Migraine-associated mutation leads to cardiac dysfunction
The Na,K-ATPase α2 isoform (encoded by the Atp1a2 gene) is expressed in the heart and is important for normal cardiac function. Mutations in the Atp1a2 gene is associated with Familial Hemiplegic Migraine type 2, a severe type of migraine with aura. Migraine patients have an increased risk of cardiac disease but up until now, the reason for this comorbidity remains unknown. In this study, Christian Staehr et al. show that migraine-associated Atp1a2 mutation leads to disturbances in cardiac metabolism and dysfunction.
A collaboration between groups within Membranes and several other clinical and basic researchers has now resulted in this publication in Journal of the American Heart Association. This comprehensive study provides a detailed mechanistic analysis of cardiovascular function in a mouse strain carrying a migraine-associated mutation in the Atp1a2 gene. The heart structure and function in these mice were studied in vivo using state-of-the-art imaging techniques. The underlying disease mechanism was uncovered by expressional and biochemical measurements followed by analysis of proteomics data.
“In brief, we found that hearts from α2+/G301R mice exhibited left ventricular dilation and reduced left ventricular ejection fraction” Christian Staehr explains. “This was associated with mitochondrial uncoupling and increased oxidative stress. Interestingly, this phenotype was only observered in elderly mice, although younger mice showed similar expressional changes of the Na,K-ATPase”.
This study for the first time suggests the mechanisms responsible for the comorbidity between inherited migraine and cardiovascular disease.
Find the publication here: https://www.ahajournals.org/doi/full/10.1161/JAHA.121.021814