Fatty Acid Methylation from the Heart to the Brain

Kevin, Hung Wen Lin, PhD


Assistant Professor, Department of Neurology, Director of the Stroke Center for Research, Louisiana State University Health Science Center, Shreveport, LA



Cardiopulmonary arrest is a major cause of death and disability in the US. Cardiac arrest affects up to 325,000 people each year with only a 10% survival rate. The whole-body ischemia following cardiac arrest results in subsequent brain damage resulting in neurological deficits. Our long-term goal is to decrease brain damage by reviving cerebral blood flow and subsequent neurological deficits associated with cardiac arrest. Therefore, it is important to understand the mechanism(s) underlying cardiac arrest -induced brain injury. The importance of identifying regulatory factors that influence cerebral blood flow autoregulation and innovative neuroprotective agents in the context of cardiac arrest is paramount to change the outcomes following cardiac arrest. We previously discovered that PAME [derived from the superior cervical ganglion (SCG)] is a novel vasodilator/neuroprotective agent enhanced in the presence of arginine derivatives. Here, we show that methylation of palmitic acid (i.e. palmitic acid methyl ester, PAME) but not palmitic acid (PA), is necessary to enhance cerebral blood flow, neuroprotection and cognitive function after cardiac arrest. Methylation, via arginine derivatives, can be regulated by protein arginine methyltransferases (PRMT1-10), which are involved in histone methylation and other post-translational modifications. PRMT8 is localized in the central nervous system with no known function to date. Our data suggest that PRMT8 can methylate PA to form PAME. Additionally, PRMT8 is important to prevent behavioral deficits caused by cardiac arrest-induced hypoperfusion.