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Figure 2. The Role of Estrogen in Cardiac and Brain Cellular Mechanisms: Impacts on Health and Disease. This illustration highlights the effects of E2 on cardiac and brain cells via ER-mediated pathways. In cardiac cells, estrogen enhances vasodilation through NO signaling, reduces fibrosis by upregulating VEGF and Lyve-1, and lowers LDL levels via ApoB-100 regulation. Conversely, it inhibits detrimental effects, such as superoxide and TNF-α production, while modulating Ca²⁺ accumulation in mitochondria. In brain cells, E2 promotes neuroprotection by increasing hippocampal neurogenesis (via BDNF) and synaptic plasticity (PSD95) while supporting vasodilation (PGI2). It mitigates neuroinflammatory responses by inactivating microglia (Cx3CR1), suppressing proinflammatory cytokines (TNF-α, IL-1β, IL-6), and enhancing Aβ degradation through NEP regulation. Additionally, estrogen inhibits apoptotic pathways by decreasing cytochrome c release and caspase activation. These pathways demonstrate estrogen's role in reducing oxidative stress, balancing mitochondrial function, and influencing gene expression to protect against cardiovascular and neurodegenerative diseases. E2: Estrogen; ER: estrogen receptor; NO: nitric oxide; VEGF: vascular endothelial growth factor; Lyve-1: Lymphatic vessel endothelial hyaluronan receptor 1; LDL: low-density lipoprotein; ApoB: Apolipoprotein B; TNF-α: tumor necrosis factor alpha; BDNF: brain-derived neurotrophic factor; PSD95: postsynaptic density 95; PGI2: prostaglandin I2; Cx3CR1: CX3C chemokine receptor 1; IL-1β: interleukin-1beta; IL-6: interleukin-6; Aβ: amyloid beta; NEP: neprilysin. Created in BioRender. Zouein, F. (2025), Available from: https://BioRender.com/oicbvbg.