ArticleProceedings of the National Academy of Sciences of the United States of America2001
Conditional and targeted overexpression of vascular chymase causes hypertension in transgenic mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 93 citations in OpenAlex.
- Review
- Mast Cell and Basophil Granule Proteases -Frontiers in immunology · 2022Review
- The Angiotensin-(1-12)/Chymase axis as an alternate component of the tissue renin angiotensin system.Molecular and cellular endocrinology · 2021Review
- Extended Cleavage Specificity of the Rat Vascular Chymase, a Potential Blood Pressure Regulating Enzyme Expressed by Rat Vascular Smooth Muscle Cells.International journal of molecular sciences · 2020Article
- Extended cleavage specificities of two mast cell chymase-related proteases and one granzyme B-like protease from the platypus, a monotreme.International journal of molecular sciences · 2020Article
- Connexin37-Dependent Mechanisms Selectively Contribute to Modulate Angiotensin II -Mediated Hypertension.Journal of the American Heart Association · 2019Article
- Multifunctional Role of Chymase in Acute and Chronic Tissue Injury and Remodeling.Circulation research · 2018Review
- Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins.Cardiovascular research · 2016Article
- Mast cell proteases as pharmacological targets.European journal of pharmacology · 2016Review
- Enhanced vascular chymase-dependent conversion of endothelin in the diabetic kidney.Ochsner journal · 2013Article
- MFG-E8 activates proliferation of vascular smooth muscle cells via integrin signaling.Aging cell · 2012Article
- Long-term blood pressure control: is there a set-point in the brain?The journal of physiological sciences : JPS · 2012Review
- Mast cell proteases as protective and inflammatory mediators.Advances in experimental medicine and biology · 2011Review
- Mast cell peptidases: chameleons of innate immunity and host defense.American journal of respiratory cell and molecular biology · 2010Review
- Alpha 2-macroglobulin capture allows detection of mast cell chymase in serum and creates a reservoir of angiotensin II-generating activity.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- The intracellular renin-angiotensin system in the heart.Current hypertension reports · 2009Review
- Review
- Guinea pig chymase is leucine-specific: a novel example of functional plasticity in the chymase/granzyme family of serine peptidases.The Journal of biological chemistry · 2008Article
- Smooth muscle protein 22alpha-mediated patchy deletion of Bmpr1a impairs cardiac contractility but protects against pulmonary vascular remodeling.Circulation research · 2008Article
- Mast cell tryptases and chymases in inflammation and host defense.Immunological reviews · 2007Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We cloned a rat vascular chymase (RVCH) from smooth muscle cells (SMCs) that converts angiotensin I to II and is up-regulated in SMC from spontaneously hypertensive vs. normotensive rats. To determine whether increased activity of RVCH is sufficient to cause hypertension, transgenic mice were generated with targeted conditional expression of RVCH to SMC, with the use of the tetracycline-controlled transactivator (tTA). We confirmed conditional expression of RVCH by mRNA, protein, and chymase activity in the absence, but not in the presence, of dietary doxycycline. The systolic blood pressure (mmHg), measured by carotid artery cannulation at 10-12 weeks of age, was higher in tTA+/RVCH+ mice than in nonbinary transgenic littermates (136 +/- 4 vs. 109 +/- 3) (P < 0.05), as were the diastolic and mean pressures. Hypertension was completely reversed by doxycycline, suggesting a causal link with chymase expression. Medial thickening of mesenteric arteries from tTA+/RVCH+ mice vs. littermates (0.82 +/- 0.1 vs. 0.42 +/- 0.02) (P < 0.05) was associated with increased SMC proliferation, as judged by positive immunoreactivity, with the use of an antibody to the proliferating cell nuclear antigen. These structural changes were prevented by doxycycline. Perfusion myography of mesenteric arteries from tTA+/RVCH+ mice also revealed increased vasoconstriction in response to phenylephrine and impaired metacholine-induced vasodilatation when compared with littermate controls or with the doxycyline-treated group. Our studies suggest that up-regulation of this vascular chymase is sufficient to cause a hypertensive arteriopathy, and that RVCH may be a candidate gene and a therapeutic target in patients with high blood pressure.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.