Soleiman A, Lukschal A, Hacker S, Aumayr K, Hoetzenecker K, Lichtenauer M, Moser B, Untersmayr E, Horvat R, Ankersmit H J
Clinical Institute of Pathology, General Hospital Vienna, Medical University of Vienna, Vienna, Austria.
Eur J Clin Invest. 2008 Oct;38(10):708-12. doi: 10.1111/j.1365-2362.2008.02000.x.
Acute coronary syndrome is related to increased circulatory concentration of soluble apoptosis specific caspase-cleaved cytokeratin-18 (ccCK-18). Potential cardiac sources of this intermediate filament derivative have not been investigated to date.
Paraffin embedded tissue of normal myocardium, and chronically damaged samples of ischaemic, congestive and hypertrophic cardiomyopathy were analysed by histology and by CK-8, CK-18, ccCK-18 immunohistochemistry (each group, n = 15). Antibody specificity of the ccCK-18 antibody M30 was checked by immunoblotting on lysed myocardium and enriched myocardial lysosomes.
ccCK-18 and CK-18 but not CK-8 were present in all forms of cardiomyopathy, most prominently in ischaemic cardiomyopathy while only traces were detectable immunohistochemically in normal myocardium. Weak CK-18 and strong ccCK-18 staining co-localized to lysosomes with cardiac age pigment lipofuscin. Weak staining of CK-18 was detected in the cytoplasm of coronary endothelia.
Our study reveals that cardiac lipofuscin-laden lysosomes contain ccCK-18, a marker of apoptosis and its precursor CK-18. This ccCK-18 pool might contribute to increased systemic levels of ccCK-18 in acute coronary syndrome thus monitoring myocardial damage.
急性冠状动脉综合征与可溶性凋亡特异性半胱天冬酶切割细胞角蛋白18（ccCK - 18）循环浓度升高有关。迄今为止，尚未对这种中间丝衍生物的潜在心脏来源进行研究。
通过组织学以及CK - 8、CK - 18、ccCK - 18免疫组织化学方法（每组n = 15）分析正常心肌的石蜡包埋组织以及缺血性、充血性和肥厚性心肌病的慢性损伤样本。通过对裂解的心肌和富集的心肌溶酶体进行免疫印迹检查ccCK - 18抗体M30的抗体特异性。
ccCK - 18和CK - 18存在于所有形式的心肌病中，但CK - 8不存在，在缺血性心肌病中最为明显，而在正常心肌中免疫组化仅可检测到微量。CK - 18弱阳性和ccCK - 18强阳性染色与含有心脏老年色素脂褐素的溶酶体共定位。在冠状动脉内皮细胞的细胞质中检测到CK - 18弱阳性染色。
我们的研究表明，含有心脏脂褐素的溶酶体含有ccCK - 18，这是一种凋亡标志物及其前体CK - 18。这个ccCK - 18库可能导致急性冠状动脉综合征中ccCK - 18全身水平升高，从而监测心肌损伤。
