Abstract 027: Participation of Cardiac Thyrotroping Releasing Hormone (cTRH) in the Doxorrubicin (D) Induced Cardiotoxicityin in Mice
| Autor: | Mariano Luis Schuman, Ludmila S. Peres Diaz, Silvia I. García, Maria Silvina Landa, Maia Aisicovich |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
endocrine system
medicine.medical_specialty Cardiotoxicity business.industry Caspase 3 medicine.disease Muscle hypertrophy chemistry.chemical_compound Endocrinology chemistry Apoptosis Fibrosis Internal medicine Gene expression Internal Medicine medicine business Sirius Red hormones hormone substitutes and hormone antagonists Hormone |
| Zdroj: | Hypertension. 68 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hyp.68.suppl_1.027 |
| Popis: | We have demonstrated TRH hyperactivity in the hypertrophied Left ventricle (LV) of SHR. Its specific inhibition attenuates hypertrophy development in spite of the significant higher pressure observed (Schuman M, Hypertension 2011). LV-TRH over-expression induces several features of the hypertrophied heart, including increases in the apoptotic index Bax/Bcl2, and the activated caspase 3 observed by immunohystochemistry (Schuman M, AJPH&C 2014). In addition, we have found that TRH expression was induced by D in primary cultures of cardiac cells. Based on these results we hypothesized that cTRH could participate in the D cardiotoxicity effects. Indeed, we used C57 adult males (n=10) with a single D or saline injection (200uL,10 mg/kg ip) which previously (24 h, under anesthesia) received an intracardiac injection of a specific TRH-siRNA to inhibit LV-TRH expression or scrambled Con-siRNA. Mice were sacrificed 2,4 and 7 days post D injection and body weight was measured. Genes expression was measured by real time PCR and protein by immunohystochemistry (ANOVA and Tukey test). Body weight showed a mild but not significant decrease in D treated animals. D significantly increased TRH gene expression and TRH protein content reaching the maximum at 7 days post injection (2d: 145%, 4d:190% and 7d: 250%) (p& 0.05), which were not observed in the groups with D+TRH-siRNA indicating the effectiveness of the specific TRH inhibition. Also at this time TRH inhibition attenuates (p&0.05) D-induced increase in the apoptotic index Bax/Bcl2 and the augmented activated caspase 3 content pointing out the participation of the cardiac TRH in the D-induced apoptosis. Similar results were observed with hypertrophic and fibrotic markers gene expression (BNP, BMHC and col III) which showed a significant increase (p& 0.05) only in the groups with D and the intact TRH system (D+Con-siRNA). Fibrosis results were confirmed by Sirius Red and Masson techniques. On the whole, we demonstrated for the first time that LV-TRH system is required for both, Doxorrubicin induction of apoptosis and consecutively hypertrophy and fibrosis in the mouse heart. Even more, we found that cTRH inhibition attenuates doxorrubicin induced damage suggesting a novel mechanisms in the cardiotoxicity injury. |
| Databáze: | OpenAIRE |
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