Hhip haploinsufficiency sensitizes mice to age-related emphysema

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Abstract
Significance: Genome-wide association studies (GWAS) have been very successful in discovering genetic loci associated with complex traits. However, only few studies applied murine models to investigate how GWAS genes contribute to human lung diseases. Motivated by GWAS linking Hedgehog interacting protein ( HHIP ) to emphysema and impairments in lung function, this study demonstrated that Hhip +/− mice developed spontaneous emphysema and lung function impairment over time. Moreover, emphysema, associated with increased oxidative stress in Hhip +/− lungs, was prevented by treating the mice with the antioxidant, N -acetyl cysteine (NAC). This post-GWAS functional study connects aging-related diseases, molecular mechanisms, and potential therapy in a genetic haploinsufficient murine model, which may lead to improvements in understanding pathophysiologic concepts of alveolar loss related to aging.
Funding Information
  • NIH (R01 HL075478)
  • NIH (P01 HL105339)
  • NIH (R01HL111759)
  • NIH (R01HL127200)
  • NIH (R33 HL120794)
  • NIH (R01 AI111475-01)
  • NIH (R21 HL111835)

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