Article Text

Download PDFPDF
Heart-Brain Signaling in Patent Foramen Ovale–Related Stroke
  1. Mary F. Lopez, PhD*,
  2. David A. Sarracino, PhD*,
  3. Maryann Vogelsang, PhD*,
  4. Jennifer N. Sutton, PhD*,
  5. Michael Athanas, PhD*,
  6. Bryan Krastins, MBA*,
  7. Alejandra Garces, MS*,
  8. Amol Prakash, PhD*,
  9. Scott Peterman, PhD*,
  10. Zareh Demirjian, MD,
  11. Ignacio Inglessis-Azuaje, MD,
  12. Kathleen Feeney, MD,
  13. Mikaela Elia, MD,
  14. David McMullin, MD,
  15. G. William Dec, MD,
  16. Igor Palacios, MD,
  17. Eng H. Lo, MD,
  18. Ferdinand Buonanno, MD,
  19. MingMing Ning, MD
  1. From the *Thermo Fisher Scientific BRIMS, Cambridge; and †Clinical Proteomics Research Center and Cardio-Neurology Clinic, Department ofNeurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
  1. Received September 28, 2012.
  2. Accepted for publication September 28, 2012.
  3. Reprints: Mary F. Lopez, PhD, BRIMS, Thermo Fisher Scientific, 790 Memorial Dr, Cambridge, MA 02139. E-mail: mary.lopez{at}; or MingMing Ning, MD, Clinical Proteomics Research Center, Massachusetts General Hospital/Harvard Medical School, 15 Parkman St, ACC 720; Boston, MA 02114. E-mail: ning{at}
  4. This work was supported by the NIH/NINDS: R01 NS067139 (M.M.N.) and P01-NS55104 (E.H.L.). The symposium was supported in part by a grant from the National Center for Research Resources (R13 RR023236).
  5. Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions ofthis article on the journal’s Web site (

Differential Plasma Proteomic Expression Patterns Revealed With a 2-Pass Liquid Chromatography–Tandem Mass Spectrometry Discovery Workflow


Patent foramen ovale (PFO) is highly prevalent and associated with more than 150,000 strokes per year. Traditionally, it is thought that PFOs facilitate strokes by allowing venous clots to travel directly to the brain. However, only a small portion of PFO stroke patients have a known tendency to form blood clots, and the optimal treatment for this multiorgan disease is unclear. Therefore, mapping the changes in systemic circulation of PFO-related stroke is crucial in understanding the pathophysiology to individualize the best clinical treatment for each patient. We initiated a study using a novel quantitative, 2-pass discovery workflow using high-resolution liquid chromatography–mass spectrometry/mass spectrometry coupled with label-free analysis to track protein expression in PFO patients before and after endovascular closure of the PFO. Using this approach, we were able to demonstrate quantitative differences in protein expression between both PFO-related and non–PFO-related ischemic stroke groups as well as before and after PFO closure. As an initial step in understanding the molecular landscape of PFO-related physiology, our methods have yielded biologically relevant information on the synergistic and functional redundancy of various cell-signaling molecules with respect to PFO circulatory physiology. The resulting protein expression patterns were related to canonical pathways including prothrombin activation, atherosclerosis signaling, acute-phase response, LXR/RXR activation, and coagulation system.

In particular, after PFO closure, numerous proteins demonstrated reduced expression in stroke-related canonical pathways such as acute inflammatory response and coagulation signaling. These findings demonstrate the feasibility and robustness of using a proteomic approach for biomarker discovery to help gauge therapeutic efficacy in stroke.

Key Words
  • patent foramen ovale
  • PFO
  • proteomics
  • biomarker
  • discovery
  • stroke
  • cerebrovascular disease
  • ischemic stroke
  • mass spectrometry

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.