Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
The Valley Hospital, Ridgewood, NJ, USA.
Cardiovasc Res. 2017 Jul 1;113(8):849-857. doi: 10.1093/cvr/cvx092.
Heart valve diseases (HVDs) arise from a number of different processes that affect both the structure and function of the valve apparatus. Despite diverse aetiologies, treatments for HVDs are limited to percutaneous or surgical interventions. The search for medical therapies to prevent or slow the progression of HVDs has been hampered by our poor understanding of the progression from subclinical to symptomatic phases, and our limited knowledge of the molecular signals that control the susceptibility of valve interstitial cells to pathological remodeling. Clinical evidence has suggested a link between certain neurotransmitters and valvular diseases of the heart. The fenfluramine-phentermine appetite suppressants popular in the 1980s were linked to mitral valve dysfunction, and ergot-derived dopamine agonists for Parkinson's disease have been associated with an increased risk of mitral and aortic valve regurgitation. The effect does not appear to be limited to medications, as valvular pathologies have also been observed in patients with carcinoid tumours of serotonin-producing enterochromaffin cells. The role of neurotransmitter molecules in valve pathology has not been adequately characterized and may represent a target for future medical therapies. Here we present current evidence from both clinical and basic science suggesting a link between neurotransmitters and HVDs, opening the door to future research in this area.
心脏瓣膜病(HVD)源于多种不同的过程,这些过程会影响瓣膜装置的结构和功能。尽管病因多种多样,但 HVD 的治疗方法仅限于经皮或手术干预。由于我们对从亚临床到有症状阶段的进展了解甚少,以及我们对控制瓣膜间质细胞易患病理性重塑的分子信号的了解有限,因此,寻找预防或减缓 HVD 进展的医学疗法一直受到阻碍。临床证据表明某些神经递质与心脏的瓣膜疾病之间存在关联。20 世纪 80 年代流行的芬氟拉明-苯丙胺食欲抑制剂与二尖瓣功能障碍有关,而用于治疗帕金森病的麦角衍生多巴胺激动剂与二尖瓣和主动脉瓣反流的风险增加有关。这种影响似乎不仅限于药物,因为在产生血清素的肠嗜铬细胞类癌肿瘤患者中也观察到了瓣膜病变。神经递质分子在瓣膜病理学中的作用尚未得到充分描述,可能是未来医学治疗的一个靶点。在这里,我们从临床和基础科学两个方面提供了当前的证据,表明神经递质与 HVD 之间存在关联,为该领域的未来研究开辟了道路。