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However, chronic elevation in afterload profoundly impairs myocardial energetics, increasing myocardial oxygen demand and wall stress which drives myocardial hypertrophy, fibrosis, and adverse ventricular remodeling through activation of intracellular signaling cascades, including transforming growth factor-beta (TGF-β), mitogen-activated protein kinase (MAPK), and nuclear factor kappa-B (NF-κB) pathways [70,71]
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