TY - JOUR
T1 - Cochlear pericyte responses to acoustic trauma and the involvement of hypoxia-inducible factor-1α and vascular endothelial growth factor
AU - Shi, Xiaorui
N1 - Funding Information:
Supported by the National Institute of Deafness and Other Communications Disorders (grants R01 DC000141, R03 DC008888-02, and P30 DC005983 ).
PY - 2009/5
Y1 - 2009/5
N2 - This study explored the effect of acoustic trauma on cochlear pericytes. Transmission electron microscopy revealed that pericytes on capillaries of the stria vascularis were closely associated with the endothelium in both control guinea pigs and mice. Pericyte foot processes were tightly positioned adjacent to endothelial cells. Exposure to wide-band noise at a level of 120 dB for 3 hours per day for 2 consecutive days produced a significant hearing threshold shift and structurally damaged blood vessels in the stria vascularis. Additionally, the serum protein, IgG, was observed to leak from capillaries of the stria vascularis, and pericytes lost their tight association with endothelial cells. Levels of the pericyte structural protein, desmin, substantially increased after noise exposure in both guinea pigs and mice with a corresponding increase in pericyte coverage of vessels. Increased expression levels of desmin were associated with the induction of hypoxia inducible factor (HIF)-1α and the up-regulation of vascular endothelial growth factor (VEGF). Inhibition of HIF-1α activity caused a decrease in VEGF expression levels in stria vascularis vessels. Blockade of VEGF activity with SU1498, a VEGF receptor inhibitor, significantly attenuated the expression of desmin in pericytes. These data demonstrate that cochlear pericytes are markedly affected by acoustic trauma and display an abnormal morphology. HIF-1α activation and VEGF up-regulation are important factors for the alteration of the pericyte structural protein desmin.
AB - This study explored the effect of acoustic trauma on cochlear pericytes. Transmission electron microscopy revealed that pericytes on capillaries of the stria vascularis were closely associated with the endothelium in both control guinea pigs and mice. Pericyte foot processes were tightly positioned adjacent to endothelial cells. Exposure to wide-band noise at a level of 120 dB for 3 hours per day for 2 consecutive days produced a significant hearing threshold shift and structurally damaged blood vessels in the stria vascularis. Additionally, the serum protein, IgG, was observed to leak from capillaries of the stria vascularis, and pericytes lost their tight association with endothelial cells. Levels of the pericyte structural protein, desmin, substantially increased after noise exposure in both guinea pigs and mice with a corresponding increase in pericyte coverage of vessels. Increased expression levels of desmin were associated with the induction of hypoxia inducible factor (HIF)-1α and the up-regulation of vascular endothelial growth factor (VEGF). Inhibition of HIF-1α activity caused a decrease in VEGF expression levels in stria vascularis vessels. Blockade of VEGF activity with SU1498, a VEGF receptor inhibitor, significantly attenuated the expression of desmin in pericytes. These data demonstrate that cochlear pericytes are markedly affected by acoustic trauma and display an abnormal morphology. HIF-1α activation and VEGF up-regulation are important factors for the alteration of the pericyte structural protein desmin.
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U2 - 10.2353/ajpath.2009.080739
DO - 10.2353/ajpath.2009.080739
M3 - Article
C2 - 19349367
AN - SCOPUS:65649092119
SN - 0002-9440
VL - 174
SP - 1692
EP - 1704
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 5
ER -