Extracellular vesicles originating from the mechanical microenvironment in the pathogenesis and applications for cardiovascular diseases

Figures

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  Fig. 1. Fundamental biological forces operate within the microenvironment. The extracellular matrix constitutes a complex network of proteins, proteoglycans, and glycoproteins. Hydrostatic pressure is prevalent in fluid-containing tissues and organs, such as blood vessels. Blood flow within the human vasculature generates characteristic fluid shear forces. Tensile forces play a crucial role in muscle and joint movement, atherogenesis, cardiovascular remodeling, and various cellular activities.

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  Fig. 2. The mechanical microenvironment plays a crucial role in regulating the mechanism of EVs release. In conjunction with cytoskeletal proteins, the extracellular matrix and integrins influence the fusion and release of MVBs and the plasma membrane by activating the transcription of YAP/TAZ and the PI3K/AKT pathway. Under mechanical stimulation, Ca2+ ions traverse activated mechanical channels, thereby regulating secretory vesicles within the endoplasmic reticulum. Additionally, shear force modulates cytoskeletal proteins by activating Rab proteins, subsequently impacting the fusion of MVBs with the plasma membrane.

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  Fig. 3. EVs and cardiovascular diseases in the mechanical microenvironment. Endothelial cells and cardiomyocytes produce EVs that contain significant amounts of RNA and proteins when subjected to shear and stretch forces. These EVs can be delivered to target cells, exerting cardioprotective effects through angiogenesis, cell migration, inflammatory response, and vascular remodeling. Additionally, they regulate blood pressure and influence the progression of atherosclerosis.