Biomechanical stress-induced signaling in smooth muscle cells: an update.
The vascular wall is an integrated functional component of the circulatory system that is continually remodelling or is developing atherosclerosis in response to hemodynamic or biomechanical stress. In this process mechanical force is an important modulator of Vascular Smooth Muscle Cell (VSMC) morphology and function, including apoptosis, hypertrophy and proliferation that contribute to the development of atherosclerosis, hypertension, and restenosis. How VSMCs sense and transduce the extracellular mechanical signals into the cell nucleus resulting in quantitative and qualitative changes in gene expression is an interesting and important research field. It has been demonstrated that mechanical stress rapidly induces phosphorylation of the platelet-derived growth factor (PDGF) receptor, activation of integrin receptor, stretch-activated cation channels, and G proteins, which might serve as mechanosensors. Once the mechanical force is sensed, protein kinase C and Mitogen Activated Protein Kinases (MAPKs) were activated, leading to increased transcription factor activation. Thus, mechanical stresses can directly stretch the cell membrane and alter receptor or G protein conformation, thereby initiating signaling pathways, usually used by growth factors. Based on the progress in this field, this article attempts to formulate a biomechanical stress hypothesis, i.e. that physical force initiates signal pathways leading to vascular cell death and inflammatory response followed by VSMC proliferation. These findings have provided promising information for designing new drugs or genes for therapeutic interventions for vascular diseases.
Department of Cardiological Sciences, St. George's Hospital Medical School, London, UK.
Anthony
A
Shaw
Qingbo
Q
Xu
D000818:Animals; D017209:Apoptosis; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D016023:Integrins / Q000502:physiology; D007473:Ion Channels / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D020239:Receptor Cross-Talk; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical
D016023:Integrins; D007473:Ion Channels; D043562:Receptors, G-Protein-Coupled; D020794:Receptor Protein-Tyrosine Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins