Endothelial Shear Stress Metrics Associate With Proinflammatory Pathways at the Culprit Site of Coronary Erosion.

Low endothelial shear stress (ESS) and associated adverse biomechanical features stimulate inflammation, contribute to atherogenesis, and predispose to coronary plaque disruption. The mechanistic links between adverse flow-related hemodynamics and inflammatory mediators implicated in plaque erosion, however, remain little explored. We investigated the relationship of high-risk ESS metrics to culprit lesion proinflammatory/proatherogenic cells and cytokines/chemokines implicated in coronary plaque erosion in patients with acute coronary syndromes. In eroded plaques, low ESS, high ESS gradient, and steepness of plaque topographical slope associated with increased numbers of local T cells and subsets (CD4 ⁺ , CD8 ⁺ , natural killer T cells) as well as inflammatory mediators (interleukin [IL]-6, macrophage inflammatory protein-1β, IL-1β, IL-2).
Competing Interests: Dr Libby has received funding support from the National Heart, Lung, and Blood Institute (1R01HL134892, 1R01HL163099-01, R01AG063839, R01HL151627, R01HL157073, R01HL166538), and the RRM Charitable Fund. Dr Libby is an unpaid consultant to, or involved in clinical trials for Amgen, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Novo Nordisk, Novartis, and Sanofi-Regeneron. Dr Libby is a member of the scientific advisory board for Amgen, Caristo Diagnostics, CSL Behring, Eulicid Bioimaging, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, Novartis, PlaqueTec, Polygon Therapeutics, TenSixteen Bio, Soley Thereapeutics, and XBiotech, Inc. Dr Libby's laboratory has received research funding in the last 2 years from Novartis, Novo Nordisk and Genentech. Dr Libby is on the Board of Directors of XBiotech, Inc. Dr Libby has a financial interest in Xbiotech, a company developing therapeutic human antibodies, in TenSixteen Bio, a company targeting somatic mosaicism and clonal hematopoiesis of indeterminate potential (CHIP) to discover and develop novel therapeutics to treat age-related diseases, and in Soley Therapeutics, a biotechnology company that is combining artificial intelligence with molecular and cellular response detection for discovering and developing new drugs, currently focusing on cancer therapeutics. Dr Libby's interests were reviewed and are managed by Brigham and Women's Hospital and Mass General Brigham in accordance with their conflict-of-interest policies. Dr Landmesser has received institutional research grants from Amgen, Abbott, Bayer and Novartis. Dr Abdelwahed receives consultancy fees from Boston Scientific and Shockwave. Dr Stone's laboratory was funded by the National Heart, Lung, and Blood Institute (R01HL146144-01A1 and R01HL140498). Dr Ahmed was supported by grants from the Swedish Heart-Lung Foundation (20200165 and 20230167), the Swedish Research Council (202100456), the Swedish Society of Medicine (SLS-961835), Erik and Edith Fernströms Foundation (FS-2021:0004), Karolinska Institutet (FS2020:0007), the Sweden-America Foundation, and the Swedish Heart Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(© 2024 The Authors.)