ArticleThe Journal of clinical investigation2020
Salt causes aging-associated hypertension via vascular Wnt5a under Klotho deficiency.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- Klotho Deficiency Impairs Distal Potassium Homeostasis Through mTORC1-Dependent Suppression of ROMK.Acta physiologica (Oxford, England) · 2026Article
- High-salt diet modulates endocrine regulation between cortisol and FGF23.Pflugers Archiv : European journal of physiology · 2026Article
- Sex differences in the progression of salt-sensitive hypertension in aged Dahl salt-sensitive rats.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Article
- Ethnomedicinal Uses, Phytochemistry and Bioactivities of Halophytes and Salt-Tolerant Plants with Potential Against Metabolic Syndrome: A Comprehensive Review.Marine drugs · 2026Review
- Research progress on blood therapy for anti-aging.Journal of advanced research · 2026Review
- Novel Advances in Our Understanding of Sex-Dependent Control of Blood Pressure.Annual review of physiology · 2026Review
- Integrated mechanisms linking sodium-potassium imbalance to salt-sensitive hypertension.Physiological reports · 2025Review
- Microfluidic chip-integrated vascularized endometrial complexes: Mitochondrial function and paracrine crosstalk enhance regenerative potential.Bioactive materials · 2025Article
- Epigenetic mechanisms of salt-sensitive hypertension.Clinical kidney journal · 2025Review
- Beyond the kidney: ATRAP and the skin renin-angiotensin system in hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- Epigenetic histone modifications in kidney disease and epigenetic memory.Clinical and experimental nephrology · 2025Review
- Elevated uric acid induces erectile dysfunction in rats by interacting with MLCK and inhibiting its ubiquitin-mediated degradation.Communications biology · 2025Article
- Klotho plasma levels are an independent predictorof mortality in women with acute coronary syndrome.Scientific reports · 2025Article
- Article
- Vascular inflammaging: Endothelial CEACAM1 expression is upregulated by TNF-α via independent activation of NF-κB and β-catenin signaling.Aging cell · 2025Article
- Aging and sex differences in salt sensitivity of blood pressure.Clinical science (London, England : 1979) · 2025Review
- Klotho Protein: A Multifaceted Guardian of Healthy Aging and Its Therapeutic Potential.International journal of nanomedicine · 2025Review
- The immune-microbiome axis in salt-sensitive hypertension: a focus on renal and neural mechanisms.Frontiers in physiology · 2025Review
- NSAID use may decrease serum Klotho levels.Frontiers in endocrinology · 2025Article
- Association of serum Klotho with tinnitus prevalence, duration and severity: A cross-sectional study in middle-aged and older adults.PloS one · 2025Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aging is associated with a high prevalence of hypertension due to elevated susceptibility of BP to dietary salt, but its mechanism is unknown. Serum levels of Klotho, an anti-aging factor, decline with age. We found that high salt (HS) increased BP in aged mice and young heterozygous Klotho-knockout mice and was associated with increased vascular expression of Wnt5a and p-MYPT1, which indicate RhoA activity. Not only the Wnt inhibitor LGK974 and the Wnt5a antagonist Box5 but Klotho supplementation inhibits HS-induced BP elevation, similarly to the Rho kinase inhibitor fasudil, associated with reduced p-MYPT1 expression in both groups of mice. In cultured vascular smooth muscle cells, Wnt5a and angiotensin II (Ang II) increased p-MYPT1 expression but knockdown of Wnt5a with siRNA abolished Ang II-induced upregulation of p-MYPT1, indicating that Wnt5a is indispensable for Ang II-induced Rho/ROCK activation. Notably, Klotho inhibited Wnt5a- and Ang II-induced upregulation of p-MYPT1. Consistently, Klotho supplementation ameliorated HS-induced augmentation of reduced renal blood flow (RBF) response to intra-arterial infusion of Ang II and the thromboxane A2 analog U46619, which activated RhoA in both groups of mice and were associated with the inhibition of BP elevation, suggesting that abnormal response of RBF to Ang II contributes to HS-induced BP elevation. Thus, Klotho deficiency underlies aging-associated salt-sensitive hypertension through vascular non-canonical Wnt5a/RhoA activation.
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