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This study demonstrates that cytoglobin (CYGB), an antioxidant enzyme expressed in smooth muscle cells (SMCs), negatively regulates the development of atherosclerotic fibrous caps. Using mice with SMC-specific CYGB deletion, researchers found that loss of CYGB increased fibrous cap thickness, collagen deposition, and SMC cellularity without affecting overall plaque size. CYGB expression in SMCs promotes their transdifferentiation toward a fibroblast-like phenotype, and the enzyme was confirmed to be present in human coronary atherosclerotic lesions.
Why it matters
Since fibrous cap rupture is the primary cause of heart attacks and strokes in atherosclerosis patients, understanding factors that control cap stability is crucial. This research identifies CYGB as a potential therapeutic target, where inhibiting this enzyme could theoretically strengthen fibrous caps and reduce the risk of life-threatening cardiovascular events.
Understand the Science
⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Rupture of the fibrous cap is the primary cause of clinical complications from atherosclerosis. Smooth muscle cells (SMCs) are a major contributor to fibrous cap development and stability through de-differentiation to extracellular matrix-producing cells. We previously showed that the antioxidant enzyme cytoglobin (CYGB) is expressed in vascular SMCs and regulates SMC dependent vascular remodeling and gene expression. In the present study, we investigated the function of SMC-CYGB in atherosclerosis. To this end, we generated a mouse line with SMC-specific deletion of Cygb and simultaneous SMC-lineage tracing. We found that SMC specific deletion of CYGB increased fibrous cap thickness in a 17-week PCSK9-AAV8 gain of function combined with Western diet mouse model of atherosclerosis. SMC specific deletion of CYGB increased collagen deposition and SMC cellularity of the fibrous cap in the absence of changes in total plaque and necrotic core sizes. CYGB expression in SMCs was associated with transdifferentiation towards a fibroblast-like, matrix remodeling phenotype. Finally, CYGB was expressed in the fibrous cap of human coronary atherosclerotic lesions and was associated with ACTA2 positive cells. These results provide first-time evidence that SMC-CYGB reduces plaque stability by decreasing cap thickness, collagen deposition, and SMC cellularity.
Source: Smooth Muscle Cell Cytoglobin is a Negative Regulator of Atherosclerotic Fibrous Cap Development