Aldosterone modifies hemostasis via upregulation of the protein-C receptor in human vascular endothelium.
In human bone marrow endothelial cell (HBMEC) exposed for 8 h to aldosterone, the microarray screening revealed an upregulation of the mRNAs for six genes and downregulation of mRNAs for four genes, all implicated in hemostasis. In HBMEC, immunocytochemistry revealed the presence of the membrane-bound endothelial protein C receptor (EPCR) whereas the mineralocorticoid receptor (MCR) was present as a nucleo-cytoplasmic. In HBMEC treated with aldosterone the induction of EPCR protein was evident by both FACS analysis and dot blot procedure. When aldosterone-treated HBMEC were incubated with the activated protein C (APC), the partial thromboplastin clotting time (aPTT) increased 2.5-fold over control, from 10 to 25 s. The MCR antagonists aldactone and eplerenone reduced the basal coagulation time in untreated cells to 33.5% and 42% of the control, respectively. These data add an entirely new dimension to delineating the receptor-mediated action of mineralocorticoid hormones.
Ducros
Elodie
E
UMRS 872, Centre de Recherche des Cordeliers, Faculté de Médecine Paris VI, 15 rue de l'Ecole de Médecine, 75006 Paris, France.
Berthaut
Alexandre
A
Mirshahi
Shah Sultan
SS
Faussat
Anne M
AM
Soria
Jeannette
J
Agarwal
Manjul K
MK
Mirshahi
Massoud
M
D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology*; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D001777:Blood Coagulation / Q000187:drug effects / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D000074283:Endothelial Protein C Receptor; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006487:Hemostasis / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D010314:Partial Thromboplastin Time; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone