Fig. 7

Schematic illustrating the cascade of intracellular events culminating in Aβ-induced Ca²⁺ influx, ROS production, and VSMC contractility. Aβ (in either monomeric, oligomeric, or fibrillar form) may interact with cell surface or extracellular matrix HSPG, leading to intracellular Ca²⁺ influx (early event, ~2 mins) and ROS production (later event, ~30 mins). Toxic ROS species may directly damage the VSMC contractile machinery leading to a hypercontractile phenotype. Also, via an independent or interdependent pathway, intracellular Ca²⁺ may bind to calmodulin to activate myosin light chain kinase (MLCK) and facilitate VSMC contraction. Interference with Aβ-HSPG binding via treatment with heparin or heparinase can mitigate these toxic effects of Aβ