Calcium/Calmodulin-Dependent Protein Kinase II in Cerebrovascular Diseases.

Cerebrovascular disease is the most common life-threatening and debilitating condition that often leads to stroke. The multifunctional calcium/calmodulin-dependent protein kinase II (CaMKII) is a key Ca sensor and an important signaling protein in a variety of biological systems within the brain, heart, and vasculature. In the brain, past stroke-related studies have been mainly focused on the role of CaMKII in ischemic stroke in neurons and established CaMKII as a major mediator of neuronal cell death induced by glutamate excitotoxicity and oxidative stress following ischemic stroke. However, with growing understanding of the importance of neurovascular interactions in cerebrovascular diseases, there are clearly gaps in our understanding of how CaMKII functions in the complex neurovascular biological processes and its contributions to cerebrovascular diseases. Additionally, emerging evidence demonstrates novel regulatory mechanisms of CaMKII and potential roles of the less-studied CaMKII isoforms in the ischemic brain, which has sparked renewed interests in this dynamic kinase family. This review discusses past findings and emerging evidence on CaMKII in several major cerebrovascular dysfunctions including ischemic stroke, hemorrhagic stroke, and vascular dementia, focusing on the unique roles played by CaMKII in the underlying biological processes of neuronal cell death, neuroinflammation, and endothelial barrier dysfunction triggered by stroke. We also highlight exciting new findings, promising therapeutic agents, and future perspectives for CaMKII in cerebrovascular systems.