Recio Carlota, Maione Francesco, Iqbal Asif J, Mascolo Nicola, De Feo Vincenzo
Sir William Dunn School of Pathology, University of Oxford Oxford, UK.
Department of Pharmacy, University of Naples Federico II Naples, Italy.
Front Pharmacol. 2017 Jan 6;7:526. doi: 10.3389/fphar.2016.00526. eCollection 2016.
Cardiovascular disease (CVD) remains a leading cause of mortality and morbidity worldwide. Numerous therapies are currently under investigation to improve pathological cardiovascular complications, but yet, there have been very few new medications approved for intervention/treatment. Therefore, new approaches to treat CVD are urgently required. Attempts to prevent vascular complications usually involve amelioration of contributing risk factors and underlying processes such as inflammation, obesity, hyperglycaemia, or hypercholesterolemia. Historically, the development of peptides as therapeutic agents has been avoided by the Pharmaceutical industry due to their low stability, size, rate of degradation, and poor delivery. However, more recently, resurgence has taken place in developing peptides and their mimetics for therapeutic intervention. As a result, increased attention has been placed upon using peptides that mimic the function of mediators involved in pathologic processes during vascular damage. This review will provide an overview on novel targets and experimental therapeutic approaches based on peptidomimetics for modulation in CVD. We aim to specifically examine apolipoprotein A-I (apoA-I) and apoE mimetic peptides and their role in cholesterol transport during atherosclerosis, suppressors of cytokine signaling (SOCS)1-derived peptides and annexin-A1 as potent inhibitors of inflammation, incretin mimetics and their function in glucose-insulin tolerance, among others. With improvements in technology and synthesis platforms the future looks promising for the development of novel peptides and mimetics for therapeutic use. However, within the area of CVD much more work is required to identify and improve our understanding of peptide structure, interaction, and function in order to select the best targets to take forward for treatment.
心血管疾病(CVD)仍然是全球范围内导致死亡和发病的主要原因。目前有许多治疗方法正在研究中,以改善病理性心血管并发症,但获批用于干预/治疗的新药物却很少。因此,迫切需要治疗CVD的新方法。预防血管并发症的尝试通常涉及改善促成风险因素和潜在过程,如炎症、肥胖、高血糖或高胆固醇血症。从历史上看,由于肽的稳定性低、尺寸小、降解速率快和递送性差,制药行业一直避免将其开发为治疗剂。然而,最近,在开发用于治疗干预的肽及其模拟物方面出现了复兴。因此,人们越来越关注使用模拟血管损伤期间参与病理过程的介质功能的肽。本综述将概述基于拟肽调节心血管疾病的新靶点和实验性治疗方法。我们旨在具体研究载脂蛋白A-I(apoA-I)和apoE模拟肽及其在动脉粥样硬化过程中胆固醇转运中的作用、细胞因子信号转导抑制因子(SOCS)1衍生肽和膜联蛋白A1作为炎症的有效抑制剂、肠促胰岛素模拟物及其在葡萄糖-胰岛素耐受性中的功能等。随着技术和合成平台的改进,新型肽和模拟物用于治疗用途的开发前景广阔。然而,在心血管疾病领域,为了选择最佳靶点进行治疗,还需要做更多的工作来识别和加深我们对肽的结构、相互作用和功能的理解。