title: Interleukin-16 promotes cardiac fibrosis and myocardial stiffening in heart failure with preserved ejection fraction.
abstract: BACKGROUND
  Chronic heart failure (CHF) with preserved left ventricular (LV) ejection fraction (HFpEF) is observed in half of all patients with CHF and carries the same poor prognosis as CHF with reduced LV ejection fraction (HFrEF). In contrast to HFrEF, there is no established therapy for HFpEF. Chronic inflammation contributes to cardiac fibrosis, a crucial factor in HFpEF; however, inflammatory mechanisms and mediators involved in the development of HFpEF remain unclear. Therefore, we sought to identify novel inflammatory mediators involved in this process.
  
  
  RESULTS
  An analysis by multiplex-bead array assay revealed that serum interleukin-16 (IL-16) levels were specifically elevated in patients with HFpEF compared with HFrEF and controls. This was confirmed by enzyme-linked immunosorbent assay in HFpEF patients and controls, and serum IL-16 levels showed a significant association with indices of LV diastolic dysfunction. Serum IL-16 levels were also elevated in a rat model of HFpEF and positively correlated with LV end-diastolic pressure, lung weight and LV myocardial stiffness constant. The cardiac expression of IL-16 was upregulated in the HFpEF rat model. Enhanced cardiac expression of IL-16 in transgenic mice induced cardiac fibrosis and LV myocardial stiffening accompanied by increased macrophage infiltration. Treatment with anti-IL-16 neutralizing antibody ameliorated cardiac fibrosis in the mouse model of angiotensin II-induced hypertension.
  
  
  CONCLUSIONS
  Our data indicate that IL-16 is a mediator of LV myocardial fibrosis and stiffening in HFpEF, and that the blockade of IL-16 could be a possible therapeutic option for HFpEF.
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tamaki
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Mano
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sakata
authors.forename: Tomohito
authors.initials: T
authors.lastname: Ohtani
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Takeda
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kamimura
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Omori
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Tsukamoto
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Ikeya
authors.forename: Mari
authors.initials: M
authors.lastname: Kawai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hagihara
authors.forename: Ryohei
authors.initials: R
authors.lastname: Ishii
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Higashimori
authors.forename: Makoto
authors.initials: M
authors.lastname: Kaneko
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hasuwa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miwa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000150:complications; D019410:Interleukin-16 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D012307:Risk Factors; D013318:Stroke Volume / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D019410:Interleukin-16
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