Pachymic Acid Attenuated Doxorubicin-Induced Heart Failure by Suppressing miR-24 and Preserving Cardiac Junctophilin-2 in Rats
| Autor: | Alaa Elsayed Salama, Nahla N Younis, Rana G. Eissa, Mohamed A. Shaheen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
losartan
QH301-705.5 E–C coupling heart failure Cardiomegaly Pharmacology Ryanodine receptor 2 doxorubicin Article Catalysis Inorganic Chemistry Contractility medicine Adjuvant therapy Animals Myocytes Cardiac Doxorubicin Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy pachymic acid Ryanodine receptor business.industry Organic Chemistry Membrane Proteins Ryanodine Receptor Calcium Release Channel General Medicine medicine.disease Triterpenes Rats Computer Science Applications Disease Models Animal MicroRNAs Chemistry medicine.anatomical_structure Losartan Gene Expression Regulation Ventricle Heart failure Heart Function Tests ryanodine receptors Disease Susceptibility business Signal Transduction medicine.drug |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 10710, p 10710 (2021) International Journal of Molecular Sciences Volume 22 Issue 19 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Defects in cardiac contractility and heart failure (HF) are common following doxorubicin (DOX) administration. Different miRs play a role in HF, and their targeting was suggested as a promising therapy. We aimed to target miR-24, a suppressor upstream of junctophilin-2 (JP-2), which is required to affix the sarcoplasmic reticulum to T-tubules, and hence the release of Ca2+ in excitation–contraction coupling using pachymic acid (PA) and/or losartan (LN). HF was induced with DOX (3.5 mg/kg, i.p., six doses, twice weekly) in 24 rats. PA and LN (10 mg/kg, daily) were administered orally for four weeks starting the next day of the last DOX dose. Echocardiography, left ventricle (LV) biochemical and histological assessment and electron microscopy were conducted. DOX increased serum BNP, HW/TL, HW/BW, mitochondrial number/size and LV expression of miR-24 but decreased EF, cardiomyocyte fiber diameter, LV content of JP-2 and ryanodine receptors-2 (RyR2). Treatment with either PA or LN reversed these changes. Combined PA + LN attained better results than monotherapies. In conclusion, HF progression following DOX administration can be prevented or even delayed by targeting miR-24 and its downstream JP-2. Our results, therefore, suggest the possibility of using PA alone or as an adjuvant therapy with LN to attain better management of HF patients, especially those who developed tolerance toward LN. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|