| Research Abstract |
Fas and Fas ligand (Fas-L) are cell-surface proteins and representative apoptosis-signaling molecules. Fas on the cell membrane induces apoptosis when it binds Fas-L or sFas-L.However, plasma sEas, a molecule lacking the transmembrane domain of Fas, blockes apoptosis by inhibiting binding between Far and Fas-L on the cell membrane. We found elevated levels of plasma soluble Far (sEas), according to the grade of NYHA in the patient with conjestive heart failure (CHF). But an increase in plasma sFas-ligand was not observed.
As apoptosis plays an important role on the progression of CHE and sFas is an inhibitor of apoptosis, we postulated that the patients with high plasma sFas have better progrnosis than those with normal plasma sFas in severe congestive heart failure of NYHA IV.
Survival rates for 6 months and 1 year were 68% and 64% in a high sPas group (over 3.7ng/mL, mean+2SD of normal subjects), and 1.4% and 11% in a normal sFas group (below 3.7ng/mL), respectively. The prognosis of severe CHF patients was definitely better in the high sFas group than in the normal sFas group (p<0.01).
In addition, we reported that 1) so-called apoptotic myocytes in the infarct area presenting positive TUNEL and DNA ladder are ultrastructurally oncotic (necrotic) myocytes with DNA fragmentation 2) disappearance of interstitial cells after myocardial infarction is due to apoptosis 3) all of TUNEL-positive myocytes in DCM simultaneously expressed PCNA, an indicator of replication or repair, but did not express Ki 67, an indicator of replication. The ultrastructure was not apoptosis or necrosis, but that of living cell with nuclei. That is, TUNEL positive myocytes in hearts with DCM are not apoptotic, but living cells with increasing activity of DNA repair.
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