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Am J Physiol Heart Circ Physiol (January 9, 2003). doi:10.1152/ajpheart.00958.2002
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Submitted on November 6, 2002
Accepted on January 3, 2003

Effects of Ovariectomy on Aggregation, Secretion, and Metalloproteinases in Porcine Platelets

Muthuvel Jayachandran1, Whyte G. Owen2, and Virginia M. Miller1*

1 Department of Surgery, Mayo Clinic Rochester, Rochester, MN, USA
2 Department of Physiology and Biophysics, Mayo Clinic Rochester, Rochester, MN, USA

* To whom correspondence should be addressed. E-mail: miller.virginia{at}mayo.edu.

Differences in aggregation and release of growth factors including matrix metalloproteinases (MMPs) following loss of ovarian hormones could contribute to exaggerated response to injury in arteries of ovariectomized animals. Therefore, experiments were designed to compare aggregation, dense granular ATP release, expression of matrix metalloproteinases (MMP-2, -9, -14) and tissue inhibitors of metalloproteinase-1 (TIMP-1), TIMP-2 in circulating platelets from sexually mature (7-month-old), gonadally intact and ovariectomized (4 weeks), female pigs. Numbers of circulating platelets did not change following ovariectomy but percent of reticulated platelets increased significantly. Platelet aggregation and dense granular ATP secretion also increased significantly with ovariectomy. In platelet lysates, active MMP-2 increased whereas MMP-14 decreased significantly following ovariectomy; expression of TIMP-1, -2, and P-selectin did not change. These results suggest that platelet turnover, aggregation and ATP secretion increase with ovariectomy. Also, ovarian hormones selectively regulate expression and activity of MMPs in porcine platelets. Increased platelet aggregation and activity of MMP-2 would alter platelet-platelet and platelet-vessel wall interactions, contributing to exaggerated response to injury with loss of ovarian hormones.




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