Pshezhetsky Alexey V, Hinek Aleksander
Department of Medical Genetics, CHU Sainte-Justine Research Center, Departments of Pediatrics and Biochemistry, University of Montreal, Montreal, Quebec H3T1C5, Canada.
Trends Cardiovasc Med. 2009 Jan;19(1):11-7. doi: 10.1016/j.tcm.2009.03.002.
Lysosomal carboxypeptidases play important roles in catabolism of proteins and peptides and in posttranslational processing of other lysosomal enzymes. The major lysosomal serine carboxypeptidase A (cathepsin A [CathA]), also known as protective protein, activates and stabilizes two other lysosomal enzymes, beta-galactosidase and neuraminidase/sialidase 1. Genetic deficiency of CathA (galactosialidosis) causes the lysosomal storage of sialylated glycoconjugates and leads to a multiorgan pathology. The galactosialidosis patients also show arterial hypertension and cardiomyopathy, conditions not predicted from the lysosomal storage of glycoconjugates. This review summarizes the experimental data suggesting that both cardiovascular pathologies associate with persisted vasoconstrictions and impaired formation of the elastic fibers triggered by the deficiency of CathA. We also discuss the homologous serine carboxypeptidases, Scpep1 and vitellogenic-like carboxypeptidase, that are secreted from endothelial cells and could potentially affect the cardiovascular system.
溶酶体羧肽酶在蛋白质和肽的分解代谢以及其他溶酶体酶的翻译后加工过程中发挥着重要作用。主要的溶酶体丝氨酸羧肽酶A（组织蛋白酶A [CathA]），也称为保护蛋白，可激活并稳定另外两种溶酶体酶，即β-半乳糖苷酶和神经氨酸酶/唾液酸酶1。CathA的基因缺陷（半乳糖唾液酸贮积症）会导致唾液酸化糖缀合物在溶酶体中蓄积，并引发多器官病变。半乳糖唾液酸贮积症患者还会出现动脉高血压和心肌病，这些病症并非由糖缀合物在溶酶体中的蓄积所预测。本综述总结了实验数据，表明这两种心血管病变均与CathA缺乏引发的持续性血管收缩和弹性纤维形成受损有关。我们还讨论了从内皮细胞分泌的同源丝氨酸羧肽酶Scpep1和卵黄生成样羧肽酶，它们可能会影响心血管系统。
