3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      miR-3574 ameliorates intermittent hypoxia-induced cardiomyocyte injury through inhibiting Axin1

      research-article

      Read this article at

      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

          Objective: miRNAs play critical roles in the regulation of many cardiovascular diseases. However, its role and potential mechanism in cardiac injury caused by obstructive sleep apnea (OSA) remain poorly elucidated. In the present study, we aimed to investigate the effects of miR-3574 on cardiomyocyte injury under intermittent hypoxia (IH).

          Results: We confirmed that IH inhibited cell viability, induced cell apoptosis and suppressed miR-3574 expression in the H9c2. miR-3574 overexpression could ameliorate the effects of IH on the cell viability and cell apoptosis in the H9c2. Axin1 was a target gene of miR-3574, and miR-3574 overexpression reduced the expression of Axin1. miR-3574 could inhibit the IH-induced cardiomyocyte injury via downregulating Axin1. However, Axin1 could partially reverse these effects of miR-3574.

          Conclusion: Our study first reveals that miR-3574 could alleviate IH-induced cardiomyocyte injury by targeting Axin1, which may function as a novel and promising therapy target for OSA-associated cardiovascular diseases.

          Methods: H9c2 were exposed to IH condition. CCK-8 assay was applied to determine cell viability of H9c2. qRT-PCR was conducted to measure the expression level of mRNA and miRNA. Western blot assay was then performed to detect the protein levels. Finally, we used dual-luciferase reporter assay identify the potential target of miR-3574.

          Related collections

          Most cited references36

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

          miRNAS in cardiovascular diseases: potential biomarkers, therapeutic targets and challenges

          Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in the world. Although considerable progress has been made in the diagnosis, treatment and prognosis of CVD, there is still a critical need for novel diagnostic biomarkers and new therapeutic interventions to decrease the incidence of this disease. Recently, there is increasing evidence that circulating miRNAs (miRNAs), i.e. endogenous, stable, single-stranded, short, non-coding RNAs, can be used as diagnostic biomarkers for CVD. Furthermore, miRNAs represent potential novel therapeutic targets for several cardiovascular disorders. In this review we provides an overview of the effects of several CVD; including heart failure, acute myocardial infarction, arrhythmias and pulmonary hypertension; on levels of circulating miRNAs. In addition, the use of miRNA as therapeutic targets is also discussed, as well as challenges and recommendations in their use in the diagnosis of CVD.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction

            The primary cause of heart failure is the loss of cardiomyocytes in the diseased adult heart. Previously, we reported that the miR-17-92 cluster plays a key role in cardiomyocyte proliferation. Here, we report that expression of miR-19a/19b, members of the miR-17-92 cluster, is induced in heart failure patients. We show that intra-cardiac injection of miR-19a/19b mimics enhances cardiomyocyte proliferation and stimulates cardiac regeneration in response to myocardial infarction (MI) injury. miR-19a/19b protected the adult heart in two distinctive phases: an early phase immediately after MI and long-term protection. Genome-wide transcriptome analysis demonstrates that genes related to the immune response are repressed by miR-19a/19b. Using an adeno-associated virus approach, we validate that miR-19a/19b reduces MI-induced cardiac damage and protects cardiac function. Finally, we confirm the therapeutic potential of miR-19a/19b in protecting cardiac function by systemically delivering miR-19a/19b into mice post-MI. Our study establishes miR-19a/19b as potential therapeutic targets to treat heart failure.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Preclinical development of a miR-132 inhibitor for heart failure treatment

              Despite proven efficacy of pharmacotherapies targeting primarily global neurohormonal dysregulation, heart failure (HF) is a growing pandemic with increasing burden. Treatments mechanistically focusing at the cardiomyocyte level are lacking. MicroRNAs (miRNA) are transcriptional regulators and essential drivers of disease progression. We previously demonstrated that miR-132 is both necessary and sufficient to drive the pathological cardiomyocytes growth, a hallmark of adverse cardiac remodelling. Therefore, miR-132 may serve as a target for HF therapy. Here we report further mechanistic insight of the mode of action and translational evidence for an optimized, synthetic locked nucleic acid antisense oligonucleotide inhibitor (antimiR-132). We reveal the compound’s therapeutic efficacy in various models, including a clinically highly relevant pig model of HF. We demonstrate favourable pharmacokinetics, safety, tolerability, dose-dependent PK/PD relationships and high clinical potential for the antimiR-132 treatment scheme.
                Bookmark

                Author and article information

                Journal
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                31 March 2021
                11 February 2021
                : 13
                : 6
                : 8068-8077
                Affiliations
                [1 ]Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Fujian Medical University, Fengze, Quanzhou 362000, China
                [2 ]Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Taijiang, Fuzhou 350005, China
                [3 ]The First Affiliated Hospital of Xiamen University, Siming, Xiamen 361001, China
                [4 ]The Second Affiliated Hospital of Fujian Medical University, Fengze, Quanzhou 362000, China
                Author notes
                [*]

                Equal contribution

                Correspondence to: Qichang Lin; email: change4@fjmu.edu.cn
                Article
                202480 202480
                10.18632/aging.202480
                8034950
                33582657
                43337437-d4d7-42d4-9596-57c1b1df8ca8
                Copyright: © 2021 Chen et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 August 2020
                : 31 October 2020
                Categories
                Research Paper

                Cell biology
                mir-3574,obstructive sleep apnea,axin1,intermittent hypoxia,cardiomyocyte injury
                Cell biology
                mir-3574, obstructive sleep apnea, axin1, intermittent hypoxia, cardiomyocyte injury

                Comments

                Comment on this article