Myocardial lipofuscin-laden lysosomes contain the apoptosis marker caspase-cleaved cytokeratin-18.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Soleiman
A
A
Clinical Institute of Pathology, General Hospital Vienna, Medical University of Vienna, Vienna, Austria.
Lukschal
A
A
Hacker
S
S
Aumayr
K
K
Hoetzenecker
K
K
Lichtenauer
M
M
Moser
B
B
Untersmayr
E
E
Horvat
R
R
Ankersmit
H J
HJ
D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D006332:Cardiomegaly / Q000378:metabolism; D009202:Cardiomyopathies / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000378:metabolism; D016022:Case-Control Studies; D020169:Caspases / Q000378:metabolism; D005260:Female; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D007150:Immunohistochemistry; D053538:Keratin-18 / Q000032:analysis*; D008062:Lipofuscin / Q000378:metabolism*; D008247:Lysosomes / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure
D015415:Biomarkers; D053538:Keratin-18; D008062:Lipofuscin; D020169:Caspases