Stimulated release of endothelin-converting enzyme is simultaneous with tissue-type plasminogen activator and decrease in coronary heart disease.
OBJECTIVE
During the process of atherosclerosis the endothelium changes both structurally and functionally. We examined whether shedding of endothelin-converting enzyme (ECE), a metalloprotease responsible for endothelin production, is concomitant with tissue-type plasminogen activator (t-PA), and how atherosclerosis affects ECE release.


METHODS
Fourteen healthy volunteers and 24 patients with angiographically verified coronary heart disease (CHD) were investigated. ECE and t-PA releases were measured by a provocation test (20-min venous occlusion).


RESULTS
Serum ECE activities were comparable in both groups before the venous occlusion test (in CHD patients 205 +/- 24 vs in healthy controls 204 +/- 40 pmol/ml/h, p = NS). However, delta-ECE (= the difference between, after, and before the venous occlusion test) was significantly lower in CHD patients than in controls (203 +/- 36 vs 338 +/- 43 pmol/ml/h, p = 0.02, respectively). Delta-t-PA was similar in both groups (22.3 +/- 4.4 vs 14.5 +/- 4.6 ng/ml, p = NS, respectively). Furthermore, t-PA and ECE values correlated in the CHD group in all pre-, post-venous occlusion test, and delta-venous occlusion test values (r = 0.56, p = 0.009; r = 0.62, p = 0.003; r = 0.54, p = 0.01, respectively).


CONCLUSIONS
Vascular ECE release can be stimulated, and it is concomitant with t-PA release. A common location in endothelium may explain this simultaneous shedding. However, ECE levels do not rise in patients with CHD as markedly as in healthy patients. Atherosclerosis may explain reduced shedding of ECE.
Sinisalo
Juha
J
Department of Medicine, Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland. juha.sinisalo@hus.fi
Fyhrquist
Frej
F
Syrjälä
Martti
M
Nieminen
Markku S
MS
D000328:Adult; D001161:Arteriosclerosis / Q000503:physiopathology; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D003327:Coronary Disease / Q000503:physiopathology*; D000072396:Endothelin-Converting Enzymes; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases; D008875:Middle Aged; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D010959:Tissue Plasminogen Activator; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes