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Yang Lee, M.S.


Heart cells (myocytes) have distinctive shapes, structural integrity, and functions that are maintained by proteins that are part of the “cytoskeleton”. The cytoskeleton is scaffolding or framework around the cells serves to stabilize cells and tissues and regulate internal function of the cells. The dystrophin-glycoprotein complex (DGC) is a structure comprised of proteins on the outer side of the cell membrane that links the cell and its cytoskeleton to the connective tissue around heart cells. In skeletal muscle, impairment of the DGC results in muscle myopathy (muscle weakness) and fibrosis (accumulation of fibrous protein, collagen), and contributes to muscle atrophy and many of the muscular dystrophies. Our lab’s research data show that the DGC is disrupted in muscles as people grow older, leading to weakness. Aging causes fibrosis and weakness of myocytes in the heart, resulting in arrhythmias with increased risk of heart disease and heart failure. Recent studies show that the disruption of DGC through the aging process may contribute to fibrosis and thus to cardiomyopathy and heart failure. For example, impaired DGC proteins do not allow a part of the muscle, the Z disc, to hold together actin filaments and transmit tension, leading to contractile dysfunction. Without an intact DGC, filling the heart with blood and pumping it are poor. Recently, our laboratory has found that exercise training, diet, and drug treatment (e.g., antioxidant drugs) can prevent cardiac DGC disruption linked to reduced fibrosis of the heart. Specifically, we found that 12 weeks of endurance exercise training in old rats reversed a reduction in the level of three DGC proteins (dystrophin, syntrophin, and sarcoglycan) found near the cell membrane. This research shows not only that exercise reduces fibrosis in the aging heart but precisely how it does so. This is important because in better understanding how exercise works, we can develop targeted drugs that will work synergistically with exercise training to mitigate the risk of heart disease and heart failure. The result is improved quality of life and vitality for seniors.

 

For more information, read these additional references:

  1. Dalakas, M. C., Park, K.-Y., Semino-Mora, C., Lee, H. S., Sivakumar, K., & Goldfarb, L. G. (2000). Desmin Myopathy, a Skeletal Myopathy with Cardiomyopathy Caused by Mutations in the Desmin Gene. New England Journal of Medicine, 342(11), 770-780. http://www.nejm.org/doi/pdf/10.1056/NEJM200003163421104
  2. Kakarla, S. K., Rice, K. M., Katta, A., Paturi, S., Wu, M., Kolli, M., . . . Blough, E. R. (2010). Possible Molecular Mechanisms Underlying Age-Related Cardiomyocyte Apoptosis in the F344XBN Rat Heart. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 65A(2), 147-155. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806239/pdf/glp203.pdf
  3. Kwak, H.-B., Kim, J.-h., Joshi, K., Yeh, A., Martinez, D. A., & Lawler, J. M. (2011). Exercise training reduces fibrosis and matrix metalloproteinase dysregulation in the aging rat heart. The FASEB Journal, 25(3), 1106-1117. http://www.fasebj.org/content/25/3/1106.full.pdf+html
  4. Shin, J. H., Nitahara-Kasahara, Y., Hayashita-Kinoh, H., Ohshima-Hosoyama, S., Kinoshita, K., Chiyo, T., . . . Takeda, S. (2011). Improvement of cardiac fibrosis in dystrophic mice by rAAV9-mediated microdystrophin transduction. Gene Ther, 18(9), 910-919. http://www.nature.com/gt/journal/v18/n9/pdf/gt201136a.pdf
  • Cytoskeleton Protection by Exercise Training in the Aging Heart


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