Hormone replacement therapy and inflammation: interactions in cardiovascular disease.
Inflammation plays a central role in the pathogenesis of many forms of vascular disease, including atherosclerosis. Atherogenesis begins with endothelial damage, and the damaged endothelium expresses adhesion molecules, chemokines, and proinflammatory cytokines that direct atherosclerotic plaque formation and spill into the circulation as biomarkers of atherosclerotic disease risk. Menopausal hormone therapy, including a variety of estrogen preparations with or without a progestin, has negative modulatory effects on most of these soluble inflammatory markers, including E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha, inconsistent effects on interleukin-6, and stimulatory effects on transforming growth factor-beta, a vasoprotective cytokine. In contrast, C-reactive protein, a circulating proinflammatory cytokine produced in both liver and atherosclerotic arteries, increases in response to oral conjugated estrogens but not to transdermal estrogen. Although C-reactive protein is clearly linked to increased cardiovascular disease risk in women, the hormone-induced rise in this biomarker is not associated with increased risk and may be related to a first-pass effect of C-reactive protein production in the liver after oral estrogen absorption. Many important questions about the effects of ovarian hormones on vascular inflammation and the pathogenesis of vascular disease cannot be answered in human subjects. Insights from fundamental mechanistic studies in animal models are needed to delineate the cellular/molecular events that determine whether these hormones protect or injure blood vessels.
Miller
Andrew P
AP
Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, 1047 Zeigler Research Bldg, 703 19th St South, Birmingham, AL 35294-0007, USA. apmiller@uab.edu
Chen
Yiu-Fai
YF
Xing
Dongqi
D
Feng
Wenguang
W
Oparil
Suzanne
S
D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D002318:Cardiovascular Diseases / Q000276:immunology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D020249:Hormone Replacement Therapy; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000175:diagnosis; D008297:Male; D051381:Rats; D012307:Risk Factors
D015415:Biomarkers; D012739:Gonadal Steroid Hormones