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Deep phenotyping of miRNAs in exercise-induced cardiac hypertrophy and fibrosis

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Abstract

Cardiac hypertrophy (CH) is an adaptational enlargement of the myocardium, in exposure to altered stress conditions or in case of injury which can lead to heart failure and death. MicroRNAs (miRNAs) are non-coding RNAs that play a significant role in modulating gene expression. Here, we aimed to identify new miRNAs effective in an experimental CH model and to find an epigenetic biomarker that could demonstrate therapeutic targets responsible for the pathology of heart tissue and serum. In this study, Sprague–Dawley male rats were divided into the training group (TG, n=9) and the control group (CG, n=6). Systolic and diastolic dimensions of the left ventricle and myocardial wall thickness were measured by echocardiography to assess CH. After the exercise program of the rats, miRNA expression measurements and histological analyses were performed. The 25,000 genes in the rat genome were searched using microarray analysis. A total of 128 miRNAs were selected according to the fold change rates, and nine miRNAs were validated for expression analysis. The terminal deoxynucleotidyl transferase dUTP nick (TUNEL) method was used to detect apoptotic cells. Cell proliferation was evaluated by the proliferative cell nuclear antigen (PCNA) method. Necrosis, bleeding, and intercellular edema were detected in TG. The mean histopathological score was higher in TG (p=0.03). There were rarely positive cells for apoptosis of both groups in cardiomyocytes. In the receiver characteristic curve analysis (ROC), the heart tissue rno-miR-290 had an area under the curve (AUC) of 0.920 with 100% sensitivity and 89.90% specificity (p=0.045), rno-miR-194-5p had AUC of 0.940 with 83.33% sensitivity and 100% specificity (p=0.003), and the serum rno-miR-132-3p AUC was 0.880 with 66.67% sensitivity and 100% specificity (p=0.004) in TG. miR-194-5p was used as a therapeutic target for remodeling the cardiac process. While miR-290 contributes to CH as a negative regulator, miR-132 in serum is effective in the pathological and physiological cardiac remodeling process and is a candidate biomarker.

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Funding

This work was supported by the Scientific Research Projects Unit of Istanbul University (Project No.: 48783).

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Authors and Affiliations

  1. Department of Physiology, Medical Faculty, Malatya Turgut Ozal University, Malatya, Turkey

    Mukaddes Pala

  2. Department of Nutrition and Dietetics, Health Science Faculty, Gaziantep University, Gaziantep, Turkey

    Senay Gorucu Yilmaz

  3. Department of Physiology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey

    Mehmet Altan & Osman Fuat Sonmez

  4. Department of Sports Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey

    Sensu Dincer & Gokhan Metin

  5. Department of Physiology, Medical Faculty, Namık Kemal University, Tekirdag, Turkey

    Murat Mengi

  6. Department of Immunology, Hamidiye Health Science Institute, Health Science University, Istanbul, Turkey

    Aydin Karabulut

  7. Department of Pathology, Medical Faculty, Malatya Turgut Ozal University, Malatya, Turkey

    Fahriye Secil Tecellioglu

  8. Department of Medical Biology, Medical Faculty, Bezmialem Vakif University, Istanbul, Turkey

    Fahri Akbas

  9. Institute of Cardiology, Istanbul University, Istanbul, Turkey

    Mustafa Yildiz

  10. Department of Histology and Embryology, Veterinary Faculty, Dokuz Eylul University, Izmir, Turkey

    Meltem Kumas Kulualp

  11. Department of Histology and Embryology, Medical Faculty, Bezmialem Vakif University, Istanbul, Turkey

    Mukaddes Esrefoglu

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  1. Mukaddes Pala
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  2. Senay Gorucu Yilmaz
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  12. Mukaddes Esrefoglu
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Correspondence to Mukaddes Pala.

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Corresponding editor: Sreenivas Chavali

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Pala, M., Gorucu Yilmaz, S., Altan, M. et al. Deep phenotyping of miRNAs in exercise-induced cardiac hypertrophy and fibrosis. J Biosci 48, 36 (2023). https://doi.org/10.1007/s12038-023-00360-4

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