Mechanical shear stress influences endothelial RNA methylation in atherosclerosis and pulmonary arterial hypertensionMechanical forces on blood vessel cells may change how they repair themselves

Hemodynamic shear stress is a fundamental biomechanical cue that shapes endothelial phenotypes and contributes to vascular diseases. Although flow-responsive transcription factors such as KLF2 and KLF4 are well recognized, how mechanical forces converge on epitranscriptomic mechanisms to regulate RNA fate remains incompletely understood. Emerging evidence identifies N6-methyladenosine (m6A) modification as a dynamic regulator of non-coding RNA stability and endothelial function, yet its integration into shear-dependent remodeling has not been systematically explored. This review synthesizes current evidence on the interplay between shear stress and the m6A regulatory machinery and discusses how epitranscriptomic modulation of coding and non-coding RNAs may contribute to endothelial plasticity. Within this broader framework, the KLF2/4–METTL3–H19 pathway is presented as a representative mechanistic module illustrating how flow-responsive transcriptional programs may intersect with RNA methylation processes and reader-mediated transcript regulation. The potential implications of such interactions for endothelial-to-mesenchymal transition, barrier integrity, angiogenesis, and vascular diseases—including atherosclerosis, pulmonary arterial hypertension, and diabetic microangiopathy—are discussed. This integrated perspective highlights the emerging role of mechano-epitranscriptomic crosstalk in vascular biology and identifies directions for future investigation.