Shear Stress and Aortic Strain Associations With Biomarkers of Ascending Thoracic Aortic Aneurysm

Salvatore Pasta, Valentina Agnese, Alessia Gallo, Federica Cosentino, Marzio Di Giuseppe, Giovanni Gentile, Giuseppe M Raffa, Joseph F Maalouf, Hector I Michelena, Diego Bellavia, Pier Giulio Conaldi, Michele Pilato

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: This study aims to investigate the association of wall shear stress (WSS) and aortic strain with circulating biomarkers including matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinase (TIMP), and exosomal level of microRNA (miRNA) in ascending aortic aneurysms of patients with bicuspid or tricuspid aortic valve.

METHODS: A total of 76 variables from 125 patients with ascending aortic aneurysms were collected from (1) blood plasma to measure plasma levels of miRNAs and protein activity; (2) computational flow analysis to estimate peak systolic WSS and time-average WSS (TAWSS); and (3) imaging analysis of computed tomography angiography to determine aortic wall strain. Principal component analysis followed by logistic regression allowed the development of a predictive model of aortic surgery by combining biomechanical descriptors and biomarkers.

RESULTS: The protein activity of MMP-1, TIMP-1, and MMP-2 was positively correlated to the systolic WSS and TAWSS observed in the proximal ascending aorta (eg, R = 0.52, P < .001, for MMP-1 with TAWSS) where local maxima of WSS were found. For bicuspid patients, aortic wall strain was associated with miR-26a (R = 0.55, P = .041) and miR-320a (R = 0.69, P < .001), which shows a significant difference between bicuspid and tricuspid patients. Receiver-operating characteristics curves revealed that the combination of WSS, MMP-1, TIMP-1, and MMP-12 is predictive of aortic surgery (area under the curve 0.898).

CONCLUSIONS: Increased flow-based and structural descriptors of ascending aortic aneurysms are associated with high levels of circulating biomarkers, implicating adverse vascular remodeling in the dilated aorta by mechanotransduction. A combination of shear stress and circulating biomarkers has the potential to improve the decision-making process for ascending aortic aneurysms to a highly individualized level.

Original languageEnglish
Pages (from-to)1595-1604
Number of pages10
JournalAnnals of Thoracic Surgery
Volume110
Issue number5
DOIs
Publication statusPublished - Nov 2020

Keywords

  • Adult
  • Aged
  • Aorta/physiopathology
  • Aortic Aneurysm, Thoracic/blood
  • Aortic Valve/abnormalities
  • Bicuspid Aortic Valve Disease/surgery
  • Biomarkers
  • Female
  • Humans
  • Logistic Models
  • Male
  • Matrix Metalloproteinase 1/blood
  • Matrix Metalloproteinase 12/blood
  • Mechanotransduction, Cellular
  • MicroRNAs/blood
  • Middle Aged
  • Stress, Mechanical
  • Tissue Inhibitor of Metalloproteinase-1/blood
  • Vascular Remodeling

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