su-1498 and Hearing-Loss--Sensorineural

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)-1alpha and the up-regulation of vascular endothelial growth factor (VEGF). Inhibition of HIF-1alpha 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-1alpha activation and VEGF up-regulation are important factors for the alteration of the pericyte structural protein desmin.

Topics: Animals; Blotting, Western; Butyrates; Cell Hypoxia; Cinnamates; Cochlea; Desmin; Female; Guinea Pigs; Hearing Loss, Noise-Induced; Hearing Loss, Sensorineural; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoenzyme Techniques; Male; Mice; Mice, Inbred C57BL; Pericytes; Protein Transport; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factors