Evidence for a role of mast cells in the evolution to congestive heart failure.
Mast cells are believed to be involved in the pathophysiology of heart failure, but their precise role in the process is unknown. This study examined the role of mast cells in the progression of heart failure, using mast cell-deficient (WBB6F1-W/W(v)) mice and their congenic controls (wild-type [WT] mice). Systolic pressure overload was produced by banding of the abdominal aorta, and cardiac function was monitored over 15 wk. At 4 wk after aortic constriction, cardiac hypertrophy with preserved left ventricular performance (compensated hypertrophy) was observed in both W/W(v) and WT mice. Thereafter, left ventricular performance gradually decreased in WT mice, and pulmonary congestion became apparent at 15 wk (decompensated hypertrophy). In contrast, decompensation of cardiac function did not occur in W/W(v) mice; left ventricular performance was preserved throughout, and pulmonary congestion was not observed. Perivascular fibrosis and upregulation of mast cell chymase were all less apparent in W/W(v) mice. Treatment with tranilast, a mast cell-stabilizing agent, also prevented the evolution from compensated hypertrophy to heart failure. These observations suggest that mast cells play a critical role in the progression of heart failure. Stabilization of mast cells may represent a new approach in the management of heart failure.
Hara
Masatake
M
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8397, Japan.
Ono
Koh
K
Hwang
Myung-Woo
MW
Iwasaki
Atsushi
A
Okada
Masaharu
M
Nakatani
Kazuki
K
Sasayama
Shigetake
S
Matsumori
Akira
A
D000818:Animals; D020296:Animals, Congenic; D009320:Atrial Natriuretic Factor / Q000235:genetics; D053818:Chymases; D004195:Disease Models, Animal; D015870:Gene Expression; D006333:Heart Failure / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012697:Serine Endopeptidases / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000517:prevention & control; D016277:Ventricular Function, Left; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D062367:ortho-Aminobenzoates; D009320:Atrial Natriuretic Factor; D012697:Serine Endopeptidases; D053818:Chymases; C012293:tranilast