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In POTS, this signaling fails, leading to blood pooling in the lower extremities and a rapid, compensatory spike in heart rate

They promote the expression of catabolic enzymes (e.g., MMP-1, -2, -3, -13, and ADAMTS-4/5) and inhibit anabolic proteins like aggrecan and collagen II by activating signaling pathways such as NF-B, MAPK, and Toll-like receptors (TLR), ultimately leading to ECM degradation and tissue destruction (Yang et al., 2025