Research Paper Volume 13, Issue 2 pp 2553—2574

TLR2 regulates angiotensin II-induced vascular remodeling and EndMT through NF-κB signaling

Ke Lin1,2, , Wu Luo1, , Jueqian Yan1, , Siyuan Shen1,2, , Qirui Shen1, , Jun Wang3, , Xinfu Guan4, , Gaojun Wu2, , Weijian Huang2, , Guang Liang1,2,4, ,

  • 1 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
  • 2 Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
  • 3 Department of Cardiology, Wenzhou Central Hospital and Affiliated Dingli Clinical Institute, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
  • 4 Affiliated Cangnan Hospital, Wenzhou Medical University, Cangnan 325800, Zhejiang, China

Received: August 18, 2020       Accepted: October 31, 2020       Published: December 9, 2020
How to Cite

Copyright: © 2020 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Excessive vascular remodeling has been shown in hypertensive patients. In experimental models of hypertensive vascular injury, such as angiotensin II (Ang II) challenged mice, toll like receptor 2 (TLR2) initiates inflammatory responses. More recently, studies have reported atypical endothelial to mesenchymal transition (EndMT) in vascular injuries and inflammatory conditions. Here, we aimed to investigate whether TLR2 mediates Ang II-induced vascular inflammation and initiates EndMT. In a mouse model of angiotensin II-induced hypertension, we show that aortas exhibit increased medial thickening, fibrosis, and features of EndMT. These alterations were not observed in TLR2 knockout mice in response to Ang II. TLR2 silencing in cultured endothelial cells confirmed the essential role of TLR2 in Ang II-induced inflammatory factor induction, and EndMT-associated phenotypic change. Mechanistically, we found Ang II activates nuclear factor-κB signaling, inducing pro-inflammatory cytokine production, and mediates EndMT in both cultured endothelial cells and in mice. These studies illustrate a novel role of TLR2 in regulating Ang II-induced deleterious vascular remodeling through the induction of EndMT. The studies also suggest that TLR2 may be targeted to alleviate hypertension-associated vascular injury.


Acta2: α-SMA, α-smooth muscle actin; Ang II: Angiotensin II; BAY: Bay 11-7805: nuclear factor-κB inhibitor; CD31: cluster of differentiation 31: endothelial marker; Col-3: collagen type 3; DAB: diaminobenzidine; DAPI: 4':6-diamidino-2-phenylindole; EGFP: enhanced green fluorescent protein; EndMT: endothelial to mesenchymal transition; GAPDH: glyceraldehyde-phosphate dehydrogenase; H&E: hematoxylin and eosin; HUVECs: Human umbilical vein endothelial cells; IL-1β: interleukin 1β; IL-6: interleukin 6; IκB-α: inhibitor of κBα; KO: knockout; NF-κB: nuclear factor kappa-B; PBS: phosphate-buffered saline; qPCR: quantitative polymerase chain reaction; SDS: sodium dodecyl sulfate; TLR2: Toll-like receptor 2; TGF-β1: transforming growth factor-β1; TNF-α: tumor necrosis factor-α; VE-Cadherin: vascular endothelial-cadherin; α-SMA: α smooth muscle actin.