ArticleJournal of thrombosis and haemostasis : JTH2010
Cleaved high molecular weight kininogen inhibits tube formation of endothelial progenitor cells via suppression of matrix metalloproteinase 2.
Article in Journal of thrombosis and haemostasis : JTH, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 26 citations in OpenAlex.
- The Kallikrein-Kinin System: Proteolytic Orchestrators of Tissue Barrier Disruption in Inflammation and Cancer.International journal of molecular sciences · 2026Review
- FBXW7 suppresses gastric cancer development and progression via ubiquitination-mediated degradation of MMP2.Frontiers in immunology · 2026Article
- Anti-HK antibody inhibits the plasma contact system by blocking prekallikrein and factor XI activation in vivo.Blood advances · 2023Article
- Anti-HK antibody reveals critical roles of a 20-residue HK region for Aβ-induced plasma contact system activation.Blood advances · 2022Article
- Intratracheal transplantation of endothelial progenitor cells attenuates smoking-induced COPD in mice.International journal of chronic obstructive pulmonary disease · 2017Article
- Hyperhomocysteinemia suppresses bone marrow CD34+/VEGF receptor 2+ cells and inhibits progenitor cell mobilization and homing to injured vasculature-a role of β1-integrin in progenitor cell migration and adhesion.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Contact pathway of coagulation and inflammation.Thrombosis journal · 2015Article
- Kallikrein-kinin in stem cell therapy.World journal of stem cells · 2014Review
- Novel role of kallistatin in vascular repair by promoting mobility, viability, and function of endothelial progenitor cells.Journal of the American Heart Association · 2014Article
- Endothelial colony-forming cells derived from pregnancies complicated by intrauterine growth restriction are fewer and have reduced vasculogenic capacity.The Journal of clinical endocrinology and metabolism · 2013Article
- Article
- Role of plasma kallikrein-kinin system activation in synovial recruitment of endothelial progenitor cells in experimental arthritis.Arthritis and rheumatism · 2012Article
- Anti-angiogenic and tumor-suppressive roles of candidate tumor-suppressor gene, Fibulin-2, in nasopharyngeal carcinoma.Oncogene · 2012Article
- Cleaved high-molecular-weight kininogen accelerates the onset of endothelial progenitor cell senescence by induction of reactive oxygen species.Arteriosclerosis, thrombosis, and vascular biology · 2011Article
- Highly selective hydrolysis of kinins by recombinant prolylcarboxypeptidase.Biochemical and biophysical research communications · 2011Article
- Targeting stem cell niches and trafficking for cardiovascular therapy.Pharmacology & therapeutics · 2011Review
- A Novel Category of Anti-Hypertensive Drugs for Treating Salt-Sensitive Hypertension on the Basis of a New Development Concept.Pharmaceuticals (Basel, Switzerland) · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
BACKGROUND AND
objectiveEndothelial progenitor cells (EPCs) contribute to postnatal neovascularization, thus promoting wide interest in their therapeutic potential in vascular injury and prevention of their dysfunction in cardiovascular diseases. Cleaved high molecular weight kininogen (HKa), an activation product of the plasma kallikrein-kinin system (KKS), inhibits the functions of differentiated endothelial cells including in vitro and in vivo angiogenesis. In this study, our results provided the first evidence that HKa is able to target EPCs and inhibits their tube forming capacity. METHODS AND
resultsWe determined the effect of HKa on EPCs using a three-dimensional vasculogenesis assay. Upon stimulation with vascular endothelial growth factor (VEGF) alone, EPCs formed vacuoles and tubes, and differentiated into capillary-like networks. As detected by gelatinolytic activity assay, VEGF stimulated secretion and activation of matrix metallopeptidase 2 (MMP-2), but not MMP-9, in the conditioned medium of 3D culture of EPCs. Specific inhibition or gene ablation of MMP-2, but not MMP-9, blocked the vacuole and tube formation by EPCs. Thus, MMP-2 is selectively required for EPC vasculogenesis. In a concentration-dependent manner, HKa significantly inhibited tube formation by EPCs and the conversion of pro-MMP-2 to MMP-2. Moreover, HKa completely blocked the association between pro-MMP-2 and alphavbeta3 integrin, and its inhibition of MMP-2 activation was dependent on the presence of alphavbeta3 integrin. In a purified system, HKa did not directly inhibit MMP-2 activity.
conclusionsHKa inhibits tube forming capacity of EPCs by suppression of MMP-2 activation, which may constitute a novel link between activation of the KKS and EPC dysfunction.
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.