Gene expression and molecular changes in cerebral arteries following subarachnoid hemorrhage in the rat.
OBJECTIVE
The authors investigated early changes in the cerebral arteries of rats that occur after subarachnoid hemorrhage (SAH).


METHODS
Messenger RNA was investigated by performing microarray and quantitative real-time polymerase chain reaction (PCR) analyses, and protein expression was shown by performing immunohistochemical studies. The array data indicated that the initial processes that occur after SAH involve activation of genes involved in angiogenesis, inflammation, and extracellular matrix (ECM) remodeling. The real-time PCR investigation confirmed upregulation of genes that were observed using the microarray to be regulated, including iNOS, MMP13, and cxcl2. The authors also verified the upregulation of previously implicated genes for G-protein-coupled receptors (endothelin B [ETB], angiotensin 1 [AT1], and AT2) and metalloproteinase 9. The results of an immunohistochemical study confirmed that receptor genes that were seen to be regulated produced an increase in protein expression. Double immunostaining of rat cerebral arteries with endothelial cell- or smooth-muscle cell-specific antibodies verified that an increase in ETB, 5-hydrotryptamine (5-HT1B), and 5-HT1D receptor expression occurs in smooth-muscle cells.


CONCLUSIONS
Processes occurring after SAH lead to enhanced arterial contractility and ECM remodeling either directly or through angiogenesis and inflammation. These processes are active via an increase in metalloproteinase expression, the presence of proangiogenic factors, and the expression of proinflammatory genes.
Vikman
Petter
P
Department of Clinical Sciences, Experimental Vascular Research, Lunds Universitet, Lund, Sweden. Petter.vikman@med.lu.se
Beg
Saema
S
Khurana
Tejvir S
TS
Khurana
Tejvir
T
Hansen-Schwartz
Jacob
J
Edvinsson
Lars
L
D000818:Animals; D002536:Cerebral Arteries / Q000737:chemistry* / Q000503:physiopathology; D017364:Collagenases / Q000235:genetics; D005109:Extracellular Matrix / Q000502:physiology; D015870:Gene Expression; D007150:Immunohistochemistry; D008297:Male; D053509:Matrix Metalloproteinase 13; D046228:Microarray Analysis; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000032:analysis; D012701:Serotonin / Q000032:analysis; D013345:Subarachnoid Hemorrhage / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology
D012333:RNA, Messenger; D011985:Receptors, Serotonin; D012701:Serotonin; D052247:Nitric Oxide Synthase Type II; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat