A novel activator of C-C chemokine, FROUNT, is expressed with C-C chemokine receptor 2 and its ligand in failing human heart.
BACKGROUND
A novel activator of C-C chemokines, FROUNT, directly binds C-C chemokine receptor (CCR) 2 and plays a central role in the chemokine system. Activation of the chemokine system appears to be involved in the pathogenesis of congestive heart failure (CHF). The purpose of this study was to determine whether FROUNT is expressed with CCR2 and its ligand (CCL2) in failing human heart.


RESULTS
We examined endomyocardial biopsy tissues obtained from 71 patients with CHF (HF group) and 20 subjects without CHF (non-HF group). FROUNT, CCR2, and CCL2 mRNA levels were higher in the HF group than in the non-HF group (P < .001). FROUNT mRNA levels were positively correlated with CCR2 and CCL2 mRNA levels in the HF group. FROUNT and CCL2 signal was seen in the cytoplasm of cardiac myocytes in failing hearts. Levels of FROUNT mRNA were negatively correlated with left ventricular ejection fraction. FROUNT, CCR2, and CCL2 mRNA levels were higher in the severe HF subgroup than in the mild HF subgroup.


CONCLUSIONS
The expression of FOUNT-mediated CCL2/CCR2 may have important implications in the pathogenesis of CHF. The CCL2/CCR2 pathway via FROUNT may influence the clinical severity of CHF.
Satoh
Mamoru
M
Second Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan.
Akatsu
Tomonari
T
Ishkawa
Yuh
Y
Minami
Yoshitaka
Y
Nakamura
Motoyuki
M
D015415:Biomarkers / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics*; D033922:Clathrin Heavy Chains / Q000096:biosynthesis / Q000235:genetics*; D015342:DNA Probes; D018450:Disease Progression; D004699:Endocardium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D008024:Ligands; D008297:Male; D008875:Middle Aged; D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
D015415:Biomarkers; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D015342:DNA Probes; D008024:Ligands; C503214:NUP85 protein, human; D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D033922:Clathrin Heavy Chains