Brain endothelium: a nexus for cerebral small vessel disease.

Brain endothelial cells (BECs) have unique roles in controlling cerebral blood flow (CBF) and as a cornerstone of the blood-brain barrier (BBB). Graph: Figure 1 The BRENDA network will define mechanisms linking risk genes for cerebral small vessel disease and stroke to brain endothelial cell dysfunction and brain injury, applying cutting edge technology to novel disease models, including human inducible pluripotent stem cell-based models of the blood-brain barrier and neurovascular unit (Aim 1); test whether genetic predisposition synergizes with hypertension to augment brain endothelial cell dysfunction and brain injury (Aim 2, "two-hit" model); and determine whether brain endothelial cell heterogeneity underlies differences in brain injury across regions (Aim 3). Genome-wide association studies[8] implicate BEC dysfunction in disease initiation and propagation.[5] For instance, common variants of I FOXF2 i are associated with small vessel stroke and white matter lesions (WMLs). [Extracted from the article]