Angiotensin converting enzyme: an in vivo and in vitro marker of endothelial injury.
An elevated level of von Willebrand factor (vWf) is a well-established marker for both in vivo and in vitro endothelial cell injury. Recent studies indicate that the plasma level of angiotensin-converting enzyme (ACE) in systemic sclerosis is reduced in association with elevated vWf levels. Because the endothelial cell is capable of producing both mediators, and because endothelial cell injury is a fundamental process in systemic sclerosis, we investigated in this study the effect of in vitro endothelial cell injury on the synthesis of both factors. Endothelial cells derived from human umbilical veins, in the second passage, were activated by exposure to interleukin-1 or lymphotoxin or were injured by radiation, actinomycin, or trypsin (each can be shown to induce dose-dependent endothelial cell cytotoxicity). ACE (spectrophotometric method) and vWf levels (enzyme-linked immunosorbent assay method) were determined in the supernatant and in the cell lysate 48 hours after cellular injury and activation. An increase in vWf levels was found in the lysate and in the supernatant from the cells that underwent injury or activation, whereas ACE levels were increased after activation but decreased after injury. Next, and as an in vivo clinical corollary to the in vitro endothelial cell injury, we evaluated ACE and vWf levels in the plasma of seven children in the acute phase of Kawasaki disease, a disorder characterized by widespread vascular injury. Plasma ACE levels were significantly lower than control levels, whereas vWf levels were increased, reflecting the known prominent endothelial cell injury in this disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Matucci-Cerinic
M
M
Institute of Internal Medicine IV, University of Florence, Italy.
Jaffa
A
A
Kahaleh
B
B
D002478:Cells, Cultured; D002648:Child; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology* / Q000528:radiation effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis* / Q000187:drug effects / Q000528:radiation effects; D014471:Umbilical Veins / Q000378:metabolism / Q000473:pathology; D014841:von Willebrand Factor / Q000096:biosynthesis
D007375:Interleukin-1; D008233:Lymphotoxin-alpha; D014841:von Willebrand Factor; D007703:Peptidyl-Dipeptidase A