Matrix metalloproteinase-1 and interleukin-17A are associated with previous plaque disruption: a combined proteomics and optical coherence tomography study

Marco Covani; Giampaolo Niccoli; Takayuki Niida; Yoshiyasu Minami; Riccardo Scalamera; Daichi Fujimoto; Sunao Nakamura; Akihiro Nakajima; Kahraman Tanriverdi; Rocco Vergallo; Italo Porto; Iris McNulty; Hang Lee; Taishi Yonetsu; Ik-Kyung Jang

doi:10.1097/MCA.0000000000001593

Matrix metalloproteinase-1 and interleukin-17A are associated with previous plaque disruption: a combined proteomics and optical coherence tomography study

Coron Artery Dis. 2025 Nov 19. doi: 10.1097/MCA.0000000000001593. Online ahead of print.

Authors

Marco Covani^{1

2}, Giampaolo Niccoli², Takayuki Niida¹, Yoshiyasu Minami³, Riccardo Scalamera^{1

4}, Daichi Fujimoto¹, Sunao Nakamura⁵, Akihiro Nakajima⁵, Kahraman Tanriverdi⁶, Rocco Vergallo^{4

7}, Italo Porto^{4

7}, Iris McNulty¹, Hang Lee⁸, Taishi Yonetsu⁹, Ik-Kyung Jang¹

Affiliations

¹ Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
² Cardiology Department, University Hospital of Parma, Parma, Italy.
³ Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
⁴ Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, Genova, Italy.
⁵ Department of Cardiology, Kawasaki Saiwai Hospital, Kawasaki, Japan.
⁶ Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁷ Cardiothoracic and Vascular Department (DICATOV), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, Genova, Italy.
⁸ Biostatistics Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁹ Department of Cardiovascular Medicine, Institute of Science Tokyo, Tokyo, Japan.

PMID: 41257408
DOI: 10.1097/MCA.0000000000001593

Abstract

Objectives: Plaque disruption and subsequent healing are important contributors to coronary plaque progression; however, the biological mechanisms underlying this process remain incompletely understood. Optical coherence tomography (OCT) enables the identification of previously disrupted plaques, referred to as layered plaques. Proteomic analysis can characterize the molecular signature of layered plaques, providing insights into the biology of plaque disruption and healing. Furthermore, layered plaques indicate a more advanced stage of atherosclerotic disease, and their noninvasive identification could enhance patient risk stratification. This study aimed to identify plasma proteins associated with layered plaques at the culprit lesion in patients with stable angina pectoris (SAP).

Methods: Patients undergoing coronary angiography and OCT for SAP, with periprocedural blood sample collection, were enrolled. A proteomic analysis was subsequently performed, assessing 1470 proteins using the Olink explore 1536 reagent kit.

Results: Among 51 patients, OCT identified 31 (60.8%) patients with layered plaques at the culprit lesion. Patients with layered plaques exhibited 2.23- and 2.11-fold higher concentrations of interleukin-17A (IL17A) and matrix metalloproteinase-1 (MMP1), respectively ( P = 0.013 and P < 0.001), compared to those without layered plaques. Multivariable regression models demonstrated that IL17A and MMP1 were associated with layered plaques independent of known predictors (diameter stenosis > 70%, B2/C American College of Cardiology/American Heart Association lesion, and multivessel disease). Adding both proteins to the known predictors significantly improved the area under the curve (AUC) for layered plaque detection (AUC 0.831 vs. 0.581; P = 0.007).

Conclusion: In patients with SAP, IL17A, and MMP1 were independently associated with layered plaques identified by OCT.

Keywords: acute coronary syndromes; healed plaque; layered plaque; optical coherence tomography; plaque disruption; stable angina pectoris.