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This narrative review of the scientific literature highlights discoveries about the PIEZOs, PIEZO1 and PIEZO2, in vascular biology from the embryo to adult stages including in vascular and valve formations, vascular expansion and arrest, lymphatic and venous integrity, blood pressure regulation, the aortic baroreceptor reflex, microvascular density for muscle and physical exercise capabilities and the regulation of lipid homeostasis, cerebral hyperemia and leukocyte extravasation. Concepts are discussed for how the channels work at the molecular level and integrate with other cell components and how they signal downstream for appropriate tissue responses. A PIEZO\u2010centric hypothesis is debated for the core fluid flow sensing property of cardiovascular biology. PIEZO contributions to vascular and vascular related disease problems are discussed. 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