McChord Johanna, Pereyra Valeria Martínez, Froebel Sarah, Bekeredjian Raffi, Schwab Matthias, Ong Peter
Department of Cardiology and Angiology, Robert-Bosch-Krankenhaus, Stuttgart, Germany.
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
Front Cardiovasc Med. 2023 Jun 16;10:1156456. doi: 10.3389/fcvm.2023.1156456. eCollection 2023.
In today's era of individualized precision medicine drug repurposing represents a promising approach to offer patients fast access to novel treatments. Apart from drug repurposing in cancer treatments, cardiovascular pharmacology is another attractive field for this approach. Patients with angina pectoris without obstructive coronary artery disease (ANOCA) report refractory angina despite standard medications in up to 40% of cases. Drug repurposing also appears to be an auspicious option for this indication. From a pathophysiological point of view ANOCA patients frequently suffer from vasomotor disorders such as coronary spasm and/or impaired microvascular vasodilatation. Consequently, we carefully screened the literature and identified two potential therapeutic targets: the blockade of the endothelin-1 (ET-1) receptor and the stimulation of soluble guanylate cyclase (sGC). Genetically increased endothelin expression results in elevated levels of ET-1, justifying ET-1 receptor blockers as drug candidates to treat coronary spasm. sGC stimulators may be beneficial as they stimulate the NO-sGC-cGMP pathway leading to GMP-mediated vasodilatation.
在当今个体化精准医学时代,药物重新利用是一种很有前景的方法,能让患者快速获得新的治疗方法。除了在癌症治疗中重新利用药物外,心血管药理学是这种方法的另一个有吸引力的领域。高达40%的无阻塞性冠状动脉疾病的心绞痛(ANOCA)患者在接受标准药物治疗后仍报告难治性心绞痛。药物重新利用对于这一适应症似乎也是一个有利的选择。从病理生理学角度来看,ANOCA患者经常患有血管舒缩障碍,如冠状动脉痉挛和/或微血管舒张受损。因此,我们仔细筛选了文献,确定了两个潜在的治疗靶点:内皮素-1(ET-1)受体阻断和可溶性鸟苷酸环化酶(sGC)刺激。基因水平上内皮素表达增加会导致ET-1水平升高,这使得ET-1受体阻滞剂成为治疗冠状动脉痉挛的候选药物。sGC刺激剂可能有益,因为它们刺激NO-sGC-cGMP途径,导致GMP介导的血管舒张。