Abel to Study Estrogen and Platelet Mitochondria

E. Dale Abel, MD, PhD, has received a two-year, $1.4M NIH grant to explore potential links between estrogen, platelet mitochondria, and increased incidence of thrombosis in females, particularly following estrogen exposure. A successful outcome may identify novel biomarkers that might predict thrombosis risk in this susceptible population.

The mitochondrial protein, OPA1, plays an important role in mitochondrial fusion. Previous epidemiological studies had revealed increased OPA1 in platelets of women but not in men. Also, during pregnancy, increased OPA1 levels in platelets correlate with increased platelet activation. To better understand the molecular mechanisms for this association, Dr. Abel’s laboratory generated mice that lacked OPA1, specifically in platelets. Male OPA1-deficient platelets exhibited overt mitochondrial damage, which was not evident in females. Remarkably, reduced OPA1 in platelets increased the risk of thrombosis in males but decreased the risk of thrombosis in female animals. These phenotypes could be transferred when platelets from one sex were transferred into animals of the opposite sex.

The NIH grant will enable Dr. Abel to pursue mechanisms responsible for this phenomenon and to begin studying this effect in humans, looking for correlations between OPA1 expression in platelets and a history or risk of thrombosis in women. If certain milestones are met by the investigative team, the two-year, R61 grant will transition to an R33 grant, which will provide $2.1M in additional support for three more years. Dr. Abel, Director of the Fraternal Order of Eagles Diabetes Research Center, and his lab members will collaborate with a team led by Dr. Andrew Weyrich at the University of Utah.