+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Sex steroids modulate human aortic smooth muscle cell matrix protein deposition and matrix metalloproteinase expression



Sex steroids modulate human aortic smooth muscle cell matrix protein deposition and matrix metalloproteinase expression



Hypertension 46(5): 1129-1134



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 17beta-estradiol, progesterone, 17beta-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%; 17beta-estradiol plus progesterone, 20+/-2%; testosterone 74+/-12%, P<0.001). Female sex steroids increased elastin deposition compared with control (control, 100%; 17beta-estradiol, 540+/-60%; progesterone, 290+/-40%; 17beta-estradiol plus progesterone, 400+/-80%, all P<0.01). The elastin/collagen ratio was >11-fold higher in the presence of 17beta-estradiol and progesterone compared with testosterone. Fibrillin-1 deposition was doubled in the presence of female sex steroids (17beta-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.

(PDF emailed within 0-6 h: $19.90)

Accession: 012552077

Download citation: RISBibTeXText

PMID: 16230520

DOI: 10.1161/01.hyp.0000187016.06549.96


Related references

Abdominal Aortic Aneurysm-Associated MicroRNA-516a-5p Regulates Expressions of Methylenetetrahydrofolate Reductase, Matrix Metalloproteinase-2, and Tissue Inhibitor of Matrix Metalloproteinase-1 in Human Abdominal Aortic Vascular Smooth Muscle Cells. Annals of Vascular Surgery 42: 263-273, 2017

Activated factor-X promotes release of active matrix metalloproteinase-2 from human vascular smooth muscle cell and directly cleaves secreted pro-matrix metalloproteinase-2. Circulation 104(17 Supplement): II 259, October 23, 2001

Development-related changes in matrix metalloproteinase expression in human aortic smooth muscle cells. Laboratory Investigation. 71(2): 261-269, 1994

Mechanism of inhibition of matrix metalloproteinase-2 expression by doxycycline in human aortic smooth muscle cells. Journal of Vascular Surgery 38(6): 1376-1383, 2003

Toll-like receptors 4 induces expression of matrix metalloproteinase-9 in human aortic smooth muscle cells. Molecular Biology Reports 38(2): 1419-1423, 2011

Possible involvement of Cyclic-GMP-dependent protein kinase on matrix metalloproteinase-2 expression in rat aortic smooth muscle cells. Molecular and Cellular Biochemistry 368(1-2): 27-35, 2012

Angiotensin II increases matrix metalloproteinase 2 expression in human aortic smooth muscle cells via AT1R and ERK1/2. Experimental Biology and Medicine 240(12): 1564-1571, 2016

Carnosic acid prevents the migration of human aortic smooth muscle cells by inhibiting the activation and expression of matrix metalloproteinase-9. British Journal of Nutrition 100(4): 731-738, 2008

Matrix metalloproteinase 2 and matrix metalloproteinase 9 expression in human oral squamous cell carcinoma and the effect of protein kinase C inhibitors: preliminary observations. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics 95(6): 710-716, 2003

Human thyroid carcinoma cell lines and normal thyrocytes: expression and regulation of matrix metalloproteinase-1 and tissue matrix metalloproteinase inhibitor-1 messenger-RNA and protein. Thyroid 7(5): 713-724, 1998

Factor-Xa cleaves secreted pro-matrix metalloproteinase-2 and releases active matrix metalloproteinase-2 from human vascular smooth muscle cells. Naunyn-Schmiedeberg's Archives of Pharmacology 365(Supplement 1): R99, 2002

ETS-1 protein regulates vascular endothelial growth factor-induced matrix metalloproteinase-9 and matrix metalloproteinase-13 expression in human ovarian carcinoma cell line SKOV-3. Journal of Biological Chemistry 287(18): 15001-15015, 2012

Matrix metalloproteinase 2 and tissue inhibitors of metalloproteinases regulate human aortic smooth muscle cell migration during in vitro aging. Faseb Journal 20(8): 1118-1130, 2006

Inhibitory effect of Cho-Deung-San on human aortic smooth muscle cell migration induced by TNF-alpha through inhibition of matrix metalloproteinase-2 and -9 activity. Vascular Pharmacology 41(3): 83-90, 2004

Red wine polyphenolic compounds strongly inhibit pro-matrix metalloproteinase-2 expression and its activation in response to thrombin via direct inhibition of membrane type 1-matrix metalloproteinase in vascular smooth muscle cells. Circulation 110(13): 1861-1867, 2004