Premenopausal women have a much lower risk of heart disease compared to men of similar age. But after menopause, the heart disease risk for women rises quickly to equal the risk for men. A recent study discovered a new mechanism by which estrogen protects blood vessels. Estrogen prevents white blood cells, called polymorphonuclear leukocytes or PMNs from sticking to the lining of blood vessels and releasing substances that injure blood vessels.
Estrogen protects blood vessels
When the body is injured or invaded by bacteria or other microbes, PMNs, which make up about 60 percent of all white blood cells, are the first line of defense. PMNs rush immediately to the site of injury or infection. These white blood cells have a limited lifespan and are loaded with digestive enzymes and toxins. When PMNs become activated, prepared to fight microbes or scavenge dead tissue, they become sticky, adhere to blood vessels, and cause damage by releasing their enzymes and toxins. Researchers at the University of London found that estrogen could prevent PMNs from sticking to blood vessels and causing injury. In the absence of estrogen, the vascular injuries could lead to heart disease. The researchers found that estrogen made the blood cells non-sticky by moving a protein, called annexin-1, from the inside of the white blood cells to the outside surface, where it acted like a Teflon coating. When the researchers examined PMNs from blood samples of premenopausal women and from blood samples of men for annexin-1, they found much higher amounts of annexin-1 on the PMNs of premenopausal women than on the PMNs of men. The amount of annexin-1 on the surface of PMNs also paralleled the blood level of estrogen during the menstrual cycle.
Birth control pills and HRT
Although estrogen has beneficial effects on cardiovascular health, oral intake of estrogen – as with birth control pills and hormone replacement therapy (HRT) – has no effect or even adverse effects on the vasculature and the heart. Researchers believe that the adverse cardiovascular effects are caused by estrogen’s action on the liver. Estrogen stimulates the production of clotting proteins by the liver and so encourages the formation of blood clots, called thrombi, in the lower legs or other areas. These clots can break loose and travel to the heart or brain and cause heart attacks or strokes. Studies suggest that some women are more prone to blood clotting and that external administration of estrogen, such as with a skin patch, does not stimulate the liver to make more blood clotting proteins and may prevent adverse cardiovascular effects.
Implications
Until this study, researchers had no clue as to why estrogen was cardio-protective in premenopausal women. The newly discovered mechanism, preventing white blood cells from sticking to and damaging the vasculature, could account for all or most of the cardio-protective effects by estrogen. The authors of the study conclude: “We unveil a novel AnxA1-dependent mechanism behind the inhibitory properties of estrogen on PMN activation, describing a novel phenotype with conceivable impact on the vasculoprotective effects of the hormone” (Nadkarni, S. et al). Because oral estrogen as in HRT may have all kinds of adverse effects, this newly discovered mechanism of estrogen action may lead to the development of new treatments to improve the cardiovascular health of postmenopausal women.
Sources
Nadkami, S. et al. Activation of the Annexin A1 Pathway Underlies the Protective Effects Exerted by Estrogen in Polymorphonuclear Leukocytes. Arteroscler. Thromb. Vasc. Biol. (2011), DOI: 10.1161/ATVBAHA.111.235176
http://www.sciencedaily.com/releases/2011/08/110811181716.htm
http://www.sciencedaily.com/releases/2009/03/090326134024.htm
http://www.annals.org/content/136/9/I42.full