Logo for the Journal of Rehab R&D
Volume 45 Number 2, 2008
Pages 273 — 282

Abstract - Human genome comparison of paretic and nonparetic vastus lateralis muscle in patients with hemiparetic stroke

Michael J. McKenzie, PhD, CSCS;1 Shuzhen Yu, MD;2 Richard F. Macko, MD;1-3 John C. McLenithan, PhD;4 Charlene E. Hafer-Macko, MD1-3*

1Division of Gerontology, University of Maryland School of Medicine, and Baltimore Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs (VA) Maryland Health Care System, Baltimore, MD; 2Department of Neurology, University of Maryland School of Medicine, Baltimore, MD; 3Department of Neurology, VA Maryland Health Care System, Baltimore, MD; 4Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD

Abstract — Hemiparetic stroke leads to major skeletal muscle abnormalities, as illustrated by paretic leg atrophy, weakness, and spasticity. Furthermore, the hemiparetic limb muscle shifts to a fast-twitch muscle fiber phenotype with anaerobic metabolism. This study investigated whether skeletal muscle genes were altered in chronic hemiparetic stroke. The nonparetic leg muscle served as an internal control. We used Affymetrix microarray analysis to survey gene expression differences between paretic and nonparetic vastus lateralis muscle punch biopsies from 10 subjects with chronic hemiparetic stroke. Stroke latency was greater than 6 months. We found that 116 genes were significantly altered between the paretic and nonparetic vastus lateralis muscles. These gene differences were consistent with reported differences after stroke in areas such as injury and inflammation markers, the myosin heavy chain profile, and high prevalence of impaired glucose tolerance and type 2 diabetes. Furthermore, while many other families of genes were altered, the gene families with the most genes altered included inflammation, cell cycle regulation, signal transduction, metabolism, and muscle contractile protein genes. This study is an early step toward identification of specific gene regulatory pathways that might lead to these differences, propagate disability, and increase vascular disease risk.

Key words: cell cycle, gene expression, hemiparetic stroke, inflammation, metabolism, microarray, muscle contraction, rehabilitation, skeletal muscle, transcription factors, vastus lateralis.


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