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Protease inhibitor 15, a candidate gene for abdominal aortic internal elastic lamina ruptures in the rat

Authors

  • S. Falak
  • S. Schafer
  • A. Baud
  • O. Hummel
  • H. Schulz
  • D. Gauguier
  • N. Hubner
  • M. Osborne-Pellegrin

Journal

  • Physiological Genomics

Citation

  • Physiol Genomics 46 (12): 418-428

Abstract

  • The inbred Brown Norway (BN) rat develops spontaneous ruptures of the internal elastic lamina (RIEL) of the abdominal aorta (AA) and iliac arteries. Prior studies with crosses of the BN/Orl RJ (susceptible) and LOU/M (resistant) showed the presence of a significant QTL on chromosome 5 and the production of congenic rats proved the involvement of this locus. In this study, we further dissected the above-mentioned QTL by creating a new panel of LOU.BN(chr5) congenic and sub-congenic lines and reduced the locus to 5.2 Mb. Then 1002 HS rats were studied, whose phenotyping revealed a low prevalence and high variability for RIEL. High resolution mapping in the HS panel detected the major locus on chromosome 5 (log P>35) and refined it to 1.4Mb. Subsequently, RNA-seq analysis on AA of BN, congenics and LOU revealed expression differences for only protease inhibitor15 (Pi15) gene and a putative long intergenic noncoding RNA (lincRNA) within the linkage region. The high abundance of lincRNA with respect to reduced Pi15 expression, in conjunction with exertion of longitudinal strain, may be related to RIEL, indicating the potential importance of proteases in biological processes related to defective aortic IEL structure. Similar mechanisms may be involved in aneurysm initiation in the human AA.


DOI

doi:10.1152/physiolgenomics.00004.2014