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Novel role of puberty onset protein kisspeptin as an anticoagulation peptide
Irfan Zia Qureshi1, Sobia Kanwal
1Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. irfanzia@aqau.edu.pk
Abstract:
A peptide mainly of hypothalamus and placental origin named 'kisspeptin' suppresses metastasis of melanoma cells. As several malignant tumors lead to impaired blood coagulation, we hypothesized if kisspeptin acts also as a potential anticoagulant. The effect was studied in vivo through intraperitoneal administration of kisspeptin to laboratory rats, and application of kisspeptin ex vivo to rat and human blood. In another set of experiments, clotting factors in the form of rat fresh plasma were injected into rats' prior to kisspeptin administration. Standard anticoagulation parameters were studied through established methods and commercially available kits. Herein, we demonstrate dose-dependent anticoagulation effect following in vivo kisspeptin administration. Coagulation time, bleeding time, prothrombin time and activated partial thromboplastin time were significantly (P < 0.0002) prolonged, international normalized ratio increased, while plasma calcium concentration and mean platelet count were significantly decreased (P < 0.001). Mean platelet volume increased only at the highest tested dose while platelet distribution width remained unaltered. Where fresh plasma was administered prior to kisspeptin treatment, results were similar to kisspeptin alone treatment except for significantly (P < 0.001) increased plasma calcium concentration. Application of kisspeptin ex vivo to rat and human blood produced similar results. This is the first report on kisspeptin's role in the anticoagulation of blood and suggests that it may increase the bleeding tendency possibly via modulation of calcium-signaling or inactivating calcium action, inhibition of thrombin and quick reduction in platelet numbers. A detailed investigation of the anticoagulation role of kisspeptin would help to clarify its use as an anticoagulant and thrombolytic agent.
Insights
Kisspeptin, a peptide hormone, demonstrates a dose-dependent anticoagulant effect, prolonging clotting and bleeding times. This suggests kisspeptin may increase bleeding tendency, warranting further investigation as a potential anticoagulant agent.
Area of Science:
- Endocrinology
- Hematology
- Oncology
Background:
- Kisspeptin, a peptide hormone primarily from the hypothalamus and placenta, is known to suppress melanoma metastasis.
- Malignant tumors often cause impaired blood coagulation, raising questions about kisspeptin's potential anticoagulant properties.
Purpose of the Study:
- To investigate the potential anticoagulant effects of kisspeptin.
- To determine if kisspeptin influences standard coagulation parameters and platelet counts.
Main Methods:
- Kisspeptin was administered in vivo to rats and ex vivo to rat and human blood.
- Standard anticoagulation parameters (coagulation time, bleeding time, PT, aPTT, INR) and platelet metrics were measured.
- Experiments included administration of fresh plasma prior to kisspeptin treatment.
Main Results:
- Kisspeptin administration resulted in a dose-dependent prolongation of coagulation and bleeding times.
- Prothrombin time, activated partial thromboplastin time, and international normalized ratio were significantly altered.
- Plasma calcium concentration and mean platelet count significantly decreased, while mean platelet volume increased at the highest dose.
Conclusions:
- Kisspeptin exhibits significant anticoagulation effects in vitro and in vivo.
- The findings suggest kisspeptin may increase bleeding tendency, potentially by affecting calcium signaling, thrombin activity, or platelet numbers.
- Further research into kisspeptin's anticoagulation role could clarify its potential as an anticoagulant and thrombolytic agent.
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