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(Hypertension. 2005;46:1129.)
© 2005 American Heart Association, Inc.

Original Articles

Sex Steroids Modulate Human Aortic Smooth Muscle Cell Matrix Protein Deposition and Matrix Metalloproteinase Expression

Alaina K. Natoli; Tanya L. Medley; Anna A. Ahimastos; Brian G. Drew; Daniel J. Thearle; Rodney J. Dilley; Bronwyn A. Kingwell

From the Baker Heart Research Institute (A.K.N., T.L.M., A.A.A., B.G.D., D.J.T., B.A.K.), and University of Melbourne, Department of Medicine, St. Vincent’s Hospital (R.J.D.), Victoria, Australia.

Correspondence to Bronwyn Kingwell, Alfred and Baker Medical Unit, Baker Medical Research Institute, P.O. Box 6492, St Kilda Rd Central, Melbourne, Victoria, 8008 Australia. E-mail b.kingwell{at}alfred.org.au

Large artery stiffening increases cardiovascular risk and promotes isolated systolic hypertension which is more prevalent in elderly women than men. Variation in sex steroid levels between males and females and throughout life may modulate arterial stiffness. We hypothesized that sex steroids directly influence expression of important structural proteins which determine arterial biomechanical properties. Human aortic smooth muscle cells were incubated with physiological concentrations of 17ß-estradiol, progesterone, 17ß-estradiol and progesterone, or testosterone for 4 weeks. Collagen, elastin, and fibrillin-1 deposition was examined (histochemistry/immunohistochemistry). Gene and protein expression of 2 important matrix metalloproteinases (MMPs), MMPs 2 and 3, regulating matrix turnover was assessed. All sex steroids reduced collagen deposition relative to control (100%). However, the reduction was greater with female sex steroids than testosterone (control, 100%; 17ß-estradiol plus progesterone, 20±2%; testosterone 74±12%, P<0.001). Female sex steroids increased elastin deposition compared with control (control, 100%; 17ß-estradiol, 540±60%; progesterone, 290±40%; 17ß-estradiol plus progesterone, 400±80%, all P<0.01). The elastin/collagen ratio was >11-fold higher in the presence of 17ß-estradiol and progesterone compared with testosterone. Fibrillin-1 deposition was doubled in the presence of female sex steroids (17ß-estradiol plus progesterone) compared with testosterone (P<0.01). MMP-2 gene and protein expression was unaffected by any sex steroid. Testosterone increased both gene and protein expression of MMP-3 relative to both control and female sex steroids (P<0.01). This may contribute to degradation of elastic matrix proteins. In conclusion, female sex steroids promote an elastic matrix profile, which likely contributes to variation in large artery stiffness observed between sexes and with changes in hormonal status across the lifespan.

Key Words: collagen • elastin • sex • arterial stiffness

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