Author + information
- Nick E.J. West, MDa,
- Joseph P. Corrigan, MEngb,
- Richard H.G. Owen, PhDb,
- Stephen P. Hoole, DMa,
- Adam J. Brown, PhDa,
- Stephen Blatcher, PhDb and
- Andrew C. Newby, PhDc,∗ ()
- aPapworth Hospital National Health Service Foundation Trust, Cambridge, United Kingdom
- bPlaqueTec, Ltd., Cambridge, United Kingdom
- cBristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
- ↵∗Address for correspondence:
Prof. Andrew C. Newby, British Heart Foundation, Research and Teaching Floor Level 7, Bristol Royal Infirmary, Upper Maudlin Street, Bristol, BS2 8HW, United Kingdom.
• Deployment of the Liquid Biopsy System into normal coronary arteries and its use to take 4 simultaneous blood samples at equal spaces along a 10-cm length was shown to be feasible and safe in patients undergoing angioplasty. No gradients of the 92 biomolecules chosen for multiplexed analysis were observed.
• By contrast, stable and disrupted plaques showed biomolecule gradients along the sampling length, which implied that substances were being released from plaques into the boundary layer and flowing blood that was coursing over them. Gradients of molecules likely to be derived from the endothelium overlying plaques, especially the oxidized LDL receptor (OLR1; also known as LOX-1) and inflammatory mediators, were detected, consistent with the inflammatory status of endothelium previously defined by ex vivo and postmortem studies.
• After angioplasty, some molecular gradients persisted, but release of additional substances was observed, perhaps most interestingly, matrix metalloproteinase-12, which had been localized previously to the core of vulnerable plaques and associated with subsequent unstable presentation.
• These experiments establish the feasibility and potential of the Liquid Biopsy System. This new methodology is flexible enough to be used in conjunction with high-content analyses for the definition of prognostic biomarkers or biomarker combinations and for the development of surrogate endpoints in clinical intervention studies aimed at reducing plaque vulnerability and preventing acute coronary syndromes.
A percutaneous catheter device, the Liquid Biopsy System, was developed to sample the unstirred boundary layer of blood upstream and downstream of intact and disrupted human coronary atherosclerotic plaques. Using multiplexed proximity extension assays, release of 20 biomolecules was simultaneously detected in samples taken across plaques before balloon angioplasty, including the soluble form of the endothelial lectin-like oxidized LDL receptor. Additional biomolecules, including matrix metalloproteinase-12, were released after plaque disruption with angioplasty. These experiments demonstrate the power of the Liquid Biopsy System to yield new scientific insights and its ultimate potential to generate new biomarkers and surrogate endpoints for clinical trials.
Supported by PlaqueTec, Ltd. Dr. Newby was supported by grant CH95001 from the British Heart Foundation. Drs. Corrigan, Owen, and Blatcher are employees of PlaqueTec, Ltd. Drs. West, Hoole, Brown, and Newby are consultants for PlaqueTec, Ltd.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received March 11, 2017.
- Revision received July 4, 2017.
- Accepted July 6, 2017.
- 2017 The Authors