Medroxyprogesterone acetate enhances monocyte-endothelial interaction under flow conditions by stimulating the expression of cell adhesion molecules.

Abstract

CONTEXT:

Monocyte adhesion to endothelial cells is an important initial event in atherosclerosis and is partially mediated by adhesion molecule expression on the cell surface. Although estrogens inhibit atherosclerosis development, effects of coadministered progestogen remain controversial.

OBJECTIVE:

We examined the effects of progestogen on cytokine-stimulated human umbilical venous endothelial cell (HUVEC) expression of adhesion molecules.

DESIGN:

In HUVECs, adhesion molecule mRNA levels were measured by real-time PCR. Protein expression was quantified by immunocytochemistry and ELISAs. To mimic the monocyte adherence to endothelial cells, we used a flow chamber system to assess progestogen effects on U937 monocytoid cell adherence to HUVEC monolayers. We also examined the suppression effects of adhesion molecules with small interference RNAs.

RESULTS:

mRNA levels of adhesion molecules in HUVECs treated with medroxyprogesterone acetate (MPA) or 17β-estradiol + MPA were 1.7- to 2.5-fold higher than those in the control. MPA increased the protein expression of E-selectin, P-selectin, and intercellular adhesion molecule-1 compared with that for the control (83.0 ± 0.7, 34.8 ± 1.2, and 5.4 ± 0.0 ng/mL, respectively), whereas other progestogens or 17β-estradiol additive to progestogens did not significantly change expression. MPA significantly increased U937 monocytoid cell adherence compared with the control (56.0 ± 1.5 vs 46.5 ± 3.5 adherent cells per 10 fields) but did not increase adherence to HUVECs with knocked down intercellular adhesion molecule-1.

CONCLUSIONS:

MPA increases cell adhesion molecule expression on HUVECs, causing increased numbers of monocytoid cells to adhere to HUVECs. These MPA effects may be a risk factor for atherogenesis on endothelial cells in postmenopausal women receiving hormone replacement therapy.

• Authors: Fumitake Ito, Hiroshi Tatsumi, Taisuke Mori, Izumi Suganuma, Yukiko Tanaka, Aya Sasaki, Seiki Matsuo, Koichi Iwasa, Jo Kitawaki
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 99 Issue 6 Pg. 2188-97 (Jun 2014) ISSN: 1945-7197 [Electronic] United States
• PMID: 24606071 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Adhesion Molecules
• Medroxyprogesterone Acetate

Topics

• Cell Adhesion Molecules (genetics, metabolism)
• Cell Communication (drug effects)
• Cell Culture Techniques
• Cells, Cultured
• Endothelium, Vascular (cytology, drug effects, metabolism)
• Female
• Gene Expression Regulation (drug effects)
• Human Umbilical Vein Endothelial Cells (drug effects, physiology)
• Humans
• Infant, Newborn
• Medroxyprogesterone Acetate (pharmacology)
• Monocytes (drug effects, physiology)
• U937 Cells