Vedantham Srinivasan, Kluever Anna-Kristina, Deindl Elisabeth
MedGenome Labs Ltd., Bangalore, Karnataka 560099, India.
School of Chemical Biotechnology, SASTRA University, Thanjavur 613401, India.
Cells. 2018 Oct 22;7(10):181. doi: 10.3390/cells7100181.
Cardiovascular diseases (CVD) are still the prevailing cause of death not only in industrialized countries, but even worldwide. Type 2 diabetes mellitus (type 2 DM) and hyperlipidemia, a metabolic disorder that is often associated with diabetes, are major risk factors for developing CVD. Recently, clinical trials proved the safety of gliptins in treating patients with type 2 DM. Gliptins are dipeptidyl-peptidase 4 (DPP4/CD26) inhibitors, which stabilize glucagon-like peptide-1 (GLP-1), thereby increasing the bioavailability of insulin. Moreover, blocking DPP4 results in increased levels of stromal cell derived factor 1 (SDF-1). SDF-1 has been shown in pre-clinical animal studies to improve heart function and survival after myocardial infarction, and to promote arteriogenesis, the growth of natural bypasses, compensating for the function of an occluded artery. Clinical trials, however, failed to demonstrate a superiority of gliptins compared to placebo treated type 2 DM patients in terms of cardiovascular (CV) outcomes. This review highlights the function of DPP4 inhibitors in type 2 DM, and in treating cardiovascular diseases, with special emphasis on arteriogenesis. It critically addresses the potency of currently available gliptins and gives rise to hope by pointing out the most relevant questions that need to be resolved.
心血管疾病（CVD）不仅是工业化国家，甚至是全球范围内主要的死亡原因。2型糖尿病（2型DM）和高脂血症（一种常与糖尿病相关的代谢紊乱）是发生CVD的主要危险因素。最近，临床试验证明了格列汀类药物治疗2型糖尿病患者的安全性。格列汀类药物是二肽基肽酶4（DPP4/CD26）抑制剂，可稳定胰高血糖素样肽-1（GLP-1），从而提高胰岛素的生物利用度。此外，阻断DPP4会导致基质细胞衍生因子1（SDF-1）水平升高。临床前动物研究表明，SDF-1可改善心肌梗死后的心功能和生存率，并促进动脉生成，即自然旁路的生长，以代偿闭塞动脉的功能。然而，临床试验未能证明与安慰剂治疗的2型糖尿病患者相比，格列汀类药物在心血管（CV）结局方面具有优势。本综述重点介绍了DPP4抑制剂在2型糖尿病和治疗心血管疾病中的作用，特别强调了动脉生成。它批判性地探讨了现有格列汀类药物的效力，并通过指出需要解决的最相关问题带来了希望。
