ArticleThe Journal of clinical investigation2005
Arterial and renal consequences of partial genetic deficiency in tissue kallikrein activity in humans.
Article in The Journal of clinical investigation, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 68 citations in OpenAlex.
- Endothelial triple-pathway vasorelaxation as an adjunctive strategy in resistant hypertension.Journal of hypertension · 2026Review
- Kinin receptors in adipose tissue: drivers of inflammation and metabolic dysfunction in obesity.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Searching for Genetic Biomarkers for Hereditary Angioedema Due to C1-Inhibitor Deficiency (C1-INH-HAE).Frontiers in allergy · 2022Article
- Kinins and Kinin Receptors in Cardiovascular and Renal Diseases.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Role of Kinins in Hypertension and Heart Failure.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Novel risk genes and mechanisms implicated by exome sequencing of 2572 individuals with pulmonary arterial hypertension.Genome medicine · 2019Article
- Evaluation of a crystallographic surrogate for kallikrein 5 in the discovery of novel inhibitors for Netherton syndrome.Acta crystallographica. Section F, Structural biology communications · 2019Article
- Human tissue kallikrein in the treatment of acute ischemic stroke.Therapeutic advances in neurological disorders · 2019Review
- Kallikrein/K1, Kinins, and ACE/Kininase II in Homeostasis and in Disease Insight From Human and Experimental Genetic Studies, Therapeutic Implication.Frontiers in medicine · 2019Review
- Article
- Serine Protease Activation Essential for Endothelial-Mesenchymal Transition in Vascular Calcification.Circulation research · 2015Article
- Unleashing the therapeutic potential of human kallikrein-related serine proteases.Nature reviews. Drug discovery · 2015Review
- A new look at electrolyte transport in the distal tubule.Annual review of physiology · 2012Review
- Effects of protein coding polymorphisms in the kallikrein 1 gene on baseline blood pressure and antihypertensive response to irbesartan in Chinese hypertensive patients.Journal of human hypertension · 2011Article
- The kallikrein-kinin system as a regulator of cardiovascular and renal function.Comprehensive Physiology · 2011Review
- Tissue kallikrein is essential for invasive capacity of circulating proangiogenic cells.Circulation research · 2011Article
- Critical role of tissue kallikrein in vessel formation and maturation: implications for therapeutic revascularization.Arteriosclerosis, thrombosis, and vascular biology · 2009Article
- Tissue kallikrein stimulates Ca(2+) reabsorption via PKC-dependent plasma membrane accumulation of TRPV5.The EMBO journal · 2006Article
- Vascular remodeling and the kallikrein-kinin system.The Journal of clinical investigation · 2005Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue kallikrein (TK), the major kinin-forming enzyme, is synthesized in several organs, including the kidney and arteries. A loss-of-function polymorphism of the human TK gene (R53H) induces a substantial decrease in enzyme activity. As inactivation of the TK gene in the mouse induces endothelial dysfunction, we investigated the vascular, hormonal, and renal phenotypes of carriers of the 53H allele. In a crossover study, 30 R53R-homozygous and 10 R53H-heterozygous young normotensive white males were randomly assigned to receive both a low sodium-high potassium diet to stimulate TK synthesis and a high sodium-low potassium diet to suppress TK synthesis, each for 1 week. Urinary kallikrein activity was 50-60% lower in R53H subjects than in R53R subjects. Acute flow-dependent vasodilatation and endothelium-independent vasodilatation of the brachial artery were both unaffected in R53H subjects. In contrast, R53H subjects consistently exhibited an increase in wall shear stress and a paradoxical reduction in artery diameter and lumen compared with R53R subjects. Renal and hormonal adaptation to diets was unaffected in R53H subjects. The partial genetic deficiency in TK activity is associated with an inward remodeling of the brachial artery, which is not adapted to a chronic increase in wall shear stress, indicating a new form of arterial dysfunction affecting 5-7% of white people.
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