Effects in postmenopausal women of estradiol and medroxyprogesterone alone and combined on resistance artery function and endothelial morphology and movement.
BACKGROUND
Endothelial dysfunction in resistance arteries after menopause is important for the development of high blood pressure and cardiovascular disease.


OBJECTIVE
Our objectives were to study the effects of different hormone replacement therapies on the function and morphology of isolated resistance arteries, and to look for their mechanistic basis.


METHODS
This was a randomized, placebo-controlled double-blind study in a University hospital, along with laboratory based studies.


METHODS
We isolated resistance arteries in sc biopsies from 55 postmenopausal women before and after 3-month therapy with estradiol (E2), medroxyprogesterone acetate (MPA), E2 plus MPA, or placebo. In addition, we studied isolated human endothelial cells.


RESULTS
Artery flow-mediated dilatation was augmented after treatment with E2 or E2 plus MPA, whereas MPA or placebo had no effect. Pressure-induced myogenic tone was reduced by E2 plus MPA, whereas it was unchanged in the other groups. Scanning microscopy showed that E2 improved endothelial cell morphology and decreased signs of endothelial apoptosis, but the addition of MPA impaired these events. E2, MPA, or the combination all increased the expression and phosphorylation of the actin-binding protein, moesin and of the focal adhesion complex controller, focal adhesion kinase, and induced the rearrangement of cytoskeletal actin and vinculin fibers. All treatments promoted endothelial cell horizontal migration, with E2 inducing the strongest effect.


CONCLUSIONS
This study suggests that hormone replacement therapy with estrogens or in combination with MPA may benefit the function of resistance arteries and may preserve the morphological integrity of endothelial cells by regulatory actions on the cytoskeleton.
Kublickiene
Karolina
K
Department of Clinical Science, Intervention and Technology, Section for Obstetrics and Gynecology, Karolinska Institute, Karolinska University Hospital-Huddinge Campus, 14186 Stockholm, Sweden. karolina.kublickiene@ki.se
Fu
Xiao-Dong
XD
Svedas
Eimantas
E
Landgren
Britt-Marie
BM
Genazzani
Andrea R
AR
Simoncini
Tommaso
T
D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D004311:Double-Blind Method; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008525:Medroxyprogesterone / Q000494:pharmacology*; D008875:Middle Aged; D017698:Postmenopause; D014664:Vasodilation / Q000187:drug effects
D008055:Lipids; D004958:Estradiol; D008525:Medroxyprogesterone