Characterisation of vasodilatory responses in the presence of the CGRP receptor antibody erenumab in human isolated arteries
| Autor: | Alejandro Labastida-Ramírez, van den Bogaerdt A, Josefin Snellman, Ah Jan Danser, Cen Xu, Antoinette MaassenVanDenBrink, Clemens M F Dirven, Kristian Agmund Haanes, Eloísa Rubio-Beltrán, Ad J.J.C. Bogers |
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| Přispěvatelé: | Cardiothoracic Surgery, Neurosurgery, Internal Medicine |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Calcitonin Gene-Related Peptide Vasodilator Agents Peptide Vasodilation Calcitonin gene-related peptide Pharmacology Antibodies Monoclonal Humanized 03 medical and health sciences 0302 clinical medicine Organ Culture Techniques Calcitonin Gene-Related Peptide Receptor Antagonists medicine Humans Mammary Arteries 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology Dose-Response Relationship Drug business.industry Trigeminovascular system General Medicine Middle Aged medicine.disease Coronary Vessels Coronary arteries medicine.anatomical_structure Migraine chemistry Calcitonin biology.protein Female Neurology (clinical) Antibody business 030217 neurology & neurosurgery Receptors Calcitonin Gene-Related Peptide |
| Zdroj: | Cephalalgia. SAGE Publications Ltd |
| ISSN: | 0333-1024 |
| Popis: | Background Migraine is associated with activation of the trigeminovascular system, release of calcitonin gene-related peptide (CGRP) and dilation of dural arteries. Novel treatments target calcitonin gene-related peptide or its receptor, which are present in all vascular beds, raising cardiovascular concerns. Erenumab is a human CGRP-receptor antibody approved for the prophylactic treatment of migraine. Methods We characterised the relaxant responses to CGRP in the absence and presence of erenumab (1 μM) in isolated human middle meningeal, internal mammary and (proximal and distal) coronary arteries. Furthermore, in human internal mammary arteries from cardiovascularly-compromised patients, we assessed the pharmacological specificity of erenumab by investigating whether the vasodilatory responses to acetylcholine, sodium nitroprusside, pituitary adenylate cyclase activating polypeptide-38 (PACAP), vasoactive intestinal peptide and nicardipine, along with the vasoconstrictor responses to dihydroergotamine, were modified by erenumab. Results Calcitonin gene-related peptide induced concentration-dependent vasodilatory responses in all vessels studied that were significantly antagonised by erenumab. In human internal mammary arteries from cardiovascularly-compromised patients, the responses to acetylcholine, sodium nitroprusside, PACAP, vasoactive intestinal peptide, nicardipine and dihydroergotamine were unaffected by erenumab. Conclusion Erenumab inhibits calcitonin gene-related peptide-induced vasodilatory responses in human middle meningeal arteries, human internal mammary arteries and human coronary arteries. Moreover, erenumab shows functional specificity as no interaction was observed with the relaxant responses to several vasodilators, nor the dihydroergotamine-dependent vasoconstrictor responses. |
| Databáze: | OpenAIRE |
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