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| Content Provider | Springer Nature Link |
|---|---|
| Author | Schmidt, Luke Carrillo Sepulveda, Maria Alicia |
| Copyright Year | 2015 |
| Abstract | Increased vascular smooth muscle cell (VSMC) contraction is an early and critical contributor to the pathogenesis of vascular dysfunction in diabetes; however, knowledge regarding the underlying mechanisms is scarce. Toll-like receptor 2 (TLR2), a well-known component of the innate immunity, is expressed in VSMC and recently has been identified to be systemically activated in diabetes. Whether TLR2 is locally activated in the diabetic blood vessels and have effect on contraction is not known. In the current study, we examined the role of TLR2 in increased vascular contraction in diabetes. Utilizing rat model of type 1 diabetes (induced by streptozotocin (STZ)), we demonstrated that aortas from STZ-diabetic rats exhibit increased expression of TLR2 and its adaptor protein, myeloid differentiation primary response 88 (MyD88), as well as enhanced protein–protein interaction between TLR2 and MyD88, suggesting a TLR2 signaling activation. Blockade of TLR2 in intact aortas using anti-TLR2 antibody attenuated increased vascular contraction in STZ-diabetic rat as assessed by wire myograph. Activation of TLR2 by specific ligand in primary aortic VSMC cultures triggered activation of RhoA which was exacerbated in cells from STZ-diabetic rats than control rats. Activation of RhoA was accompanied by phosphorylation and therefore activation of its downstream targets myosin phosphatase target subunit I and myosin light chain (markers of VSMC contraction). Taken together, these results provide evidence for the role of TLR2 in increased contraction in diabetic blood vessels that involves RhoA signaling. Thus, targeting vascular TLR2 offers a promising drug target to treat vascular dysfunction in diabetes. |
| Starting Page | 2361 |
| Ending Page | 2374 |
| Page Count | 14 |
| File Format | |
| ISSN | 00316768 |
| Journal | Pflügers Archiv |
| Volume Number | 467 |
| Issue Number | 11 |
| e-ISSN | 14322013 |
| Language | English |
| Publisher | Springer Berlin Heidelberg |
| Publisher Date | 2015-01-21 |
| Publisher Place | Berlin, Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | RhoA TLR2 Type 1 diabetes Vascular contraction VSMC Human Physiology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Physiology (medical) Clinical Biochemistry |
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