Depto. Fisiologia, Fac. Medicina, Universidad de Granada, 18071 Granada, Spain.
Depto. Ciencias de la salud, Universidad de Jaén, 23071 Jaén, Spain.
Int J Mol Sci. 2020 Aug 5;21(16):5615. doi: 10.3390/ijms21165615.
Aminopeptidases (APs) are metalloenzymes that hydrolyze peptides and polypeptides by scission of the N-terminus amino acid and that also participate in the intracellular final digestion of proteins. APs play an important role in protein maturation, signal transduction, and cell-cycle control, among other processes. These enzymes are especially relevant in the control of cardiovascular and renal functions. APs participate in the regulation of the systemic and local renin-angiotensin system and also modulate the activity of neuropeptides, kinins, immunomodulatory peptides, and cytokines, even contributing to cholesterol uptake and angiogenesis. This review focuses on the role of four key APs, aspartyl-, alanyl-, glutamyl-, and leucyl-cystinyl-aminopeptidases, in the control of blood pressure (BP) and renal function and on their association with different cardiovascular and renal diseases. In this context, the effects of AP inhibitors are analyzed as therapeutic tools for BP control and renal diseases. Their role as urinary biomarkers of renal injury is also explored. The enzymatic activities of urinary APs, which act as hydrolyzing peptides on the luminal surface of the renal tubule, have emerged as early predictive renal injury biomarkers in both acute and chronic renal nephropathies, including those induced by nephrotoxic agents, obesity, hypertension, or diabetes. Hence, the analysis of urinary AP appears to be a promising diagnostic and prognostic approach to renal disease in both research and clinical settings.
氨肽酶（APs）是一类金属蛋白酶，通过裂解肽和多肽的 N 端氨基酸来水解它们，并且还参与蛋白质的细胞内最终消化。APs 在蛋白质成熟、信号转导和细胞周期控制等过程中发挥着重要作用。这些酶在心血管和肾脏功能的控制中尤为重要。APs 参与了全身和局部肾素-血管紧张素系统的调节，也调节神经肽、激肽、免疫调节肽和细胞因子的活性，甚至有助于胆固醇摄取和血管生成。本综述重点介绍了四种关键的 AP，天冬氨酰、丙氨酰、谷氨酰和亮氨酰-胱氨酰氨肽酶，在控制血压（BP）和肾功能中的作用及其与不同心血管和肾脏疾病的关系。在这方面，分析了 AP 抑制剂作为控制血压和肾脏疾病的治疗工具的作用。还探讨了它们作为肾脏损伤尿生物标志物的作用。尿液 APs 的酶活性作为肾小管腔表面的水解肽，已成为急性和慢性肾肾病（包括肾毒性药物、肥胖、高血压或糖尿病引起的肾病）的早期预测性肾损伤生物标志物。因此，分析尿液 AP 似乎是研究和临床环境中肾脏疾病有前途的诊断和预后方法。
