Myocardial expression of fas and recovery of left ventricular function in patients with recent-onset cardiomyopathy.

Abstract

OBJECTIVES:

This study aimed to evaluate the role of gene expression for predicting myocardial recovery in recent-onset cardiomyopathy.

BACKGROUND:

Apoptosis may limit ventricular recovery. We examined the myocardial expression of Fas, Fas ligand (FasL), tumor necrosis factor (TNF)-alpha, and TNF receptor 1 (TNFR1), and myocardial recovery in patients from the multicenter Intervention in Myocarditis and Acute Cardiomyopathy (IMAC) study.

METHODS:

Endomyocardial biopsy samples were obtained in 20 patients with recent-onset (<6 months) idiopathic dilated cardiomyopathy (left ventricular ejection fraction [LVEF] < or =0.40). The LVEF was assessed at baseline and at 6 and 12 months by nuclear scans. Myocardial expression was assessed by ribonuclease (RNase) protection, normalized to a constitutively active gene (glyceraldehydes 3-phosphate dehydrogenase [GAPDH]) and reported as percent GAPDH expression. The change in LVEF at 6 and 12 months was compared by tertiles of expression.

RESULTS:

For all patients (14 men, 6 women; age 46.5 +/- 10.7 years), the mean LVEF was 0.28 +/- 0.05 at baseline and 0.40 +/- 0.14 at six months. Patients in the highest tertile of Fas expression had minimal improvement at six months (DeltaEF = 0.03 +/- 0.05) when compared with the intermediate (DeltaEF = 0.10 +/- 0.13) and lowest tertiles (DeltaEF = 0.21 +/- 0.11, change in LVEF by tertile, p = 0.006). A similar relationship was seen with TNFR1 expression (highest tertile, DeltaEF = 0.06 +/- 0.07; lowest tertile, DeltaEF = 0.21 +/- 0.11, p = 0.02). In contrast with Fas and TNFR1, expression of TNF-alpha and FasL did not predict recovery of LV function.

CONCLUSIONS:

In cardiomyopathy of recent onset, increased expression of Fas and TNFR1 was associated with minimal recovery of LV function. Apoptosis limits myocardial recovery, and represents a potential target for therapeutic intervention.

• Authors: Richard Sheppard, Maninder Bedi, Toru Kubota, Marc J Semigran, William Dec, Richard Holubkov, Arthur M Feldman, Warren D Rosenblum, Charles F McTiernan, Dennis M McNamara, IMAC Investigators
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 46 Issue 6 Pg. 1036-42 (Sep 20 2005) ISSN: 1558-3597 [Electronic] United States
• PMID: 16168288 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• FASLG protein, human
• Fas Ligand Protein
• Membrane Glycoproteins
• Receptors, Tumor Necrosis Factor, Type I
• Tumor Necrosis Factor-alpha
• Tumor Necrosis Factors
• fas Receptor

Topics

• Adult
• Cardiomyopathies (drug therapy, metabolism, physiopathology)
• Fas Ligand Protein
• Female
• Humans
• Male
• Membrane Glycoproteins (biosynthesis)
• Middle Aged
• Receptors, Tumor Necrosis Factor, Type I (biosynthesis)
• Recovery of Function
• Time Factors
• Tumor Necrosis Factor-alpha (biosynthesis)
• Tumor Necrosis Factors (biosynthesis)
• Ventricular Function, Left
• fas Receptor (biosynthesis)