ArticleProceedings of the National Academy of Sciences of the United States of America2014
Mutation of Plekha7 attenuates salt-sensitive hypertension in the rat.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- 2015 Guidelines for Establishing Genetically Modified Rat Models for Cardiovascular Research.Journal of cardiovascular translational research · 2015Guideline
- Broiler Ascites Syndrome as a Potential Spontaneous Animal Model for Human Pulmonary Arterial Hypertension: A Narrative Review.Life (Basel, Switzerland) · 2026Review
- INSIG1 parallel substitution drives lipid/sterol metabolic plasticity mediating desert adaptation in ungulates.Communications biology · 2026Article
- Genome-wide scan for selection signatures reveals novel insights into the adaptive capacity characteristics in three Chinese cattle breeds.BMC genomics · 2025Article
- Spontaneous vascular dysfunction in Dahl salt-sensitive male rats raised without a high-salt diet.Physiological reports · 2024Article
- Genetic Modifications to Alter Blood Pressure Level.Biomedicines · 2022Review
- Accelerated lysine metabolism conveys kidney protection in salt-sensitive hypertension.Nature communications · 2022Article
- Pathophysiology and genetics of salt-sensitive hypertension.Frontiers in physiology · 2022Review
- Origin and Evolution of the Multifaceted Adherens Junction Component Plekha7.Frontiers in cell and developmental biology · 2022Article
- PLEKHA7 signaling is necessary for the growth of mutant KRAS driven colorectal cancer.Experimental cell research · 2021Article
- Salt-Sensitive Hypertension, Renal Injury, and Renal Vasodysfunction Associated With Dahl Salt-Sensitive Rats Are Abolished in Consomic SS.BN1 Rats.Journal of the American Heart Association · 2021Article
- Loss of Chloride Channel 6 (CLC-6) Affects Vascular Smooth Muscle Contractility and Arterial Stiffness via Alterations to Golgi Calcium Stores.Hypertension (Dallas, Tex. : 1979) · 2021Article
- Sept8/SEPTIN8 involvement in cellular structure and kidney damage is identified by genetic mapping and a novel human tubule hypoxic model.Scientific reports · 2021Article
- Therapeutic genome editing in cardiovascular diseases.Advanced drug delivery reviews · 2021Review
- Spermine-Related DNA Hypermethylation and Elevated Expression of Genes for Collagen Formation are Susceptible Factors for Chemotherapy-Induced Hand-Foot Syndrome in Chinese Colorectal Cancer Patients.Frontiers in pharmacology · 2021Article
- Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.Journal of biomedical science · 2020Review
- Cooperative binding of the tandem WW domains of PLEKHA7 to PDZD11 promotes conformation-dependent interaction with tetraspanin 33.The Journal of biological chemistry · 2020Article
- Using Genetic and Species Diversity to Tackle Kidney Disease.Trends in genetics : TIG · 2020Review
- Will the real Dahl S rat please stand up?American journal of physiology. Renal physiology · 2019Article
- Human genotyping and an experimental model reveal NPR-C as a possible contributor to morbidity in coarctation of the aorta.Physiological genomics · 2019Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
PLEKHA7 (pleckstrin homology domain containing family A member 7) has been found in multiple studies as a candidate gene for human hypertension, yet functional data supporting this association are lacking. We investigated the contribution of this gene to the pathogenesis of salt-sensitive hypertension by mutating Plekha7 in the Dahl salt-sensitive (SS/JrHsdMcwi) rat using zinc-finger nuclease technology. After four weeks on an 8% NaCl diet, homozygous mutant rats had lower mean arterial (149 ± 9 mmHg vs. 178 ± 7 mmHg; P < 0.05) and systolic (180 ± 7 mmHg vs. 213 ± 8 mmHg; P < 0.05) blood pressure compared with WT littermates. Albumin and protein excretion rates were also significantly lower in mutant rats, demonstrating a renoprotective effect of the mutation. Total peripheral resistance and perivascular fibrosis in the heart and kidney were significantly reduced in Plekha7 mutant animals, suggesting a potential role of the vasculature in the attenuation of hypertension. Indeed, both flow-mediated dilation and endothelium-dependent vasodilation in response to acetylcholine were improved in isolated mesenteric resistance arteries of Plekha7 mutant rats compared with WT. These vascular improvements were correlated with changes in intracellular calcium handling, resulting in increased nitric oxide bioavailability in mutant vessels. Collectively, these data provide the first functional evidence that Plekha7 may contribute to blood pressure regulation and cardiovascular function through its effects on the vasculature.
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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 Socratic graph.