Roles of primary cilia in cardiovascular diseases: mechanisms and therapeutic prospects

Cardiovascular diseases (CVDs) are one of the main causes of mortality and disability worldwide. Investigating their pathogenesis is crucial for the development of novel preventive strategies. Dysregulation of cilia, a type of sensory organelle, can lead to CVDs (hypertension, etc.). The loss of cilia can impair the ciliary perception ability of fluid shear stress, leading to reduced calcium influx and nitric oxide. It can contribute to hypertension and atherosclerosis. Cilia depletion can disrupt the PKC-Akt-NF-κB signaling pathway, which promotes aneurysm. It can downregulate connexin to drive aneurysm. Decreased palmitic acid can impair ciliary palmitoylation, thereby causing atherosclerosis. In addition, ciliary dysfunction is associated with the occurrence of heart diseases. The removal of cilia can induce congenital heart diseases by regulating the related signaling pathways (Wnt, etc.). The abundant accumulation of cilia at the myocardial injury site can mediate the TGF-β/Smad3 signaling pathway to induce cardiac fibrosis. It is reported that cilia are closely linked to valvulopathy and ventricular regeneration. Previous studies have shown that the maintenance of ciliary homeostasis can effectively ameliorate atherosclerosis and congenital heart defects. Stearoyl-CoA desaturase 1 inhibitors can maintain cilia homeostasis by upregulating ciliary palmitoylation, which alleviates atherosclerosis. A multifunctional opto-bio-hydrodynamic platform can regulate ciliary motion and treat congenital heart defects. However, the detailed mechanisms underlying ciliary abnormalities leading to CVDs remain unclear, hindering the development of cilia-targeted therapeutic approaches. We reviewed recent research progresses on the roles of cilia in CVDs and provided references and prospective strategies for the treatment of CVDs.