Plasma level Hsp27 as a Potential Biomarker of Doxorubicin‐induced Heart Failure

Doxorubicin (Dox) is known to cause oxidative stress‐induced heart failure among the cancer patients who were treated with this drug. An early detection of a reliable biomarker of cardiotoxicity will be useful to modify the future regimens of this drug for the patients who are under potential risk of heart failure. We have found that plasma level Hsp25 increases upon treating with Dox in animal models by the time the cardiac dysfunction starts. Mice were treated with Dox (6mg/kg ) for 4 weeks and blood samples were collected once in a week for 4 weeks of post drug treatment. Plasma level Hsp25 remained almost the same for the first three weeks, but from fourth week onwards it increased more than eight fold (8.75±.68, p = < 0.001, n = 12). From fourth week onwards echo showed symptoms of cardiac failure (%FS reduced from 46.7±3.6 (n=12) to 26.8±1.2 (n=12, p < 0.001). We propose that the HSF‐1 responds to Dox induced oxidative stress and increased Hsp25. To confirm this, we found the HSF‐1 knock out mice (HSF‐1 −/− ) were resistant to Dox induced heart failure. For HSF‐1 −/− mice, the 50% survival was found to be beyond 33 ± 2 days (Log‐Rank test). In this case, 40% of the animals survived until the study was completed (100 days), unlike the wild type where the 50% survival was only 23±3 days, and almost all the animals died by end of the study. Thus increased level in Hsp25 may serve as a potential marker of heart failure among Dox treated cancer patients.