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Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix
Published on: June 14, 2016
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Dysfunction of the β2-spectrin-based pathway in human heart failure
Sakima A Smith1, Langston D Hughes2, Crystal F Kline3
1Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio; Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio; Sakima.smith@osumc.edu.
Summary
Beta2-spectrin levels decrease in cardiovascular disease, including atrial fibrillation and heart failure. This reduction is linked to calcium and calpain activity, affecting key proteins like ankyrin-B.
Area of Science:
- Cardiovascular Biology
- Cellular and Molecular Medicine
- Biochemistry
Background:
- Beta2-spectrin is essential for cell structure and function, particularly in integrating membrane and cytoskeletal domains.
- Dysfunction in beta2-spectrin pathways is linked to various diseases, including congenital heart arrhythmias due to ankyrin-B association defects.
- The role of beta2-spectrin in acquired heart failure and common arrhythmias remains largely unknown.
Purpose of the Study:
- To investigate the role and regulation of beta2-spectrin in acquired cardiovascular diseases, specifically heart failure and atrial fibrillation.
- To determine if beta2-spectrin levels are altered in human cardiovascular disease and animal models.
- To elucidate the posttranslational mechanisms regulating beta2-spectrin in the context of heart conditions.
Main Methods:
- Analysis of beta2-spectrin protein levels in human atrial and left ventricular tissue samples from patients with cardiovascular disease and healthy controls.
- Examination of beta2-spectrin levels in large and small animal models of heart failure (canine and murine).
- Investigation of posttranslational modifications, specifically calcium (Ca2+) and calpain protease activity, on beta2-spectrin and its downstream effectors.
Main Results:
- Beta2-spectrin protein levels were significantly decreased in atrial fibrillation patients compared to those in sinus rhythm.
- Left ventricular beta2-spectrin levels were significantly reduced in patients with ischemic and non-ischemic heart failure.
- Reduced beta2-spectrin protein levels were confirmed in canine and murine heart failure models.
- Beta2-spectrin levels are regulated by Ca2+- and calpain-dependent proteases.
- Ca2+- and calpain-dependent degradation of beta2-spectrin and its downstream effector ankyrin-B was observed in the heart.
Conclusions:
- Beta2-spectrin levels are significantly altered in various forms of acquired cardiovascular disease, including atrial fibrillation and heart failure.
- The reduction of beta2-spectrin in cardiovascular disease is mediated by posttranslational mechanisms involving Ca2+ and calpain proteases.
- These findings highlight a novel regulatory pathway for beta2-spectrin and its associated proteins in the pathogenesis of heart conditions.
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