Altered gene expression in cerebral capillaries of stroke-prone spontaneously hypertensive rats

Stroke-prone spontaneously hypertensive rats (SHRSP) are a well-characteriz ed, genetic model for stroke. We showed earlier that the structure and func tion of the tight junctions in SHRSP blood-brain barrier endothelial cells is disturbed prior to stroke. To investigate the molecular events leading t o endothelial dysfunction in SHRSP cerebral capillaries, we carried out sup pression subtractive hybridization (SSH) in combination with a cDNA filter screening step. We identified two cDNA fragments that were upregulated in S HRSP, compared to stroke-resistant spontaneously hypertensive rats (SHR), a nd found open reading frames of 133 and 138 amino acids, respectively. Thes e peptides did not match any known proteins in public databases. A third up regulated SHRSP cDNA fragment was identified as the rat sulfonylurea recept or 2B (SUR2B). We also isolated and cloned the cDNA of the rat homologate f or the mouse G-protein signaling 5 (RGS5) regulator. This regulator was dow nregulated in SHRSP. We used in situ hybridization to show that rat RGS5 is expressed in the brain capillary endothelium and in the choroid plexus. Ou r findings may lead to the identification of new stroke-related genes. (C) 2001 Elsevier Science B.V. All rights reserved.