Smooth Muscle Cell Plasticity as a Central Determinant of Plaque Stability

Figures

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  The TGF-β paradox in an inflamed atherosclerotic artery. Smooth muscle “conductor” inside an atherosclerotic artery, confronted with a chaotic TGF-β signal that can drive either repair (capped plaque) or destruction (ulcerated core), illustrating context-dependent TGF-β effects on SMC behavior. Conceptual schematic created in Adobe Photoshop and Illustrator with AI-assisted tools; no experimental or patient data were used or altered

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  Fig. 1. Smooth muscle cell phenotypic spectrum in plaques. Representative marker genes for each SMC-derived state are indicated on the figure: contractile (ACTA2, MYH11, CNN1, TAGLN), synthetic/cap-building (COL1A1, COL3A1, FN1), MSC-like progenitor (PDGFRA, CD248, THY1), foam-like (PLIN2, APOE, PPARG), osteochondral-like (SOX9, RUNX2, SPP1), and macrophage-like (LGALS3, CD68, LST1). Conceptual schematic created in Adobe Photoshop and Illustrator with AI-assisted tools; no experimental or patient data were used or altered

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  Fig. 2. Developmental origin shapes regional plaque burden and smooth muscle behavior in coronary, ascending, and abdominal vessels. A. Transparent heart schematic showing the coronary bed and aortic root (teal), which derive from epicardial lineages and form a small-caliber arterial bed with disproportionately high plaque burden and event risk. Patchy yellow plaques along the teal coronaries illustrate the focal nature of coronary atherosclerosis. B. Aortic map summarizing developmental origin and typical plaque distribution along the proximal aorta. The coronary/root region (teal, ①) is epicardial-derived and experiences high plaque burden. The ascending arch (purple, ②) contains a mixed population of second heart field (SHF) and cardiac neural crest SMCs; plaques preferentially accumulate at the inner curvature, whereas the outer curvature remains relatively spared. The thoracic and abdominal aorta (red, ③) are populated largely by mesodermal (somitic) SMCs and tend to develop bulky plaques and medial degeneration. Yellow patches indicate lipid-rich atherosclerotic lesions in each segment. C. Cross-sectional views illustrate distinct plaque architectures and SMC cap phenotypes in…

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  Fig. 3. TGF-β “decision console” on a smooth muscle cell. Cartoon cross-section of the pericellular space around a medial smooth muscle cell. The band at the bottom represents the SMC plasma membrane, with short matrix projections extending into a structured extracellular matrix network. Latent and active TGF-β complexes are shown clustered close to the surface, where they can be activated and sensed. The DJ-style console on the membrane illustrates the four variables discussed in this section: ligand dose, duration of signaling, the cellular audience (neighboring SMCs, endothelial cells, macrophages, fibroblasts), and the state of the surrounding matrix (organized versus disturbed). In an intact medial wall, these controls sit in a homeostatic range and TGF-β/Smad signaling helps keep SMCs contractile and the vessel stable. When dose, timing, matrix mechanics, or the mix of neighboring cells shifts into a disease range, the same pathway can drive SMC phenotypic switching, maladaptive matrix remodeling, and progression of atherosclerotic lesions. Conceptual schematic created in Adobe Photoshop and Illustrator with AI-assisted tools; no experimental or patient data were used or altered