For the 1/3 of women who are menopausal, the risk of heart disease is much higher compared to pre-menopause. Unfortunately less is known about heart disease in women and there are no sex-specific therapies. Dr Ed O’Brien is a cardiologist and his research laboratory discovered a protein that acts as a “foot soldier” for estrogen. Estrogen levels plummet with menopause when ovarian function ceases – typically between 45 and 55 years – and are thought to be “protective” against the development of heart disease.

While estrogen “replacement” therapies for post-menopausal women are used to releive some symptoms of menopause (e.g., hot flashes) there are concerns about their safety. Indeed, a recent meta-analysis from Oxford University, published in the Lancet on August 29, 2019, suggests that the risk of breast cancer with hormone replacement therapy during menopause is higher than previously understood.

Hence, there is a need to look for new alternatives to HRT for post-menopausal women – and the O’Brien lab has developed a new immunotherapy involving Heat Shock Protein 27 (HSP27) that may be very important in reducing cholesterol levels and hardening of the arteries (“atherosclerosis”).

In a Late Breaking Basic and Translational Science presentation at the European Society of Cardiology Congress in Paris, Dr. O’Brien reported that vaccination with HSP27 is superior to Estrogen therapy in a mouse model of menopause (that involves surgical removal of the ovaries).

Briefly, Estrogen was found to dramatically increase levels of PCSK9 – a negative regulator of cholesterol metabolism. In contrast, HSP27 (or the mouse equivalent, HSP25) had no effect on PCSK9 expression levels, but could neutralize the bad effect of Estrogens on PCSK9.

Conversely, HSP25 increased the expression levels of the receptor (LDL-R) that removes low density lipoprotein (“bad”) cholesterol from the circulation, and reduces the development of hardening of the arteries.

Taken together, these data provide a new opportunity for the development of a therapy for post-menopausal atherosclerosis that involves a simple vaccination technique. In separate studies, this HSP27 vaccination strategy also reduces inflammation, and is effective in male as well as female mice. Studies are ongoing, and are aimed at translating these research developments to the clinic.

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