Acute arterial thrombosis in the absence of inflammation: the stress-related anti-inflammatory hormone ACTH participates in platelet-mediated thrombosis
| Autor: | Monica Torres Coronado, Aranzazu Ortega Pozzi, Panayotis Fantidis, Pablo González, Esther Bernardo, Marie Anne Punchard |
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| Rok vydání: | 2008 |
| Předmět: |
Blood Platelets
endocrine system medicine.medical_specialty Time Factors Hydrocortisone Platelet Aggregation Swine Inflammation Adrenocorticotropic hormone Injections Intramuscular Receptors Purinergic P2Y2 Adrenocorticotropic Hormone Internal medicine medicine Cyclic AMP Purinergic P2 Receptor Antagonists Animals Platelet Receptor business.industry Interleukin-6 Receptors Purinergic P2 Thrombosis Disease Models Animal Endocrinology Acute Disease Platelet aggregation inhibitor Calcium medicine.symptom Cardiology and Cardiovascular Medicine business Carotid Artery Injuries hormones hormone substitutes and hormone antagonists Ex vivo Platelet Aggregation Inhibitors medicine.drug Hormone |
| Zdroj: | Atherosclerosis. 204(1) |
| ISSN: | 1879-1484 |
| Popis: | Objective Despite the reciprocal relationship that exists between inflammation and thrombosis, we asked whether thrombosis can develop without inflammation, and whether stress-related hormones (ACTH and cortisol) influence platelet-mediated thrombosis. Methods We investigated the role of ACTH and cortisol in platelet aggregation, as well as on the circulating levels of IL-6 in pigs subjected to different treatments. In control animals, deep vessel wall injury (DVWI) was induced in the right common carotid artery, while in the animals under study DVWI was induced 60min after ACTH administration (subgroup 1) or not at all (subgroup 2). In an ex vivo study we evaluated whether ACTH or cortisol modulates platelet aggregation. Indeed, we assessed whether blocking the P2Y platelet receptors inhibits the effect of ACTH on platelet aggregation. Finally, we assessed whether ACTH mobilizes intracellular calcium and modulates intracellular cAMP in platelets ex vivo . Results We found that the suppression of inflammation following ACTH administration was accompanied by acute arterial thrombosis in the zone of injury in vivo . Furthermore, ACTH but not cortisol amplifies the platelet aggregation induced ex vivo by agonists. Platelets do not express ACTH receptors which may explain why ACTH does not reduce intracellular levels of cAMP in platelets. Nevertheless, supraphysiological concentrations of ACTH increase calcium mobilization in platelets. Conclusion These results indicate for the first time that ACTH may fulfil an important role in acute arterial thrombosis by increasing the platelet aggregation induced by agonists, probably via a G q -coupled pathway. |
| Databáze: | OpenAIRE |
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