Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
Int J Mol Sci. 2024 Aug 26;25(17):9237. doi: 10.3390/ijms25179237.
Furin is an important proteolytic enzyme, converting several proteins from inactive precursors to their active forms. Recently, proteo-genomic analyses in European and East Asian populations suggested a causal association of furin with ischaemic heart disease, and there is growing interest in its role in cardiovascular disease (CVD) aetiology. In this narrative review, we present a critical appraisal of evidence from population studies to assess furin's role in CVD risk and potential as a drug target for CVD. Whilst most observational studies report positive associations between furin expression and CVD risk, some studies report opposing effects, which may reflect the complex biological roles of furin and its substrates. Genetic variation in is also associated with CVD and its risk factors. We found no evidence of current clinical development of furin as a drug target for CVD, although several phase 1 and 2 clinical trials of furin inhibitors as a type of cancer immunotherapy have been completed. The growing field of proteo-genomics in large-scale population studies may inform the future development of furin and other potential drug targets to improve the treatment and prevention of CVD.
弗林是一种重要的蛋白水解酶，可将几种蛋白质从无活性的前体转化为其活性形式。最近，欧洲和东亚人群的蛋白质组学分析表明，弗林与缺血性心脏病之间存在因果关系，人们对其在心血管疾病（CVD）发病机制中的作用越来越感兴趣。在本综述中，我们对来自人群研究的证据进行了批判性评估，以评估弗林在 CVD 风险中的作用及其作为 CVD 药物靶点的潜力。尽管大多数观察性研究报告了弗林表达与 CVD 风险之间的正相关关系，但一些研究报告了相反的效果，这可能反映了弗林及其底物的复杂生物学作用。 中的遗传变异也与 CVD 及其危险因素相关。我们没有发现将弗林作为 CVD 药物靶点进行临床开发的当前证据，尽管已经完成了几种弗林抑制剂作为一种癌症免疫疗法的 1 期和 2 期临床试验。在大规模人群研究中，蛋白质组学领域的不断发展可能为弗林和其他潜在药物靶点的未来发展提供信息，以改善 CVD 的治疗和预防。
