Proteomic analysis of aortic smooth muscle cell secretions reveals an association of myosin heavy chain 11 with abdominal aortic aneurysm

Am J Physiol Heart Circ Physiol. 2018 Oct 1;315(4):H1012-H1018. doi: 10.1152/ajpheart.00329.2018. Epub 2018 Jul 13.

Abstract

Abdominal aortic aneurysm (AAA) is a life-threatening disease, and no disease-specific circulating biomarkers for AAA screening are currently available. We have identified a smooth muscle cell (SMC)-specific biomarker for AAA. We cultured aneurysmal tunica media that were collected from eight patients undergoing elective open-repair surgeries. Secreted proteins in culture medium were subjected to liquid chromatography/tandem mass spectrometry. Myosin heavy chain 11 (myosin-11) was identified as a SMC-specific protein in the tunica media-derived secretions of all patients. We then examined myosin-11 protein concentrations by ELISA in plasma samples from patients with AAA ( n = 35) and age-matched healthy control subjects ( n = 34). Circulating myosin-11 levels were significantly higher in patients with AAA than control subjects. The area under the receiver-operating characteristic curve (AUC) of myosin-11 was 0.77, with a specificity of 65% at a sensitivity of 91%. Multivariate logistic regression analysis showed a significant association between the myosin-11 level and presence of AAA. When the myosin-11 level was combined with hypertension, it improved the prediction of AAA (AUC 0.88) more than hypertension per se. We then investigated the correlation between aortic diameter and circulating myosin-11 levels using AAA serum samples from patients undergoing endovascular aneurysm repair ( n = 20). Circulating myosin-11 levels were significantly correlated with maximum aortic diameter. Furthermore, changes in myosin-11 concentrations from the baseline 12 mo after endovascular aneurysm repair were associated with those in aortic diameter. These data suggest that circulating levels of myosin-11, which is a SMC-specific myosin isoform, may be useful as a biomarker for AAA. NEW & NOTEWORTHY Extensive studies have revealed that inflammation- or proteolysis-related proteins are proposed as biomarkers for abdominal aortic aneurysm (AAA). Changes in these protein concentrations are not specific for smooth muscle, which is a major part of AAA pathologies. Hence, no disease-specific circulating markers for AAA are currently available. We found, using secretome-based proteomic analysis on human AAA tunica media, that myosin heavy chain 11 was associated with AAA. Circulating myosin heavy chain 11 may be a new tissue-specific AAA marker.

Keywords: abdominal aortic aneurysm; biomarkers; myosin heavy chain; smooth muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aorta, Abdominal / metabolism
  • Aorta, Abdominal / pathology
  • Aortic Aneurysm, Abdominal / blood
  • Aortic Aneurysm, Abdominal / metabolism*
  • Aortic Aneurysm, Abdominal / pathology
  • Biomarkers / blood
  • Case-Control Studies
  • Chromatography, Liquid
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / pathology
  • Myosin Heavy Chains / blood
  • Myosin Heavy Chains / metabolism*
  • Proteomics / methods*
  • Tandem Mass Spectrometry
  • Tissue Culture Techniques

Substances

  • Biomarkers
  • MYH11 protein, human
  • Myosin Heavy Chains