Circulating and tissue matricellular RNA and protein expression in calcific aortic valve disease

Research output: Contribution to journalArticle

Authors

  • Alexander P. Kossar
  • Wanda Anselmo
  • Juan B. Grau
  • Yichuan Liu
  • Aeron Small
  • Samuel L. Carter
  • Lisa Salvador
  • Lei Zhao
  • Mary Ellen Cvijic
  • Zhuyin Li
  • Melissa Yarde
  • Nancy Rioux
  • Daniel J. Rader
  • Robert J. Levy
  • Giovanni Ferrari

External Institution(s)

  • Columbia University
  • University of Pennsylvania
  • University of Ottawa
  • Bristol-Myers Squibb
  • Valley Heart Center

Details

Original languageEnglish (US)
Pages (from-to)191-199
Number of pages9
JournalPhysiological genomics
Volume52
Issue number4
StatusPublished - Apr 2020
Peer-reviewedYes

Abstract

Aortic valve sclerosis is a highly prevalent, poorly characterized asymptomatic manifestation of calcific aortic valve disease and may represent a therapeutic target for disease mitigation. Human aortic valve cusps and blood were obtained from 333 patients undergoing cardiac surgery (n = 236 for severe aortic stenosis, n = 35 for asymptomatic aortic valve sclerosis, n = 62 for no valvular disease), and a multiplex assay was used to evaluate protein expression across the spectrum of calcific aortic valve disease. A subset of six valvular tissue samples (n = 3 for asymptomatic aortic valve sclerosis, n = 3 for severe aortic stenosis) was used to create RNA sequencing profiles, which were subsequently organized into clinically relevant gene modules. RNA sequencing identified 182 protein-encoding, differentially expressed genes in aortic valve sclerosis vs. aortic stenosis; 85% and 89% of expressed genes overlapped in aortic stenosis and aortic valve sclerosis, respectively, which decreased to 55% and 84% when we targeted highly expressed genes. Bioinformatic analyses identified six differentially expressed genes encoding key extracellular matrix regulators: TBHS2, SPARC, COL1A2, COL1A1, SPP1, and CTGF. Differential expression of key circulating biomarkers of extracellular matrix reorganization was observed in control vs. aortic valve sclerosis (osteopontin), control vs. aortic stenosis (osteoprotegerin), and aortic valve sclerosis vs. aortic stenosis groups (MMP-2), which corresponded to valvular mRNA expression. We demonstrate distinct mRNA and protein expression underlying aortic valve sclerosis and aortic stenosis. We anticipate that extracellular matrix regulators can serve as circulating biomarkers of early calcific aortic valve disease and as novel targets for early disease mitigation, pending prospective clinical investigations.

    Research areas

  • Aortic stenosis, Aortic valve sclerosis, Calcific aortic valve disease, Genomics, Proteomics

Citation formats

APA

Kossar, A. P., Anselmo, W., Grau, J. B., Liu, Y., Small, A., Carter, S. L., ... Ferrari, G. (2020). Circulating and tissue matricellular RNA and protein expression in calcific aortic valve disease. Physiological genomics, 52(4), 191-199. https://doi.org/10.1152/physiolgenomics.00104.2019

Harvard

Kossar, AP, Anselmo, W, Grau, JB, Liu, Y, Small, A, Carter, SL, Salvador, L, Zhao, L, Cvijic, ME, Li, Z, Yarde, M, Rioux, N, Rader, DJ, Levy, RJ & Ferrari, G 2020, 'Circulating and tissue matricellular RNA and protein expression in calcific aortic valve disease', Physiological genomics, vol. 52, no. 4, pp. 191-199. https://doi.org/10.1152/physiolgenomics.00104.2019