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. 2021 Aug 26;10(9):2209. doi: 10.3390/cells10092209

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Examples of mechanical stretch-induced pathways in SMCs. (A) Pathways activated by physiological cyclic stretching (< 10% elongation) keep the SMCs into a differentiated state, characterized by a reduced proliferation, migration, and inflammation and accompanied by high levels of contractile marker genes. (B) On the other hand, the exposure of SMC to supraphysiological cyclic stretching (> 15% elongation) induces phenotypic modulation from a contractile to a synthetic state. The pathways activated by this high intensity stretching profile induce an increase in cell proliferation, migration, and inflammation and a decrease in the expression of contractile markers. (TGF-β1) Transforming growth factor-beta 1, (TGFBR1) Transforming growth factor-beta receptor 1, (Smad2/5) SMAD family members 2 and 5, (SIRT6) Sirtuin 6, (SIRT1) Sirtuin 1, (FOXO3) Forkhead transcription factor 3a, (HDAC) Histone deacetylase, (AT1R) Angiotensin II receptor type I, (ACE) angiotensin-converting enzyme, (pERK) phosphorylated extracellular-regulated protein kinase, (miR-145) microRNA 145, (PI3K) phosphoinositide 3-kinase, (YAP) Yes-associated protein 1, (TAZ) transcriptional coactivator with a PDZ-binding motif, (Ras/Rac) family of small GTPases, (P38) P38 mitogen-activated protein kinases, (NF-κB) nuclear factor kappa-light-chain-enhancer of activated B cells, (?) unknown receptor/regulator, and extracellular matrix (ECM).