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Selective oestrogen targeting to protect the heart and blood vessels
Diseases of the blood vessels and heart, which are known as cardiovascular diseases, are the most common causes of death in the US. They include heart failure and atherosclerosis (also known as hardening of the arteries), which is a common cause of heart attack and stroke. The hormone oestrogen is thought to have cardiovascular protective effects. However, hormone therapy with oestrogen alone increases the risk of uterine cancer in women. By dissecting the different pathways by which oestrogen signals to cells in mice, a team of researchers, led by Philip Shaul, at the University of Texas Southwestern Medical Centre, Dallas, has now determined that it might be possible to selectively harness the cardiovascular benefits of oestrogen.
Specifically, the team found that an oestrogen-dendrimer conjugate that activated only the subset of oestrogen receptors (the proteins to which oestrogen binds to mediate its effects) that reside at the cell membrane, and not those in the nucleus, promoted cardiovascular protection in mice and did not stimulate either uterine enlargement or breast cancer xenograft growth. In an accompanying commentary, Michael Mendelsohn and Richard Karas, at Tufts Medical Centre, Boston, suggest that, 'translation of these findings into clinically relevant therapeutic interventions is a logical next goal.' However, they caution that there is a long road ahead to realising this goal.
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