Angiotensin-converting enzyme gene expression in skeletal muscle in patients with chronic heart failure.
BACKGROUND
Skeletal muscle factors may influence functional limitation in patients with heart failure. The renin-angiotensin system is activated in chronic heart failure. Treatment with angiotensin-converting enzyme (ACE) inhibitors improve symptoms and prognosis. The goal of this study was to quantify and localize skeletal muscle ACE-mRNA in patients with chronic heart failure and in control subjects, and to elucidate skeletal muscle fiber area and capillary density.


RESULTS
Biopsies from the lateral vastus muscle were taken from 9 patients before and after treatment with enalapril and in 10 control subjects. ACE-mRNA was quantified with reverse transcription polymerase chain reaction. Immunohistochemistry was used to localize ACE within skeletal muscle. No difference in ACE-mRNA transcripts between patients and control subjects was detected, nor did ACE gene expression change after treatment with enalapril. The number of ACE-mRNA transcripts was related to muscle fiber area, whereas an inverse relationship between the number of ACE transcripts and capillary density was found. ACE was detected in the endothelial cells of capillaries in skeletal muscle.


CONCLUSIONS
ACE is expressed in skeletal muscle and is confined to endothelial cells. The close relationship between capillary density and number of ACE transcripts indicate that activation of the renin-angiotensin system has an impact on capillary growth.
Schaufelberger
M
M
Department of Medicine, Sahlgrenska University Hospital/Ostra, Göteborg University, Sweden.
Drexler
H
H
Schieffer
E
E
Swedberg
K
K
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000032:analysis; D000368:Aged; D000804:Angiotensin II / Q000032:analysis*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D001706:Biopsy; D002196:Capillaries / Q000737:chemistry / Q000473:pathology; D002950:Citrate (si)-Synthase / Q000032:analysis; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000187:drug effects / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D014157:Transcription Factors / Q000032:analysis
D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D014157:Transcription Factors; D000804:Angiotensin II; D004656:Enalapril; D015094:3-Hydroxyacyl CoA Dehydrogenases; D002950:Citrate (si)-Synthase; D007703:Peptidyl-Dipeptidase A