摘要Postmenopausal estrogen deficiency predisposes women to atherosclerosis and cardiovascular pathologies.Edible dock protein-derived enzymatic hydrolysates(EDP),rich in ultra-short peptides,exhibit potential vascular protective properties,yet their efficacy in postmenopausal settings remains undefined.Utilizing an ovariectomized(OVX)rat model,we demonstrate that EDP,while not restoring estrogen/progesterone levels,significantly counteracted OVX-induced hyperlipidemia(reduced total cholesterol/low-density lipoprotein cholesterol,LDL-C)and rescued acetylcholine-mediated vasodilation in high-dose treatment(H-EDP).Single-cell transcriptomics of thoracoabdominal aortas revealed OVX-driven immune dysregulation:monocyte/macrophage expansion,T-cell depletion,disrupted Treg/Th17 equilibrium,and pro-inflammatory T cell receptor(TCR)/nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)activation.EDP rebalanced lymphoid populations(Treg/Th17 restoration),suppressed pro-inflammatory mediators,and enhanced anti-inflammatory transforming growth factor-β(TGF-β)signaling.In myeloid compartments,EDP attenuated neutrophilia and monocytosis while inhibiting atherogenic metabolism.Endothelial analysis highlighted EDP-enhanced lymphangiogenesis and immune-endothelial crosstalk via CXC chemokine ligand 12(CXCL12)/CXC chemokine receptor 4(CXCR4)axis.Smooth muscle cells exhibited EDP-mediated recovery of contractile SMC-Des populations,and modulation of leukocyte recruitment through vascular cell adhesion molecule-1(VCAM1)-Integrin α4β1 interactions.Fibroblast profiling showed EDP-induced expansion of Fibro-Barx1 subsets,restoring ECM homeostasis via Jag1-Notch2 pathways.Critically,EDP achieved these effects independent of estrogen restoration,establishing it as a hormone-independent therapeutic strategy to mitigate vascular dysfunction and immune-metabolic dysregulation in estrogen-deficient states.