title: Eicosapentaenoic acid suppresses adverse effects of C-reactive protein overexpression on pressure overload-induced cardiac remodeling.
abstract: Serum C-reactive protein (CRP) elevation is associated with poor clinical outcome in patients with heart failure (HF). We previously reported that CRP exacerbates the development of pressure overload-induced cardiac remodeling through an enhanced inflammatory response and oxidative stress. In the present study, we examined the effect of eicosapentaenoic acid (EPA), a suppressor of inflammatory response and oxidative stress, on pressure overload-induced cardiac remodeling. Transverse aortic constriction (TAC) was performed on transgenic mice overexpressing CRP (CRPtg) and nontransgenic littermates (TAC/CON). CRPtg with TAC operation were randomly assigned to be fed a standard diet (TAC/CRPtg) or an EPA-enriched diet (7 % of total energy) (TAC/CRPtg/EPA). Myocardial mRNA level of transforming growth factor-β1, proinflammatory cytokines, and oxidative stress markers were increased in TAC/CRPtg in comparison with TAC/CON 1 and 4 weeks after the operation. These parameters were significantly suppressed in TAC/CRPtg/EPA compared with TAC/CRPtg. In addition, after 4 weeks of EPA treatment, as compared with TAC/CRPtg, TAC/CRPtg/EPA mice demonstrated reduced heart and lung weights, increased left ventricular fractional shortening, and decreased left ventricular end-diastolic pressure, together with decreased cardiac hypertrophy, fibrosis, and improved cardiac function. In conclusion, the anti-inflammatory and antioxidative properties of EPA may make it an effective therapeutic strategy for adverse cardiac remodeling associated with CRP overexpression.
authors.affiliation: Division of Cardiology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nagai
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Anzai
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Mano
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Kaneko
authors.forename: Atsushi
authors.initials: A
authors.lastname: Anzai
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugano
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Maekawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005355:Fibrosis; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D020127:Recovery of Function; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D002097:C-Reactive Protein; D015118:Eicosapentaenoic Acid