The primary cilium-autophagy axis in vascular homeostasis and cardiovascular disease: mechanistic crosstalk and evidence boundaries

Abstract

Primary cilia are microtubule-based sensory organelles located on the cell surface and function as cellular signaling antennae for mechanical and chemical cues. In the vascular endothelium, they participate in shear-stress sensing, Ca2+ signal transduction, eNOS activity regulation and vascular homeostasis. Autophagy is a conserved lysosome-dependent degradative pathway that maintains cardiovascular cell homeostasis by removing damaged organelles, regulating lipid metabolism, restraining inflammatory activation and preserving proteostasis. In this review, we discuss the bidirectional regulatory relationship between primary cilia and autophagy. Primary cilia may influence autophagic activity through Ca2+/AMPK/mTOR, Hedgehog and PI3KC2α-related pathways, whereas autophagy can reciprocally regulate ciliary homeostasis through cilia-related proteins such as OFD1 and IFT20. This cilium-autophagy interface may contribute to hypertension, atherosclerosis and aortic aneurysm by modulating endothelial mechanosensing, mitochondrial quality control, lipid handling, ROS homeostasis and inflammatory responses. Because direct evidence for causal cilium-autophagy crosstalk in the cardiovascular system remains limited, we distinguish established mechanisms from biologically plausible extrapolations and disease-associated observations. By integrating evidence from ciliary mechanosensing, autophagy regulation and vascular pathological remodeling, this review proposes the primary cilium-autophagy axis as a conceptual framework linking hemodynamic disturbance, organelle stress and vascular disease progression, and provides a basis for refining mechanistic hypotheses and potential therapeutic targets.