Klaus Veronika, Schmies Fadwa, Reeps Christian, Trenner Matthias, Geisbüsch Sarah, Lohoefer Fabian, Eckstein Hans-Henning, Pelisek Jaroslav
1 Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
2 University Centre for Vascular Medicine and Department of Vascular Surgery, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
Vasa. 2018 Jun;47(4):285-293. doi: 10.1024/0301-1526/a000701. Epub 2018 Apr 6.
Cathepsins have been described in the pathogenesis of abdominal aortic aneurysm (AAA), their exact role, especially in collagen degradation, is still unclear. The aim of the present study was therefore to analyse relevant cathepsins in human AAA tissue samples in relation to collagen I, III, and their degradation products.
Samples from 37 AAA patients obtained from elective open surgical repair and eight healthy non-aneurysmatic aortas from kidney donors were included. Expression of cathepsins B, D, K, L, S, cystatin C, collagen I and III, their degraded products C-Telopeptide of type 1 and 3 collagen (CTX-I, CTX-III), cellular markers for leukocytes (CD45), T cells (CD3), macrophage scavenger receptor-1 (MSR-1), synthetic, and contractile smooth muscle cells (SMCs) (smoothelin: SMTH, collagen I and III, myosin heavy chain: MHC, embryonic smooth muscle myosin heavy chain: SMemb) were determined at messenger RNA (mRNA) level, using SYBRGreen-based quantitative PCR and at protein level using enzyme-linked immunosorbent assay (ELISA).
Expression of cathepsins B, D, L, and S at mRNA level was significantly elevated in AAA compared to control aorta (1.7-fold, p = 0.025; 2.5-fold, p = 0.002; 2.6-fold, p = 0.034; and 7.0-fold, p = 0.003). Expression of cathepsin S correlated significantly with leukocytes and macrophages (ρ = 0.398, p = 0.033 and ρ = 0.422, p = 0.020), synthetic SMCs were significantly associated with cathepsins B, D, and L (ρ = 0.522, p = 0.003; ρ = 0.431, p = 0.015 and ρ = 0.467, p = 0.008). At protein level, cathepsins B and S were elevated in AAA compared to controls (5.4-fold, p = 0.001 and 7.3-fold, p < 0.001). Significant correlations were observed between collagen I, its degraded product, and cathepsin S (r = -0.350, p = 0.034 and r = +0.504, p < 0.001). Expression of cathepsin B was associated with SMCs, expression of cathepsin S with inflammatory cells.
Particularly cathepsin S was associated with the degradation product of collagen I and thus might be involved in the progression of AAA. Furthermore, cathepsin S correlated with inflammatory cells.
组织蛋白酶已被描述与腹主动脉瘤（AAA）的发病机制有关，但其确切作用，尤其是在胶原蛋白降解方面，仍不清楚。因此，本研究的目的是分析人类AAA组织样本中相关组织蛋白酶与I型和III型胶原蛋白及其降解产物的关系。
纳入37例接受择期开放手术修复的AAA患者的样本以及8例来自肾脏供体的健康非动脉瘤性主动脉样本。使用基于SYBRGreen的定量PCR在信使核糖核酸（mRNA）水平测定组织蛋白酶B、D、K、L、S、胱抑素C、I型和III型胶原蛋白、它们的降解产物I型和III型胶原蛋白的C末端肽（CTX-I、CTX-III）、白细胞（CD45）、T细胞（CD3）、巨噬细胞清道夫受体-1（MSR-1）、合成型和收缩型平滑肌细胞（SMC）（平滑肌肌动蛋白：SMTH、I型和III型胶原蛋白、肌球蛋白重链：MHC、胚胎平滑肌肌球蛋白重链：SMemb）的表达，并使用酶联免疫吸附测定（ELISA）在蛋白质水平进行测定。
与对照主动脉相比，AAA中组织蛋白酶B、D、L和S在mRNA水平的表达显著升高（分别为1.7倍，p = 0.025；2.5倍，p = 0.002；2.6倍，p = 0.034；和7.0倍，p = 0.003）。组织蛋白酶S的表达与白细胞和巨噬细胞显著相关（ρ = 0.398，p = 0.033和ρ = 0.422，p = 0.020），合成型SMC与组织蛋白酶B、D和L显著相关（ρ = 0.522，p = 0.003；ρ = 0.431，p = 0.015和ρ = 0.467，p = 0.008）。在蛋白质水平，与对照相比，AAA中组织蛋白酶B和S升高（分别为5.4倍，p = 0.001和7.3倍，p < 0.001）。观察到I型胶原蛋白及其降解产物与组织蛋白酶S之间存在显著相关性（r = -0.350，p = 0.034和r = +0.504，p < 0.001）。组织蛋白酶B的表达与SMC相关，组织蛋白酶S的表达与炎症细胞相关。
特别是组织蛋白酶S与I型胶原蛋白的降解产物相关，因此可能参与AAA的进展。此外，组织蛋白酶S与炎症细胞相关。
