Microsoft Word - 300806-R1_PAP_01_10_13
نویسندگان
چکیده
Rationale: During the transition from compensated hypertrophy to heart failure, the signaling between L-type Ca 2+ channels (LCCs) in the cell membrane/T-tubules (TTs) and ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR) becomes defective, partially due to the decreased expression of a TT-SR anchoring protein, junctophilin-2 (JP2). MiR-24, a JP2 suppressing microRNA, is up-regulated in hypertrophied and failing cardiomyocytes. Objective: To test whether miR-24 suppression can protect the structural and functional integrity of LCC-RyR signaling in hypertrophied cardiomyocytes. Methods and Results: In vivo silencing of miR-24 by a specific antagomir in an aorta-constricted mouse model effectively prevented the degradation of heart contraction but not ventricular hypertrophy. Electrophysiology and confocal imaging studies showed that antagomir treatment prevented the decreases in LCC-RyR signaling fidelity/efficiency and whole-cell Ca 2+ transients. Further studies showed that antagomir treatment stabilized JP2 expression and protected the ultrastructure of TT-SR junctions from disruption. Conclusions: MiR-24 suppression prevented the transition from compensated hypertrophy to decompensated hypertrophy, providing a potential strategy for early treatment against heart failure.
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Introduction to Accessible Education [2] Developing Courses [3] Writing a Course Syllabus [4] Creating Accessible Lectures [5] Using PowerPoint [6] Using Word Documents and/or PDFs [7] Microsoft Word Accessibility Video pt 1 [8] Microsoft Word Accessibility Video pt 2 [9] Evaluating Students and Giving Feedback [10] Using Microsoft Office Microsoft Office 2010 Accessibility Video [11] Microsoft...
متن کاملAccessible Instruction - Resources
Introduction to Accessible Education [2] Developing Courses [3] Writing a Course Syllabus [4] Creating Accessible Lectures [5] Using PowerPoint [6] Using Word Documents and/or PDFs [7] Microsoft Word Accessibility Video pt 1 [8] Microsoft Word Accessibility Video pt 2 [9] Evaluating Students and Giving Feedback [10] Using Microsoft Office Microsoft Office 2010 Accessibility Video [11] Microsoft...
متن کاملAccessible Instruction - Resources
Introduction to Accessible Education [2] Developing Courses [3] Writing a Course Syllabus [4] Creating Accessible Lectures [5] Using PowerPoint [6] Using Word Documents and/or PDFs [7] Microsoft Word Accessibility Video pt 1 [8] Microsoft Word Accessibility Video pt 2 [9] Evaluating Students and Giving Feedback [10] Using Microsoft Office Microsoft Office 2010 Accessibility Video [11] Microsoft...
متن کاملAccessible Instruction - Resources
Introduction to Accessible Education [2] Developing Courses [3] Writing a Course Syllabus [4] Creating Accessible Lectures [5] Using PowerPoint [6] Using Word Documents and/or PDFs [7] Microsoft Word Accessibility Video pt 1 [8] Microsoft Word Accessibility Video pt 2 [9] Evaluating Students and Giving Feedback [10] Using Microsoft Office Microsoft Office 2010 Accessibility Video [11] Microsoft...
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