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Treatment of tumor‐induced cardiovascular dysfunction with losartan, an angiotensin II receptor antagonist
Author(s) -
Devine Raymond D,
Stevens Sarah,
Youtz Dane,
Bicer Sabahattin,
Clark Yvonne,
Wold Loren E
Publication year - 2013
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.27.1_supplement.1197.8
Subject(s) - losartan , angiotensin ii , heart failure , ventricle , endocrinology , medicine , autophagy , cachexia , receptor , cancer research , biology , cancer , apoptosis , biochemistry
Tumor burden elicits a multitude of pathological responses from multiple organ systems. Part of this pathological response is cachexia; generalized as host tissue wasting. Angiotensin II(Ang II) has been implicated in the activation of the proteasome. Losartan is a well‐known selective and competitive Ang II receptor antagonist, which is hypothesized to lessen the pathological burden. Raised levels of mRNA of biomarkers for ubiquitin pathway such as MuRF and Bnip3 are present in tumor bearing mice, implicating the role of the ubiqutin pathway. Degradation of myosin heavy chain (MHC) also occurs in the ventricles of the heart. The heart has been observed using echocardiography, which shows a decrease in left ventricle function. Ex vivo cardiomyocyte isolations of tumor burdened mice show deficits in function. Losartan treatment ameliorates the pathology state; it decreases ubiquitin markers coupled with reductions of Bnip3, MuRF, and IL‐6 lessening the effect of cardiac degradation and preserving function. In cardiomyocyte isolations losartan normalized the contractions from tumor bearing mice, this mechanism will need to be explored further. Losartan successfully showed an improvement in cardiac function and normalization of single cardiomyocyte, more experiments are planned in the future to further elucidate the mechanisms of cachexia and the action of losartan on them.