Activation of BMP4-pSmad1/5 pathway impairs the function of VSMCs in intracranial aneurysms

Intracranial aneurysms (IAs) are characterized by abnormal dilatation of the cerebral vessels. Vascular smooth muscle cells (VSMCs) are implicated in maintaining vascular homeostasis. Disordered VSMCs are one of the most common causes for occurrence and development of IAs. The bone morphogenetic protein 4 (BMP4) signalling pathway is involved in regulating cell proliferation, apoptosis, and differentiation. This study aimed to investigate the effects of BMP4 on VSMCs and its underlying mechanisms. BMP4 was upregulated in the VSMCs of IAs and caused apoptosis of VSMCs through Smad1/5 phosphorylation. In addition, BMP4 overexpression significantly promoted the proliferation and migration of VSMCs and induced a phenotypic transformation from contractile to inflammatory. Our findings facilitate further understanding of the occurrence and development of IAs and provide a potential therapeutic target.