ArticleHypertension (Dallas, Tex. : 1979)2016
Vascular ADAM17 as a Novel Therapeutic Target in Mediating Cardiovascular Hypertrophy and Perivascular Fibrosis Induced by Angiotensin II.
Article in Hypertension (Dallas, Tex. : 1979), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 79 citations in OpenAlex.
- Renin-Angiotensin Signaling and Vascular Function: Insights into Health and Disease.Acta physiologica (Oxford, England) · 2026Review
- The Role of Furin in Hallmarks of Aneurysms: A Focus On Its Substrates.Current atherosclerosis reports · 2026Review
- Inositol Requiring Enzyme 1α Mediates Hypertension and Vascular Remodeling.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Dual roles of ADAM17: from fibroblast foe to myofibroblast friend.Cardiovascular research · 2026Article
- STATs Signaling Pathways in Acute Pancreatitis: Mechanisms and Regulation.International journal of medical sciences · 2026Review
- The role of OTUD1-mediated deubiquitination in disease pathogenesis: from molecular mechanisms to clinical translation.Frontiers in immunology · 2026Review
- ADAM17 as a promising therapeutic target: from structural basis to inhibitor discovery in human diseases.Frontiers in pharmacology · 2025Review
- Targeting GPR39 in structure-based drug discovery reduces Ang II-induced hypertension.Communications biology · 2024Article
- Cardiac and perivascular myofibroblasts, matrifibrocytes, and immune fibrocytes in hypertension; commonalities and differences with other cardiovascular diseases.Cardiovascular research · 2024Review
- Mitochondrial fission inhibition protects against hypertension induced by angiotensin II.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Article
- Milestone Papers on Signal Transduction Mechanisms of Hypertension and Its Complications.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Combination of ADAM17 knockdown with eplerenone is more effective than single therapy in ameliorating diabetic cardiomyopathy.Frontiers in pharmacology · 2024Article
- CircHIPK2 facilitates phenotypic switching of vascular smooth muscle cells in hypertension.Journal of human hypertension · 2023Article
- IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating EGR1 in male mice.Nature communications · 2023Article
- Infused juice concentrate of Japanese plum Prunus mume attenuates inflammatory vascular remodeling in a mouse model of hypertension induced by angiotensin II.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Article
- Angiotensin II Type 1A Receptor Expressed in Smooth Muscle Cells is Required for Hypertensive Vascular Remodeling in Mice Infused With Angiotensin II.Hypertension (Dallas, Tex. : 1979) · 2023Article
- The matricellular protein CCN3 supports lung endothelial homeostasis and function.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Central role for BRAF in cardiac hypertrophy: rethinking the pathological-physiological divide.Clinical science (London, England : 1979) · 2023Article
- Cardiomyocyte cohesion is increased after ADAM17 inhibition.Frontiers in cell and developmental biology · 2023Article
- miR-145 Alleviates Smooth Muscle Cell Phenotype Transition via ADAM17-Mediated ACE2 Shedding.International journal of hypertension · 2023Article
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12 authors at 1 institution in 1 country.
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Abstract
Angiotensin II (AngII) has been strongly implicated in hypertension and its complications. Evidence suggests the mechanisms by which AngII elevates blood pressure and enhances cardiovascular remodeling and damage may be distinct. However, the signal transduction cascade by which AngII specifically initiates cardiovascular remodeling, such as hypertrophy and fibrosis, remains insufficiently understood. In vascular smooth muscle cells, a metalloproteinase ADAM17 mediates epidermal growth factor receptor transactivation, which may be responsible for cardiovascular remodeling but not hypertension induced by AngII. Thus, the objective of this study was to test the hypothesis that activation of vascular ADAM17 is indispensable for vascular remodeling but not for hypertension induced by AngII. Vascular ADAM17-deficient mice and control mice were infused with AngII for 2 weeks. Control mice infused with AngII showed cardiac hypertrophy, vascular medial hypertrophy, and perivascular fibrosis. These phenotypes were prevented in vascular ADAM17-deficient mice independent of blood pressure alteration. AngII infusion enhanced ADAM17 expression, epidermal growth factor receptor activation, and endoplasmic reticulum stress in the vasculature, which were diminished in ADAM17-deficient mice. Treatment with a human cross-reactive ADAM17 inhibitory antibody also prevented cardiovascular remodeling and endoplasmic reticulum stress but not hypertension in C57Bl/6 mice infused with AngII. In vitro data further supported these findings. In conclusion, vascular ADAM17 mediates AngII-induced cardiovascular remodeling via epidermal growth factor receptor activation independent of blood pressure regulation. ADAM17 seems to be a unique therapeutic target for the prevention of hypertensive complications.
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