Figure 2.

Effects of mechanical stretch and endoplasmic reticulum (ER) stress responses. A: pathological stretch induces a phenotypic transition from contractile to synthetic (proliferative) phenotype in smooth muscle cells (SMCs). B: mutations that impair the actin cytoskeleton reduce force generation and inhibit development of passive tension and force transmission through the extracellular matrix (ECM). Mechanical signals are transmitted from the cell surface, through the cytoskeleton and contractile apparatus via the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex to the genome, thereby affecting gene expression. If this force transmission is impaired by mutations affecting cytoskeletal filaments, physiological SMC gene expression in response to extracellular forces may be disrupted. C: endoplasmic reticulum (ER) is greatly expanded in the SMC synthetic phenotype to increase production of extracellular matrix (ECM) proteins and matrix metalloproteases (MMPs). If the cell cannot meet the increased protein production demand, an unfolded protein response (UPR) may be triggered as part of the ER stress response. This figure uses icons derived from the Reactome Icon Library by CSHL, OICR and EBI. F-actin, filamentous actin.