Analysis of circulating apoptosis mediators and proinflammatory cytokines in patients with idiopathic hypertrophic cardiomyopathy: comparison between nonobstructive and dilated-phase hypertrophic cardiomyopathy.
We examined the plasma levels of soluble Fas (sFas) or Fas ligand (sFas-L), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in patients with idiopathic nonobstructive (HNCM) and dilated-phase (DHCM) hypertrophic cardiomyopathy. Patients with idiopathic hypertrophic cardiomyopathy (HCM) may deteriorate to DHCM and the pathogenesis is unknown. The levels of these plasma cytokines were measured by ELISA and echocardiography was performed in 38 HNCM and 11 DHCM patients, and 10 normal subjects. The follow-up period was three years. In HNCM, TNF-alpha (43.3 +/- 45.2 versus 16.9 +/- 4.3 pg/mL) and IL-6 (65.1 +/- 86.4 versus 4.0 +/- 2.1 pg/mL) were slightly higher compared to normal subjects and sFas (3.7 +/- 1.2 versus 2.1 +/- 0.7 ng/mL) increased significantly. sFas (3.9 +/- 1.8), TNF-alpha (79.3 +/- 72.4), and IL-6 (234.1 +/- 135.2) in DHCM were significantly increased and only IL-6 was significantly different from HNCM. sFas-L (0.18 +/- 0.08 versus 0.25 +/- 0.05 ng/mL) in HNCM was significantly decreased, and the decrease was marked in DHCM (0.05 +/- 0.02). In HNCM, TNF-alpha was negatively correlated with fractional shortening (r = -0.432, P = 0.0062) or positively with IL-6 (r = 0.665, P < 0.0001), while sFas-L was negatively correlated with IL-6 (r = -0.580, P < 0.0001). DHCM with high sFas had significantly higher cumulative incidences of worsening heart failure. The Fas/Fas-L system and proinflammatory cytokines may play an important role in the status of HCM and its progression to DHCM.
Zen
Kan
K
Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Agaru, Kyoto, Japan.
Irie
Hidekazu
H
Doue
Tomoki
T
Takamiya
Michitaka
M
Yamano
Tetsuhiro
T
Sawada
Takahisa
T
Azuma
Akihiro
A
Matsubara
Hiroaki
H
D000368:Aged; D017209:Apoptosis; D009320:Atrial Natriuretic Factor / Q000097:blood; D002311:Cardiomyopathy, Dilated / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D016207:Cytokines / Q000097:blood* / Q000502:physiology; D018450:Disease Progression; D004452:Echocardiography; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019014:fas Receptor / Q000097:blood
D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor