The most prevalent vascular disease, atherosclerosis (AS), has a significant role in cerebral infarction, stroke, and cerebral ischemia-reperfusion damage. It develops from the intima and is characterized by a disturbance of lipid metabolism [1], [2], [3]. A joint high-probability event in AS pathophysiology is the abnormal growth and migration of vascular smooth muscle cells (VSMCs) from the media to the subendothelium, followed by the production of collagen fibers and the deposition of lipids [4], [5].

A category of non-coding RNAs known as circular RNAs (circRNAs) is distinguished by covalently closed loops produced by back-splicing [6], [7]. CircRNAs include covalent loops produced from introns, exons or intergenic regions, unlike linear RNA and single-stranded transcripts, allowing them to resist RNases, preserve their tissue specificity and abundance, and have a vital function in AS process [8], [9], [10], [11], [12].

Numerous investigations have shown that circRNAs containing internal ribosome entry sites (IRES) or extensive methylation sites can encode proteins and potentially impact physiological behaviors [13], [14]. In AS, circRNAs act as sponges for proteins and microRNAs (miRNAs). New investigations have verified that some circRNAs can be translated into proteins, while most cannot. Circ-FBXW7 can be translated into protein FBXW7-185aa, which coordinately regulates the expression of c-Myc and inhibits cell proliferation by limiting cell cycle progression [15]. However, it remains unknown whether circRNAs can regulate the initiation and progression of AS through encoding proteins.

The cyclic adenosine monophosphate (cAMP) pathway can inhibit vascular intimal hyperplasia by regulating downstream effector molecules to inhibit vascular remodeling [16]. Its main target is cAMP-dependent protein kinase A (PKA) [17]. Intimal thickening resulting from VSMCs migration and proliferation is the most critical cellular basis for vascular remodeling [18]. Phosphodiesterase (PDE) functions to hydrolyze cAMP and cGMP, thereby terminating the biochemical actions conducted by these second messengers. Mutations in the PDE3 gene of VSMCs in hypertension and brachydactyly syndrome (HTNB) patients led to enhanced PDE3 phosphorylation, decreased intracellular cAMP levels, and enhanced proliferation of VSMCs [19]. In addition, increasing cAMP can inhibit VSMCs migration and intimal hyperplasia, thereby protecting the vascular wall [20].

We identified circLARP1B, downregulated in atherosclerotic plaque tissue, by analyzing sequencing data in this study. Furthermore, our in vitro functional studies revealed that overexpression of circLARP1B promotes the proliferation and migration of VCMCs. Subsequent studies showed that circLARP1B encodes the protein circLARP1B-243aa. Mechanistically, circLARP1B-243aa promotes VSMCs migration and growth by upregulating PDE4C to inhibit the cAMP signaling pathway. Our results suggest that circLARP1B can enhance VSMCs migration and proliferation through the encoded protein circLARP1B-243aa, making it an AS biomarker and potential treatment target.