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

• Published in: Brain research 2001-08, Vol.910 (1), p.106-115
• Main Authors: Kirsch, Torsten, Wellner, Maren, Luft, Friedrich C, Haller, Hermann, Lippoldt, Andrea
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Arterial hypertension. Arterial hypotension; ATP-Binding Cassette Transporters; Base Sequence; Biological and medical sciences; Blood and lymphatic vessels; Blood-Brain Barrier - genetics; Blood–brain barrier; Cardiology. Vascular system; Causality; Cerebral Arteries - metabolism; Cerebral Arteries - pathology; Cerebral Arteries - physiopathology; DNA, Complementary - genetics; DNA, Complementary - isolation & purification; DNA, Complementary - metabolism; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Endothelium, Vascular - physiopathology; Experimental diseases; Gene Expression Regulation, Developmental - physiology; GTP-Binding Proteins - metabolism; Hypertension; Hypertension - complications; Hypertension - genetics; Hypertension - metabolism; In Situ Hybridization - methods; Medical sciences; Molecular Sequence Data; Peptide Fragments - genetics; Potassium Channels - genetics; Potassium Channels - metabolism; Potassium Channels, Inwardly Rectifying; Rats; Rats, Inbred SHR - abnormalities; Rats, Inbred SHR - genetics; Rats, Inbred SHR - metabolism; Receptors, Drug - genetics; Receptors, Drug - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RGS Proteins - genetics; RGS Proteins - metabolism; RNA, Messenger - metabolism; Sequence Homology, Nucleic Acid; Signal Transduction - physiology; Stroke - genetics; Stroke - metabolism; Stroke - physiopathology; Sulfonylurea Receptors; Suppression subtractive hybridization
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)02670-1

Stroke-prone spontaneously hypertensive rats (SHRSP) are a well-characterized, genetic model for stroke. We showed earlier that the structure and function of the tight junctions in SHRSP blood–brain barrier endothelial cells is disturbed prior to stroke. To investigate the molecular events leading to endothelial dysfunction in SHRSP cerebral capillaries, we carried out suppression subtractive hybridization (SSH) in combination with a cDNA filter screening step. We identified two cDNA fragments that were upregulated in SHRSP, compared to stroke-resistant spontaneously hypertensive rats (SHR), and found open reading frames of 133 and 138 amino acids, respectively. These peptides did not match any known proteins in public databases. A third upregulated SHRSP cDNA fragment was identified as the rat sulfonylurea receptor 2B (SUR2B). We also isolated and cloned the cDNA of the rat homologue for the mouse G-protein signaling 5 (RGS5) regulator. This regulator was downregulated in SHRSP. We used in situ hybridization to show that rat RGS5 is expressed in the brain capillary endothelium and in the choroid plexus. Our findings may lead to the identification of new stroke-related genes.