation, apoptosis and progressive cardiac dysfunction. On the other hand, breviscapine exerts a significant cardioprotective effect in many cardiac diseases although its role and the potential mechanisms in CME remain unclear. Therefore, the present study aimed to ascertain whether pretreatment with breviscapine could improve CME-induced myocardial injury by alleviating myocardial inflammation and apoptosis. The possible underlying mechanisms were also explored.

          Methods

          In this study, 48 Sprague-Dawley (SD) rats were randomly assigned to the CME, CME + breviscapine (CME + BE), CME + breviscapine + LY294002 (CME + BE + LY) and sham groups (12 rats per group). In addition, the CME model was successfully established by injecting 42 μm inert plastic microspheres into the left ventricle of rats. Rats in the CME + BE and CME + BE + LY groups received 40 mg/kg/d of breviscapine for 7 days before inducing CME. Moreover, rats in the CME + BE + LY group were intraperitoneally injected with the phosphoinositide 3-kinase (PI3K) specific inhibitor, LY294002 (10 mg/kg) 30 minutes before CME modeling. 12 h after surgery, the study measured cardiac function, the serum levels of markers of myocardial injury, myocardial inflammation-associated mRNAs and proteins, myocardial apoptosis-associated mRNAs and proteins and conducted myocardial histopathology.

          Results

          The findings demonstrated that pretreatment with breviscapine alleviated myocardial injury following CME by improving cardiac dysfunction, decreasing the serum levels of markers of myocardial injury, reducing the size of myocardial microinfarct and lowering the cardiomyocyte apoptotic index. More importantly, pretreatment with breviscapine resulted to a decrease in the levels of inflammatory and pro-apoptotic mRNAs and proteins in myocardial tissues and there was an increase in the levels of anti-apoptotic mRNAs and proteins. However, these protective effects were eliminated when breviscapine was combined with LY294002.

          Conclusion

          The findings from this study indicated that breviscapine may inhibit myocardial inflammation and apoptosis by regulating the PI3K/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway, thereby ameliorating CME-induced cardiac dysfunction and reducing myocardial injury.

          Related collections

          Most cited references 41

          • Record: found
          • Abstract: not found
          • Article: not found

          Coronary microembolization and microvascular dysfunction

            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Therapeutic Effects of Breviscapine in Cardiovascular Diseases: A Review

            Breviscapine is a crude extract of several flavonoids of Erigeron breviscapus (Vant.) Hand.-Mazz., containing more than 85% of scutellarin, which has been traditionally used in China as an activating blood circulation medicine to improve cerebral blood supply. Accumulating evidence from various in vivo and in vitro studies has shown that breviscapine exerts a broad range of cardiovascular pharmacological effects, including vasodilation, protection against ischaemia/reperfusion (I/R), anti-inflammation, anticoagulation, antithrombosis, endothelial protection, myocardial protection, reduction of smooth muscle cell migration and proliferation, anticardiac remodeling, antiarrhythmia, blood lipid reduction, and improvement of erectile dysfunction. In addition, several clinical studies have reported that breviscapine could be used in conjunction with Western medicine for cardiovascular diseases (CVDs) including coronary heart disease, myocardial infarction, hypertension, atrial fibrillation, hyperlipidaemia, viral myocarditis, chronic heart failure, and pulmonary heart disease. However, the protective effects of breviscapine on CVDs based on experimental studies along with its underlying mechanisms have not been reviewed systematically. This paper reviewed the underlying pharmacological mechanisms in the cardioprotective effects of breviscapine and elucidated its clinical applications.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Perfusion-contraction mismatch with coronary microvascular obstruction: role of inflammation.

              A close relationship exists between regional myocardial blood flow (RMBF) and function during acute coronary inflow restriction (perfusion-contraction matching). However, the relationship of flow and function during coronary microvascular obstruction is unknown. In 12 anesthetized dogs, the left circumflex coronary artery was perfused from an extracorporeal circuit. After control measurements, 3,000 microspheres (42 micrometer diameter) per milliliter per minute inflow were injected to cause a microembolism (ME, n = 6). With unchanged systemic hemodynamics and RMBF, posterior systolic wall thickening (PWT) decreased from 19.8 +/- 1.9% SD at control to 13.3 +/- 4.0, 10.3 +/- 3.8, and 6.9 +/- 4.7% (P < 0.05 vs. control) at 1, 4, and 8 h, respectively. For comparison, inflow was progressively reduced to match PWT to that of the ME group at 1, 4, and 8 h (stenosis, STE, n = 6). RMBF in the STE group was reduced in proportion to PWT. Infarct size was not different among groups (6.5 +/- 4.5 vs. 3.4 +/- 3.2%). However, the number of leukocytes infiltrating the area at risk was significantly greater in the ME group than in the STE group. Coronary microembolization results in perfusion-contraction mismatch and is associated with an inflammatory response.
                Bookmark

                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                25 February 2021
                2021
                : 15
                : 843-855
                Affiliations
                [1 ]Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases , Nanning, People’s Republic of China
                [2 ]Department of Emergency, The First Affiliated Hospital of Guangxi Medical University , Nanning, People’s Republic of China
                Author notes
                Correspondence: Lang Li Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases , 6 Shuangyong Road, Nanning, 530021, Guangxi, People’s Republic of ChinaTel/Fax +86-771-5331171 Email drlilang99@126.com
                Article
                293382
                10.2147/DDDT.S293382
                7920514
                33658766
                © 2021 Chen et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 7, Tables: 2, References: 41, Pages: 13
                Categories
                Original Research

                Comments

                Comment on this article