Conjugated equine estrogens inhibit progression of atherosclerosis but have no effect on intimal hyperplasia or arterial remodeling induced by balloon catheter injury in monkeys

Comparative Medicine Clinical Research Center and Division of Surgical Sciences-General, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157-1040, USA.

OBJECTIVES: This study sought to determine the effects of estrogen treatment on atherosclerosis progression and the proliferative and structural responses of the atherosclerotic arteries to injury. BACKGROUND: Estrogen treatment suppresses the intimal response to arterial injury in nonatherosclerotic rodents and rabbits and inhibits the in vitro proliferation of smooth muscle cells. However, the effect of estrogen on the response of atherosclerotic arteries to transmural injury, as occurs in balloon catheter angioplasty in humans, is unknown. METHODS: Forty-six ovariectomized cynomolgus monkeys were fed an atherogenic diet for 30 months; 25 received 175 microg/day of conjugated equine estrogens, and 21 served as untreated control animals. All animals underwent balloon catheter injury of the left iliac artery. Subsets of animals underwent a necropsy study at 4, 7, 14 and 28 days after injury; injured and contralateral (uninjured) arteries were pressure-fixed and evaluated morphometrically. RESULTS: Estrogen treatment resulted in a 37% decrease (p < 0.05) in atherosclerosis (plaque area) in the uninjured artery. In response to injury, arterial cell proliferation increased at days 4 and 7, and intimal area was increased two- to threefold at day 28 (p < 0.05). Although estrogen treatment resulted in a trend toward decreased arterial cell proliferation at day 4, there was evidence of increased cell proliferation in both media and intima at day 7 (p < 0.05). However, there was no effect of estrogen treatment on intimal area or indexes of arterial remodeling in the injured artery at day 28 (p > 0.4). CONCLUSIONS. In contrast to previous studies of nonatherosclerotic animals, the results indicate that in the circumstance of transmural injury to arteries of primates with preexisting atherosclerosis, estrogen does not suppress arterial neointimal or structural responses to injury.

This article has been cited by other articles:

				A. G. Touchard and R. S. Schwartz Preclinical Restenosis Models: Challenges and Successes Toxicol Pathol, January 1, 2006; 34(1): 11 - 18. [Abstract] [Full Text] [PDF]

				R. K. Dubey, B. Imthurn, M. Barton, and E. K. Jackson Vascular consequences of menopause and hormone therapy: Importance of timing of treatment and type of estrogen Cardiovasc Res, May 1, 2005; 66(2): 295 - 306. [Abstract] [Full Text] [PDF]

				R. K. Dubey, B. Imthurn, L. C. Zacharia, and E. K. Jackson Hormone Replacement Therapy and Cardiovascular Disease: What Went Wrong and Where Do We Go From Here? Hypertension, December 1, 2004; 44(6): 789 - 795. [Abstract] [Full Text] [PDF]

				H. C. Lowe, S. N. Oesterle, and L. M. Khachigian Coronary in-stent restenosis: Current status and future strategies J. Am. Coll. Cardiol., January 16, 2002; 39(2): 183 - 193. [Abstract] [Full Text] [PDF]

				G. S. Cherr, S. J. Motew, J. A. Travis, J. Fingerle, L. Fisher, M. Brandl, J. K. Williams, and R. L. Geary Metalloproteinase Inhibition and the Response to Angioplasty and Stenting in Atherosclerotic Primates Arterioscler. Thromb. Vasc. Biol., January 1, 2002; 22(1): 161 - 166. [Abstract] [Full Text] [PDF]

				R. K. Dubey and E. K. Jackson Estrogen-induced cardiorenal protection: potential cellular, biochemical, and molecular mechanisms Am J Physiol Renal Physiol, March 1, 2001; 280(3): F365 - F388. [Abstract] [Full Text] [PDF]

				B. Chandrasekar and J.-F. Tanguay Local delivery of 17-beta-estradiol decreases neointimal hyperplasia after coronary angioplasty in a porcine model J. Am. Coll. Cardiol., November 15, 2000; 36(6): 1972 - 1978. [Abstract] [Full Text] [PDF]

				S. Oparil Hormones and Vasoprotection Hypertension, January 1, 1999; 33(1): 170 - 176. [Abstract] [Full Text] [PDF]

				P. Holm, H. L. Andersen, G. Arroe, and S. Stender Gender Gap in Aortic Cholesterol Accumulation in Cholesterol-Clamped Rabbits : Role of the Endothelium and Mononuclear-Endothelial Cell Interaction Circulation, December 15, 1998; 98(24): 2731 - 2737. [Abstract] [Full Text] [PDF]

				J. S. Deitch, J. K. Williams, M. R. Adams, C. A. Fly, D. M. Herrington, R. E. Jordan, M. T. Nakada, J. A. Jakubowski, and R. L. Geary Effects of ß3-Integrin Blockade (c7E3) on the Response to Angioplasty and Intra-Arterial Stenting in Atherosclerotic Nonhuman Primates Arterioscler. Thromb. Vasc. Biol., November 1, 1998; 18(11): 1730 - 1737. [Abstract] [Full Text] [PDF]