Up-regulation of parathyroid hormone receptor in cerebral arteries after subarachnoid hemorrhage in monkeys.
OBJECTIVE
Complementary deoxyribonucleic acid array analysis was used to determine whether vasospasm after subarachnoid hemorrhage (SAH) is associated with changes in gene expression.


METHODS
Right SAHs were created in three monkeys, and the right and left middle cerebral arteries were collected 3, 7, or 14 days after SAH. Vasospasm was assessed by angiography performed on Day 0 and at tissue harvest. A complementary deoxyribonucleic acid array containing 5184 genes was used to screen for changes in gene expression by comparing the right and left middle cerebral arteries.


RESULTS
There was significant expression (greater than fivefold expression of messenger ribonucleic acid compared with internal standard control) of 537 genes (10%) in the middle cerebral arteries. One hundred sixty-four genes (31%) did not change significantly, and 373 (69%) were differentially expressed at 3, 7, or 14 days after SAH. These 373 genes changed from 1.2- to 7-fold as compared with control arteries. The most common pattern was a progressive increase with increased time after SAH. The functions of differentially expressed genes included the regulation of gene expression, cell proliferation, inflammation, membrane proteins and receptors, kinases, and phosphatases. There was a marked increase in parathyroid hormone and parathyroid hormone receptor with time after SAH. Immunoblotting demonstrated a significant increase in parathyroid hormone receptor protein.


CONCLUSIONS
The up-regulation of these proteins involved in vascular relaxation suggests that they may play a role in vasospasm. The progressive increase in messenger ribonucleic acids involved in the functions noted suggests that the pathogenesis of cerebral vasospasm involves cell proliferation, inflammation, and possibly smooth muscle phenotype change.
Macdonald
R Loch
RL
Section of Neurosurgery, Department of Surgery, Pritzker School of Medicine and University of Chicago, Chicago, Illinois, USA. lmacdona@surgery.bsd.uchicago.edu
Zhang
Zhen-Du
ZD
Ono
Shigeki
S
Komuro
Taro
T
D000818:Animals; D002533:Cerebral Angiography; D002536:Cerebral Arteries / Q000503:physiopathology*; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D008252:Macaca fascicularis; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018016:Receptors, Parathyroid Hormone / Q000235:genetics*; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation; D020301:Vasospasm, Intracranial / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology
D018076:DNA, Complementary; D020033:Protein Isoforms; D012333:RNA, Messenger; D018016:Receptors, Parathyroid Hormone