Blockade of the TLR4-MD2 complex lowers blood pressure and improves vascular function in a murine model of type 1 diabetes.

Scientific Reports
Amanda Almeida de OliveiraKenia Pedrosa Nunes

Abstract

While the pathogenesis of diabetes-induced high blood pressure (BP) is not entirely clear, current evidence suggests that Toll-like receptor 4 (TLR4) is a key player in the mechanisms associated with hypertension. However, it is unknown whether this receptor affects BP under type 1 diabetes. Likewise, there is insufficient knowledge about the role of TLR4 in diabetes-associated vascular dysfunction of large arteries. To narrow these gaps, in this study, we investigated if blockade of the TLR4-MD2 complex impacts BP and vascular function in diabetic rats. We injected streptozotocin in male Sprague Dawley rats and treated them with a neutralizing anti-TLR4 antibody for 14 days. BP was directly measured in conscious animals at the end of the treatment. In another set of experiments, we excised the aorta from control and diabetic animals, and measured TLR4 and MD2-a co-receptor that confers functionality to TLR4-levels by Western blotting. We also performed functional studies and evaluated ROS levels with and without a pharmacological inhibitor for TLR4 as well as for MD2. Additionally, we scrutinized a large human RNA-Seq dataset of aortic tissue to assess the co-expression of TLR4, MD2, and subunits of the vascular NADPH oxidases...Continue Reading

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Citations

Apr 2, 2021·Circulation Research·Stephanie M CicaleseRita C Tostes
May 30, 2021·Vascular Pharmacology·Amanda Almeida de Oliveira, Kenia Pedrosa Nunes

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Methods Mentioned

BETA
RNA-Seq
protein assay
glycosylation

Software Mentioned

ImageJ
Pandas

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