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Spatial Transcriptomic Approach to Understanding Coronary Atherosclerotic Plaque Stability.
Gastanadui, Maria G; Margaroli, Camilla; Litovsky, Silvio; Richter, Robert P; Wang, Dezhi; Xing, Dongqi; Wells, J Michael; Gaggar, Amit; Nanda, Vivek; Patel, Rakesh P; Payne, Gregory A.
Afiliación
  • Gastanadui MG; Department of Medicine, Division of Cardiovascular Disease (M.G.G., G.A.P.), University of Alabama at Birmingham.
  • Margaroli C; Cardiopulmonary Research Program, Department of Medicine (M.G.G., D.X., J.M.W., A.G., R.P.P., G.A.P.), University of Alabama at Birmingham.
  • Litovsky S; Department of Pathology, Division of Molecular and Cellular Pathology (C.M., V.N., R.P.P.), University of Alabama at Birmingham.
  • Richter RP; Program in Protease/Matrix Biology (C.M., R.P.R., D.X., J.M.W., A.G., R.P.P., G.A.P.), University of Alabama at Birmingham.
  • Wang D; Department of Pathology, Division of Anatomic Pathology (S.L.), University of Alabama at Birmingham.
  • Xing D; Comprehensive Cardiovascular Center (S.L., G.A.P.), University of Alabama at Birmingham.
  • Wells JM; Program in Protease/Matrix Biology (C.M., R.P.R., D.X., J.M.W., A.G., R.P.P., G.A.P.), University of Alabama at Birmingham.
  • Gaggar A; Department of Pediatrics, Division of Pediatric Critical Care (R.P.R.), University of Alabama at Birmingham.
  • Nanda V; Department of Pathology, Pathology Core Research Laboratory (D.W.), University of Alabama at Birmingham.
  • Patel RP; Cardiopulmonary Research Program, Department of Medicine (M.G.G., D.X., J.M.W., A.G., R.P.P., G.A.P.), University of Alabama at Birmingham.
  • Payne GA; Program in Protease/Matrix Biology (C.M., R.P.R., D.X., J.M.W., A.G., R.P.P., G.A.P.), University of Alabama at Birmingham.
Arterioscler Thromb Vasc Biol ; 44(11): e264-e276, 2024 Nov.
Article en En | MEDLINE | ID: mdl-39234691
ABSTRACT

BACKGROUND:

Coronary atherosclerotic plaques susceptible to acute coronary syndrome have traditionally been characterized by their surrounding cellular architecture. However, with the advent of intravascular imaging, novel mechanisms of coronary thrombosis have emerged, challenging our contemporary understanding of acute coronary syndrome. These intriguing findings underscore the necessity for a precise molecular definition of plaque stability. Considering this, our study aimed to investigate the vascular microenvironment in patients with stable and unstable plaques using spatial transcriptomics.

METHODS:

Autopsy-derived coronary arteries were preserved and categorized by plaque stability (n=5 patients per group). We utilized the GeoMx spatial profiling platform and Whole Transcriptome Atlas to link crucial histological morphology markers in coronary lesions with differential gene expression in specific regions of interest, thereby mapping the vascular transcriptome. This innovative approach allowed us to conduct cell morphological and spatially resolved transcriptional profiling of atherosclerotic plaques while preserving crucial intercellular signaling.

RESULTS:

We observed intriguing spatial and cell-specific transcriptional patterns in stable and unstable atherosclerotic plaques, showcasing regional variations within the intima and media. These regions exhibited differential expression of proinflammatory molecules (eg, IFN-γ [interferon-γ], MHC [major histocompatibility complex] class II, proinflammatory cytokines) and prothrombotic signaling pathways. By using lineage tracing through spatial deconvolution of intimal CD68+ (cluster of differentiation 68) cells, we characterized unique, intraplaque subpopulations originating from endothelial, smooth muscle, and myeloid lineages with distinct regional locations associated with plaque instability. In addition, unique transcriptional signatures were observed in vascular smooth muscle and CD68+ cells among plaques exhibiting coronary calcification.

CONCLUSIONS:

Our study illuminates distinct cell-specific and regional transcriptional alterations present in unstable plaques. Furthermore, we characterize spatially resolved, in situ evidence supporting cellular transdifferentiation and intraplaque plasticity as significant contributors to plaque instability in human coronary atherosclerosis. Our results provide a powerful resource for the identification of novel mediators of acute coronary syndrome, opening new avenues for preventative and therapeutic treatments.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria / Vasos Coronarios / Perfilación de la Expresión Génica / Placa Aterosclerótica / Transcriptoma Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria / Vasos Coronarios / Perfilación de la Expresión Génica / Placa Aterosclerótica / Transcriptoma Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos