Tau Protein in Human Brain Vascular Smooth Muscle

Abstract

BackgroundIschemic stroke is a leading cause of long‐term disability and death worldwide. Thickening of the vascular wall and the reduction of lumen increase the incidence of ischemic stroke. Thus, therapeutic strategies targeting brain vascular narrowing should reduce the mortality and morbidity associated with ischemic stroke. Vascular smooth muscle cell (SMC) proliferation contributes to the development of vascular narrowing, however, cell signaling mechanisms of brain vascular SMC proliferation has not been defined. Tau is a microtubule‐associated protein indicated in various neurological pathologies, including Alzheimer’s disease. Although Tau protein is known to be expressed in neuronal cells, the role of Tau in brain vasculature is unknown. The present study tested the hypothesis that Tau is expressed in brain vascular SMCs.Methods & ResultsImmunohistochemistry of postmortem brain tissues from human patients died of ischemic stroke demonstrated the expression of Tau protein in the vascular smooth muscle media layer. Western blotting of cell lysates from cultured human brain vascular SMCs revealed the occurrence of a Tau isoform with a molecular weight of ~45 kD that was knocked down by Tau siRNA. Treatment of cells with a potent mitogen of SMCs, platelet‐derived growth factor (PDGF), promoted the phosphorylation of Tau at Thr181, but not, Ser198, Ser199, Ser202, Thr205, Thr212, Ser214, Ser356, Ser404, or Ser422. A Tau protein aggregation inhibitor, methylene blue, inhibited human brain vascular SMC growth.ConclusionsThis is the first demonstration that Tau protein is expressed in any kind of vascular SMCs. Moreover, results showing that PDGF causes the phosphorylation of Tau at a specific amino acid and a Tau aggregation inhibitor suppresses cell growth suggest that Tau may play a role in cell growth signaling in brain vascular SMCs.Support or Funding InformationSupported by NIH