组织蛋白酶S与腹主动脉瘤Ⅰ型胶原降解有关。

PubMed ID
发表日期 2018年Jun月

原始出处 瓦萨。Zeitschrift fur Gefasskrankheiten公司
VASA. Zeitschrift fur Gefasskrankheiten
作者 Klaus  Veronika  Schmies  Fadwa  Reeps  Christian  Trenner  Matthias  Geisbüsch  Sarah  Lohoefer  Fabian  Eckstein  Hans-Henning  Pelisek  Jaroslav 

文献标题 组织蛋白酶S与腹主动脉瘤Ⅰ型胶原降解有关。
Cathepsin S is associated with degradation of collagen I in abdominal aortic aneurysm.

文献摘要 BACKGROUND

组织蛋白酶在腹主动脉瘤(AAA)的发病机制中已有报道,其确切作用,尤其是在胶原降解中的作用尚不清楚。因此,本研究的目的是分析人AAA组织样本中与Ⅰ、Ⅲ型胶原及其降解产物相关的组织蛋白酶。

MATERIALS AND METHODS

从37例择期开放性手术修复的AAA患者和8例来自肾供体的健康非动脉瘤性主动脉样本被纳入研究。组织蛋白酶B、D、K、L、S、胱抑素C、I型和III型胶原及其降解产物C-端肽1型和3型胶原(CTX-I、CTX-III)、白细胞标记物(CD45)、T细胞(CD3)、巨噬细胞清道夫受体-1(MSR-1)、合成的和可收缩的平滑肌细胞(SMCs)(平滑蛋白:SMTH、I型和III型胶原、肌球蛋白)重链:MHC,胚胎平滑肌肌球蛋白重链:SMemb)分别在信使RNA(mRNA)水平、SYBRGreen定量PCR和酶联免疫吸附试验(ELISA)蛋白水平检测。

RESULTS

组织蛋白酶B、D、L和S在mRNA水平的表达在AAA中显著高于对照主动脉(1.7倍,p=0.025;2.5倍,p=0.002;2.6倍,p=0.034;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),合成平滑肌细胞与组织蛋白酶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,组织蛋白酶B和S在AAA组较对照组升高(5.4倍,p=0.001和7.3倍,p<0.001)。Ⅰ型胶原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的表达与平滑肌细胞有关,组织蛋白酶S的表达与炎症细胞有关。

CONCLUSIONS

尤其是组织蛋白酶S与Ⅰ型胶原降解产物有关,因此可能参与AAA的进展。组织蛋白酶S与炎症细胞相关。


BACKGROUND

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.

MATERIALS AND METHODS

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).

RESULTS

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.

CONCLUSIONS

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.


获取全文 10.1024/0301-1526/a000701