Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse heart myocardium after a single dose administration of Isoproterenol hydrochloride

ABSTRACT: Gene expression was evaluated in the myocardium of male Wistar rats after a single sc administration of 0.5 mg of isoproterenol, a Î²-adrenergic agonist that causes acute tachycardia with subsequent myocardial necrosis. Histology of the heart, clinical chemistry and hematology were evaluated at 9 time-points (0.5 hr to 14 d post-injection). Myocardial gene expression was evaluated at 4 time-points (1 hr to 3 d). Contraction bands and loss of cross striation were identified on phosphotungstic acid-hematoxylin-stained sections 0.5 hr post-dosing. Plasma troponin I elevation was detected at 0.5 hr, peaked at 3 hr, and returned to baseline values at 3 d post-dosing. Interleukin 6 (Il6) expression spiked at 1-3 hr and was followed by a short-lived time-dependant dysregulation of its downstream targets. Concurrently and consistent with the kinetics of the histologic findings, many pathways indicative of necrosis/apoptosis (p38 MAPK signaling, NF-kB signaling) and adaptation to hypertension (PPAR signaling) were over-represented at 3 hr. The 1 d and 3 d time-points indicated an adaptative response, with down-regulation of the fatty acid metabolism pathway, up-regulation of the fetal gene program, and superimposed inflammation and repair at 3 d. These results suggest early involvement of Il6 in isoproterenol-induced myocardial necrosis and emphasize the value of early time-points in transcriptomic studies Experiment Overall Design: Myocardial gene expression was evaluated at 4 time-points: 1 hour, 3 hours, 24 hours and 48 hours for doses of 0mg and 0.5 mg Isoproternol.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Charu Kanwal

PROVIDER: E-GEOD-7999 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Myocardial ischemic preconditioning (IPC) enhances myocardial resilience to ischemic injury. Myocardial stunning is a transient, reversible dysfunction, while necrosis involves irreversible cell death. The relationship between IPC, stunning, and necrosis is not well understood, requiring further molecular investigation. This study aimed to investigate the proteomic changes associated with IPC, focusing on its relationship with myocardial stunning and necrosis. A novel 13.5-minute ischemia-reperfusion (I/R) rat model was specifically chosen to induce myocardial stunning, providing a unique approach to assess IPC effects in this context. Rats underwent either IPC with two 5-minute ischemia/reperfusion cycles followed by a 13.5-minute ischemic period or the procedure without IPC (no ischemic preconditioning, NIPC). Myocardial samples were collected at early (T1) and 4-hour post-reperfusion (T2) time points for proteomic analysis. Protein levels were quantified by differential labeling using TMTpro reagents, and subsequent liquid chromatography-mass spectrometry. IPC induced upregulation of proteins involved in endocytosis and Fc gamma R-mediated phagocytosis pathways at T1, while downregulating proteins related to tissue remodeling, immune response, and coagulation at T2. Conversely, NIPC exhibited upregulation of proteins associated with tissue damage and inflammation. IPC rats demonstrated enhanced leukocyte migration, complement activation, and immune response between T1 and T2. Consistent proteomic changes were observed between T1 and T2 in IPC vs. NIPC groups, and common alterations between IPC T2 vs. T1 and NIPC T2 vs. T1 comparisons underline shared pathways in cardiac complement and coagulation cascades. Our study reveals distinct proteomic changes induced by IPC in the context of myocardial stunning and necrosis. IPC activates early protective pathways, attenuates tissue damage and inflammation, and preserves myocardial function. These findings underscore IPC's reparative potential and identify myocardial stunning as an important, transient adaptation, which may have implications for supportive clinical management in I/R.

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Transcription profiling of mouse heart myocardium after a single dose administration of Isoproterenol hydrochloride

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