ArticleArteriosclerosis, thrombosis, and vascular biology2009
Critical role of tissue kallikrein in vessel formation and maturation: implications for therapeutic revascularization.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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.
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Who cites it
34 citing papers in PubMed, 72 citations in OpenAlex.
- Human urinary kallidinogenase or edaravone combined with butylphthalide in the treatment of acute ischemic stroke.Brain and behavior · 2019Trial
- Endothelial triple-pathway vasorelaxation as an adjunctive strategy in resistant hypertension.Journal of hypertension · 2026Review
- Drug Discovery Strategies for Kallikrein-Related Peptidases.International journal of molecular sciences · 2025Review
- Article
- Proteomics analysis of aqueous and vitreous humor in uveitis: a systematic literature review.Clinical proteomics · 2025Review
- Integrating endothelium-derived hyperpolarization, nitric oxide, and prostacyclin pathways: the multimodal potential of human tissue kallikrein-1.Vascular biology (Bristol, England) · 2025Review
- Defining the clinical validity of genes reported to cause pulmonary arterial hypertension.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- Kinins and Kinin Receptors in Cardiovascular and Renal Diseases.Pharmaceuticals (Basel, Switzerland) · 2021Review
- The role of genomics and genetics in pulmonary arterial hypertension.Global cardiology science & practice · 2020Review
- Novel risk genes and mechanisms implicated by exome sequencing of 2572 individuals with pulmonary arterial hypertension.Genome medicine · 2019Article
- 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
- Effect of HUK on the outcome of ruptured intracranial aneurysm.Brain and behavior · 2018Article
- Human Urinary Kallidinogenase decreases recurrence risk and promotes good recovery.Brain and behavior · 2018Article
- Human Urinary kallidinogenase promotes good recovery in ischemic stroke patients with level 3 hypertension.Brain and behavior · 2017Article
- Danhong injection reduces vascular remodeling and up-regulates the Kallikrein-kinin system in spontaneously hypertensive rats.Scientific reports · 2017Article
- Differential regulation of blood flow-induced neovascularization and mural cell recruitment by vascular endothelial growth factor and angiopoietin signalling.The Journal of physiology · 2017Article
- Moving Past Anti-VEGF: Novel Therapies for Treating Diabetic Retinopathy.International journal of molecular sciences · 2016Review
- Article
- Involvement of Kallikrein-Related Peptidases in Normal and Pathologic Processes.Disease markers · 2015Review
- B1 but not B2 bradykinin receptor agonists promote DU145 prostate cancer cell proliferation and migration.African health sciences · 2014Article
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Authors and funding
20 authors at 1 institution in 4 countries.
Funding
Abstract
objectiveHuman Tissue Kallikrein (hKLK1) overexpression promotes an enduring neovascularization of ischemic tissue, yet the cellular mechanisms of hKLK1-induced arteriogenesis remain unknown. Furthermore, no previous study has compared the angiogenic potency of hKLK1, with its loss of function polymorphic variant, rs5515 (R53H), which possesses reduced kinin-forming activity. METHODS AND
resultsHere, we demonstrate that tissue kallikrein knockout mice (KLK1-/-) show impaired muscle neovascularization in response to hindlimb ischemia. Gene-transfer of wild-type Ad.hKLK1 but not Ad.R53H-hKLK1 was able to rescue this defect. Similarly, in the rat mesenteric assay, Ad.hKLK1 induced a mature neovasculature with increased vessel diameter through kinin-B2 receptor-mediated recruitment of pericytes and vascular smooth muscle cells, whereas Ad.R53H-hKLK1 was ineffective. Moreover, hKLK1 but not R53H-hKLK1 overexpression in the zebrafish induced endothelial precursor cell migration and vascular remodeling. Furthermore, Ad.hKLK1 activates metalloproteinase (MMP) activity in normoperfused muscle and fails to promote reparative neovascularization in ischemic MMP9-/- mice, whereas its proarteriogenic action was preserved in ApoE-/- mice, an atherosclerotic model of impaired angiogenesis.
conclusionsThese results demonstrate the fundamental role of endogenous Tissue Kallikrein in vascular repair and provide novel information on the cellular and molecular mechanisms responsible for the robust arterialization induced by hKLK1 overexpression.
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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.