B Cell TGF-beta1 deficiency prevents VSMC-macrophage phenotype shift and ameliorates advanced atherosclerosis

Background/Introduction Atherosclerosis, a chronic inflammatory disease of the arterial wall, is a leading cause of cardiovascular diseases. B cells contribute to both systemic and local immune responses within atherosclerotic plaques via cellular immune responses modulation, antigen presentation, and cytokine production, thereby shaping the inflammatory microenvironment of the plaque. Purpose The study aimed to determine the impact of B cell-specific TGF-β1 deficiency on plaque development, immune cell infiltration, and systemic responses, providing insights into the role of B cells derived TGF-β1 during atherogenesis. Methods Apoe-/- mice and Apoe-/- mice transgenic mice with B cell-specific TGF-β1 deficiency were fed a high-cholesterol diet for 11 weeks to induce advanced atherosclerosis. Upon sacrifice, serum analysis was performed, and atherosclerotic plaques size and cellular composition were assessed. Results Transgenic mice with B cell-specific TGF-β1 deficiency exhibited reduced atherosclerotic plaques lipid accumulation and lower levels of total cholesterol and LDL-C. Flow cytometry analysis of the aortic arch cells revealed decreased macrophages and VSMC-derived foam cells, alongside preserved VSMC phenotype, increased collagen deposition, and reduced necrotic core formation. Additionally, these mice showed a significant increase in the atheroprotective antibodies - IgM, IgG2b, and IgG1 targeting oxLDL, suggesting enhanced protective immune responses. Conclusion These findings highlight the surprising atheroprotective effect of the deficiency of B cell-derived TGF-β1 in reshaping the atherosclerotic plaque composition and lowering the cholesterol levels and driving atheroprotective antibodies in advanced atherosclerosis.