ArticleBlood2022
A mechanism for hereditary angioedema caused by a lysine 311-to-glutamic acid substitution in plasminogen.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Therapeutic Targeting of the Bradykinin B2 Receptor in Immunological and Vascular Diseases: Insights from Kinin Biology to Clinical Outcomes.Clinical reviews in allergy & immunology · 2026Review
- The 2025 WAO Guidelines for the classification, diagnosis, and treatment of hereditary angioedema, with consideration of worldwide disparities.The World Allergy Organization journal · 2026Article
- The International/Canadian hereditary angioedema guideline.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2026Review
- Hereditary Angioedema with Normal C1 Inhibitor: an Updated International Consensus Paper on Diagnosis, Pathophysiology, and Treatment.Clinical reviews in allergy & immunology · 2025Review
- Factor XII Structure-Function Relationships.Seminars in thrombosis and hemostasis · 2024Review
- Hereditary Angioedema: The Clinical Picture of Excessive Contact Activation.Seminars in thrombosis and hemostasis · 2024Review
- Contactless edema via plasmin.Blood · 2024Article
- A mechanism for hereditary angioedema caused by a methionine-379-to-lysine substitution in kininogens.Blood · 2024Article
- Plasminogen missense variants and their involvement in cardiovascular and inflammatory disease.Frontiers in cardiovascular medicine · 2024Review
- High molecular weight kininogen interactions with the homologs prekallikrein and factor XI: importance to surface-induced coagulation.Journal of thrombosis and haemostasis : JTH · 2024Article
- Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.Thrombosis and haemostasis · 2023Article
- Genetic Variants Leading to Urticaria and Angioedema and Associated Biomarkers.The journal of allergy and clinical immunology. In practice · 2023Article
- C1 inhibitor deficiency enhances contact pathway-mediated activation of coagulation and venous thrombosis.Blood · 2023Article
- Titanium is a potent inducer of contact activation: implications for intravascular devices.Journal of thrombosis and haemostasis : JTH · 2023Article
- Managing Diagnosis, Treatment, and Burden of Disease in Hereditary Angioedema Patients with Normal C1-Esterase Inhibitor.Journal of asthma and allergy · 2023Review
- Mechanisms involved in hereditary angioedema with normal C1-inhibitor activity.Frontiers in physiology · 2023Review
- The complex role of kininogens in hereditary angioedema.Frontiers in allergy · 2022Review
- Mutant plasminogen in hereditary angioedema is bypassing FXII/kallikrein to generate bradykinin.Frontiers in physiology · 2022Article
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10 authors at 4 institutions in 2 countries.
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Abstract
Patients with hereditary angioedema (HAE) experience episodes of bradykinin (BK)-induced swelling of skin and mucosal membranes. The most common cause is reduced plasma activity of C1 inhibitor, the main regulator of the proteases plasma kallikrein (PKa) and factor XIIa (FXIIa). Recently, patients with HAE were described with a Lys311 to glutamic acid substitution in plasminogen (Plg), the zymogen of the protease plasmin (Plm). Adding tissue plasminogen activator to plasma containing Plg-Glu311 vs plasma containing wild-type Plg (Plg-Lys311) results in greater BK generation. Similar results were obtained in plasma lacking prekallikrein or FXII (the zymogens of PKa and FXIIa) and in normal plasma treated with a PKa inhibitor, indicating Plg-Glu311 induces BK generation independently of PKa and FXIIa. Plm-Glu311 cleaves high and low molecular weight kininogens (HK and LK, respectively), releasing BK more efficiently than Plm-Lys311. Based on the plasma concentrations of HK and LK, the latter may be the source of most of the BK generated by Plm-Glu311. The lysine analog ε-aminocaproic acid blocks Plm-catalyzed BK generation. The Glu311 substitution introduces a lysine-binding site into the Plg kringle 3 domain, perhaps altering binding to kininogens. Plg residue 311 is glutamic acid in most mammals. Glu311 in patients with HAE, therefore, represents reversion to the ancestral condition. Substantial BK generation occurs during Plm-Glu311 cleavage of human HK, but not mouse HK. Furthermore, mouse Plm, which has Glu311, did not liberate BK from human kininogens more rapidly than human Plg-Lys311. This indicates Glu311 is pathogenic in the context of human Plm when human kininogens are the substrates.
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