ArticleHypertension research : official journal of the Japanese Society of Hypertension2015
TLR4 is a critical regulator of angiotensin II-induced vascular remodeling: the roles of extracellular SOD and NADPH oxidase.
Article in Hypertension research : official journal of the Japanese Society of Hypertension, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 57 citations in OpenAlex.
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- The Impacts of Animal-Based Diets in Cardiovascular Disease Development: A Cellular and Physiological Overview.Journal of cardiovascular development and disease · 2023Review
- Female mice are protected from impaired parenchymal arteriolar TRPV4 function and impaired cognition in hypertension.American journal of physiology. Heart and circulatory physiology · 2023Article
- Umbilical Cord Mesenchymal Stem Cells Overexpressing Heme Oxygenase-1 Promotes Symptoms Recovery in Cystitis Rats by Alleviating Neuroinflammation.Stem cells international · 2023Article
- Angiotensin-II activates vascular inflammasome and induces vascular damage.Vascular pharmacology · 2021Article
- Early life stress induces dysregulation of the heme pathway in adult mice.Physiological reports · 2021Article
- Toll-Like Receptors in the Pathogenesis of Essential Hypertension. A Forthcoming Immune-Driven Theory in Full Effect.International journal of molecular sciences · 2021Review
- TREM-1 orchestrates angiotensin II-induced monocyte trafficking and promotes experimental abdominal aortic aneurysm.The Journal of clinical investigation · 2021Article
- Cognitive impact of COVID-19: looking beyond the short term.Alzheimer's research & therapy · 2020Review
- The role of Immunity in Fabry Disease and Hypertension: A Review of a Novel Common Pathway.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2020Review
- Blockade of the TLR4-MD2 complex lowers blood pressure and improves vascular function in a murine model of type 1 diabetes.Scientific reports · 2020Article
- Long-Chain Non-Coding RNA Metastasis-Related Lung Adenocarcinoma Transcript 1 (MALAT1) Promotes the Proliferation and Migration of Human Pulmonary Artery Smooth Muscle Cells (hPASMCs) by Regulating the MicroRNA-503 (miR-503)/Toll-Like Receptor 4 (TLR4) Signal Axis.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Vasculoprotective effects ofJournal of traditional and complementary medicine · 2020Article
- The Role of Toll-like Receptors in Atherothrombotic Cardiovascular Disease.ACS pharmacology & translational science · 2020Review
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8 authors at 3 institutions in 2 countries.
Funding
Abstract
Toll-like receptor 4 (TLR4) and angiotensin II (AngII) induce vascular remodeling through the production of reactive oxygen species (ROS). AngII has also been shown to increase antioxidant enzyme extracellular superoxide dismutase (ecSOD). However, the roles of TLR4 in Ang II-induced ROS production, vascular remodeling and hypertension remain unknown. Mice lacking TLR4 function showed significant inhibition of vascular remodeling in response to chronic AngII infusion, with no impact on blood pressure. The increases in ROS level and NADPH oxidase activity in response to AngII infusion were markedly blunted in TLR4-deficient mice. Similar effects were observed in wild-type (WT) mice treated with a sub-depressor dose of the AT1 receptor antagonist irbesartan, which had no effects on TLR4-deficient mice. Intriguingly, the AngII infusion-induced increases in ecSOD activity and expression were rather enhanced in TLR4-deficient mice compared with WT mice, whereas the expression of the proinflammatory chemokine MCP-1 was decreased. Importantly, AngII-induced vascular remodeling was positively correlated with NADPH oxidase activity, ROS levels and MCP-1 expression levels. Notably, chronic norepinephrine infusion, which elevates blood pressure without increasing ROS production, did not induce significant vascular remodeling in WT mice. Taken together, these findings suggest that ROS elevation is required for accelerating vascular remodeling but not for hypertensive effects in this model. We demonstrated that TLR4 plays a pivotal role in regulating AngII-induced vascular ROS levels by inhibiting the expression and activity of the antioxidant enzyme ecSOD, as well as by activating NADPH oxidase, which enhances inflammation to facilitate the progression of vascular remodeling.
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