Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Role of endothelial cell apoptosis in regulation of skeletal muscle angiogenesis during high and low salt intake. Physiol Genomics 2006 Apr 13;25(2):325-35 PMID: 16464974


Angiogenesis, under normal conditions, is a tightly regulated balance between pro- and antiangiogenic factors. The goal of this study was to investigate the mechanisms involved in the control of the skeletal muscle angiogenic response induced by electrical stimulation during the suppression of plasma renin activity (PRA) with a high-salt diet. Rats fed 0.4% or 4% salt diets were exposed to electrical stimulation for 7 days. The tibialis anterior (TA) muscles from stimulated and unstimulated hindlimbs were removed and prepared for gene expression analysis, CD31-terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) double-staining assay, and Bcl-2 and Bax protein expression by Western blot. Rats fed a low-salt diet showed a dramatic angiogenesis response in the stimulated limb compared with the unstimulated limb. This angiogenesis response was significantly attenuated when rats were placed on a high-salt diet. Microarray analysis showed that in the stimulated limb of rats fed a low-salt diet many genes related to angiogenesis were upregulated. In contrast, in rats fed a high-salt diet most of the genes upregulated in the stimulated limb function in apoptosis and cell cycle arrest. Endothelial cell apoptosis, as analyzed by CD31-TUNEL staining, increased by fourfold in the stimulated limb compared with the unstimulated limb. There was also a 48% decrease in the Bcl-2-to-Bax ratio in stimulated compared with unstimulated limbs of rats fed a high-salt diet, confirming severe apoptosis. This study suggests that the increase in endothelial cell apoptosis in TA muscle might contribute to the attenuation of angiogenesis response observed in rats fed a high-salt diet.

Author List

de Resende MM, Amaral SL, Munzenmaier DH, Greene AS


Andrew S. Greene PhD Interim Vice Chair, Chief, Professor in the Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Dose-Response Relationship, Drug
Electric Stimulation
Endothelial Cells
Gene Expression Profiling
Gene Expression Regulation
Muscle, Skeletal
Neovascularization, Physiologic
Oligonucleotide Array Sequence Analysis
Proto-Oncogene Proteins c-bcl-2
Rats, Inbred BN
Rats, Inbred Dahl
Sodium Chloride, Dietary
Time Factors
bcl-2-Associated X Protein

View this publication's entry at the Pubmed website PMID: 16464974
jenkins-FCD Prod-185 20a1a87aaef305b3f5a3e8bb55f731baa68cadd0