Abstract Body: Background: Recent studies have shown that the autonomic nervous system plays a crucial role in regulating the initiation and progression of atherosclerosis in peripheral arteries. Animal studies suggest that intracranial arteries are innervated by unmyelinated autonomic nerves. However, the role of the autonomic nervous system in human intracranial atherosclerosis remains poorly understood.
Methods: We utilized intracranial arterial tissue from human autopsies and employed single-cell RNA sequencing, transmission electron microscopy, and multiple immunofluorescence staining to investigate the mechanisms underlying the initiation and progression of atherosclerosis.
Results: We identified a population of Schwann cells in the walls of intracranial arteries. This discovery challenges conventional understanding, as Schwann cells are traditionally associated with the peripheral nervous system, and their presence in intracranial arteries has not been previously reported. Using transmission electron microscopy, we further found lamellar myelin structures within the arterial media, and the number of myelin sheaths was higher in the plague group than in the control group, suggesting that Schwann cells may participate in myelination within the arterial wall and then influence plaque progression. To elucidate the cellular communication networks involving Schwann cells, we utilized the CellChat analytical framework and found that Schwann cells had robust crosstalk with vascular smooth muscle cells (VSMCs). These interactions were mediated by a complex network of signaling molecules, including those implicated in axon growth, axon guidance, and cell adhesion, suggesting that Schwann cells may actively modulate VSMCs behavior and influence the pathological remodeling of the arterial wall characteristic of atherosclerotic lesions. Multiple immunofluorescence staining revealed that the plaque group exhibited a greater density of nerve fiber innervation compared to the control group.
Conclusions: Our study provides evidence that human intracranial arteries are innervated by myelinated fibers. Schwann cells may participate in the initiation and progression of intracranial atherosclerosis by facilitating axon growth and rearrangement. These results not only enhance our understanding of cellular diversity within atherosclerotic lesions but also highlight Schwann cells as a potential therapeutic target.