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Caveolin‐3 expression is increased in anthracycline‐induced heart failure in rabbits
Author(s) -
Ichikawa Yasuhiro,
ZemlicHarpf Alice,
Hammond Kirk H,
McKirnan Dan M,
Patel Hemal H,
Roth David M
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.735.1
Subject(s) - heart failure , daunorubicin , ventricle , anthracycline , ejection fraction , medicine , caveolin 3 , cardiology , caveolin , western blot , endocrinology , chemotherapy , signal transduction , chemistry , biology , caveolae , microbiology and biotechnology , cancer , breast cancer , biochemistry , gene
Anthracyclines, such as daunorubicin, are widely used anticancer drugs. Anthracyclines are cardiotoxic and induce development of heart failure during chemotherapy. Caveolins are structural proteins in cell membranes that bind, organize and regulate receptors and signaling molecules. Caveolin‐3, a muscle specific subtype of caveolin, is highly expressed in the heart and is involved in protection of the heart from cardiac stress. In previous reports, left ventricular (LV) caveolin protein expression is decreased in failing hearts after myocardial infarction; however, the effect of anthracycline‐induced heart failure on caveolin expression is not known. We tested the hypothesis that daunorubicin modulates caveolin expression in the heart. Methods New Zealand rabbits were given daunorubicin (3mg/kg, iv) weekly for 8–11 weeks to induce heart failure. LV systolic function was followed using echocardiography and LV fractional shortening (FS) and ejection fraction (EF) were measured. When the LVFS was under 20% (average; 9.0 weeks) heart tissue was collected and divided into 3 parts (LV, intraventricular septum (IVS), right ventricle (RV)). The heart tissue was homogenized and western blot was performed to measure caveolin protein expression. Results Daunorubicin treatment (Dau) resulted in progressive and significant decline of LVFS (Control; 32.4% (n=8) vs Dau; 15.9% (n=6), P<0.001) and EF (Control; 69.1% vs Dau; 38.2%, P<0.001) at the end of study. LV end diastolic dimension in Dau was significantly dilated compared to control group (Control; 16.2 mm vs Dau; 19.2 mm, P<0.05). In control hearts, caveolin‐3 expression in RV was higher than in LV or IVS (2.0 and 1.9 ‐fold vs. LV and IVS, respectively, P<0.01, n=6); however, no significant difference in caveolin‐1 expression was observed in the three regions. In heart failure induced by daunorubicin, caveolin‐3 expression was increased in LV, IVS and RV compared to control tissues (2.8, 2.4 and 2.6‐fold vs. control LV, IVS and RV, P<0.05, n=6, respectively) with no change in caveolin‐1 expression. Conclusions These results suggest that in heart failure induced by daunorubicin caveolin‐3 expression is increased in the rabbit heart. The pathophysiological role for caveolin‐3 in daunorubicin‐induced heart failure remains to be determined.