Early biomarkers of doxorubicin-induced heart injury in a mouse model

Desai, Varsha G.; Kwekel, Joshua C.; Vijay, Vikrant; Moland, Carrie L.; Herman, Eugene H.; Lee, Taewon; Han, Tao; Lewis, Sherry M.; Davis, Kelly J.; Muskhelishvili, Levan; Kerr, Susan L.; Fuscoe, James C.

doi:10.1016/j.taap.2014.10.006

Cited by 86 publications

(92 citation statements)

References 56 publications

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“…Conversely, the choice of miR-423-5p, previously associated to heart failure [23], is less clear, since anthracycline-triggered cardiac dysfunction is usually observed late after treatment [24]. An additional good candidate for evaluation could be represented by miR-34, which was indicated as regulated by Dox from several groups, even in the plasma of rats [20,25,26]. Given the high novelty and potential clinical relevance of this kind of study, probably a screening of expression of circulating…”

Section: Circulating Mirnasmentioning

confidence: 99%

Early diagnosis of doxorubicin-induced cardiotoxicity:The miRNA way

D’Alessandra¹

2017

Cardiovasc Disord Med

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This short commentary focuses on the use of circulating microRNAs as biomarkers of doxorubicin-induced cardiotoxicity in cancer patients undergoing chemotherapy. Cancer is one of the leading causes of death worldwide and is usually treated following different approaches; among these, anticancer drugs have a very important role. One of the most effective molecules is Doxorubicin (DOX), a two-edged sword which combines several beneficial effects with the lack of cancer-cell specificity. DOX toxicity is known to be able to compromise the clinical effectiveness of chemotherapy, strongly impacting patients' quality of life and survival, even years after its administration. It is associated with progressive disruption of cardiac function, and can progressively develop into heart failure. Despite the availability of different cardiac biomarkers (i.e., troponins, B-type natriuretic peptide) presenting several positive features like high sensitivity, cardiac specificity and low invasivity, reliable and timely risk assessment in long-term cancer survivors is still difficult to achieve. Indeed, cardiotoxicity is usually detected late when heart impairment has already occurred and is quite evident. Evaluation of left ventricle ejection fraction (LVEF) by imaging techniques is still the only reliable and accepted diagnostic tool but does not allow early prevention. In the past years, several efforts were made to identify new biomarkers for early assessment and diagnosis of cardiovascular diseases. Lately, a new class of circulating molecules, microRNAs (miRNAs), emerged, and many groups evidenced their possible exploitation as biomarkers due to their stability in several body fluids and to the possibility to detect them even at small concentrations. Despite the clinical relevancy, only a handful of studies have focused their attention on investigating the role of microRNAs in DOX-induced cardiotoxicity, mostly relying on the use animal models. Very recently, a few groups started to examine whether circulating miRNAs could represent new and reliable early cardiotoxicity biomarkers.

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Section: Circulating Mirnasmentioning

confidence: 99%

Early diagnosis of doxorubicin-induced cardiotoxicity:The miRNA way

D’Alessandra¹

2017

Cardiovasc Disord Med

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“…Calvano, et al [47] reported that miRNA-133a/b are sensitive and specific markers of skeletal muscle and cardiac toxicity and that miRNA-208 used in combination with miRNA-133a/b can be used to differentiate cardiac from skeletal muscle toxicity. Desai et al [49] using a chronic doxorubicin cardiotoxicity mouse model found that pro-apoptotic miRNA-34a showed a significant dose-related up-regulated and was associated with down-regulation of hypertrophy-related miRNA-150. Authors suggested that these findings may lead to the development of biomarkers of earlier events in doxorubicin-induced cardiotoxicity that occur before the release of cardiac troponins [49].…”

Section: Micrornasmentioning

confidence: 99%

“…Desai et al [49] using a chronic doxorubicin cardiotoxicity mouse model found that pro-apoptotic miRNA-34a showed a significant dose-related up-regulated and was associated with down-regulation of hypertrophy-related miRNA-150. Authors suggested that these findings may lead to the development of biomarkers of earlier events in doxorubicin-induced cardiotoxicity that occur before the release of cardiac troponins [49]. By now, the development of miRNAs as clinical biomarkers has been hindered by the lack of standardization [50].…”

Section: Micrornasmentioning

confidence: 99%

Determination of early tumoricidal drug-induced cardiotoxicity with biological markers

Berezin¹

2016

J Transl Sci

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Cardiotoxicity due to tumoricidal drug use is defined as an asymptomatic reduction in left ventricular (LV) ejection fraction (EF) of ≥ 10% to <55% or as a reduction of the LVEF of ≥ 5% to <55% with symptoms of heart failure (HF). The implementation in routine practices the highly tumoricidal anthracycline drugs, taxanes, and trastuzumab cause progressive LV dysfunction and symptomatic HF in dose-dependent manner. Despite there is potent reversibility of tumoricidal drug-induced cardiotoxicity, this adverse effect frequently consists continuously and might lead to limited response to medical treatment and worse survival sufficiently. The aim of the mini review is consideration the clinical evidence that supports the use of cardiac biomarkers for early detection of cardiotoxicity. The review is reported that the identification of cancer patient with increased risk of early cardiotoxicity would allow not only prevention and diagnosis of chemotherapy related cardiotoxicity but also administration of optimal dose and duration of chemotherapy. The predictive role of brain natriuretic peptides, cardiac troponins, microRNAs, S100A1 and inflammatory biomarkers (C-reactive protein) is discussed.

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“…Downregulation of miR-30b has also been documented in H9C2 rat cardiomyocytes following hypoxia/re-oxygenation (24). Interestingly, other groups that generated cardiac miRNA profiles in animal models exposed to DOX had unique signatures that did not uncover miR-30 family members as being significantly dis-regulated (25,26). Nonetheless, there is quite a bit of variability in the timing of DOX exposure, the genetic background, and the technology used to generate these profiles.…”

Section: Introduction To the Biology Of Anthracycline Toxicity In Thementioning

confidence: 99%

Sarco“MiR” friend or foe: a perspective on the mechanisms of doxorubicin-induced cardiomyopathy

Saddic

Muehlschlegel

2016

Annals of Translational Medicine

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Anthracyclines are a class of chemotherapeutics used to treat a variety of human cancers including both solid tumors such as breast, ovarian, and lung, as well as malignancies of the blood including leukemia and lymphoma. Despite being extremely effective anti-cancer agents, the application of these drugs is offset by side effects, most notably cardiotoxicity. Many patients treated with doxorubicin (DOX), one of the most common anthracyclines used in oncology, will develop radiographic signs and/or symptoms of cardiomyopathy. Since more and more patients treated with these drugs are surviving their malignancies and manifesting with heart disease, there is particular interest in understanding the mechanisms of anthracycline-induced injury and developing ways to prevent and treat its most feared complication, heart failure. MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of mRNAs. Since miRNAs can regulate many mRNAs in a single network they tend to play a crucial role in the pathogenesis of several diseases, including heart failure. Here we present a perspective on a recent work by Roca-Alonso and colleagues who demonstrate a cardioprotective function of the miR-30 family members following DOX-induced cardiac injury. They provide evidence for direct targeting of these miRNAs on key elements of the β-adrenergic pathway and further show that this interaction regulates cardiac function and apoptosis. These experiments deliver fresh insights into the biology of toxin-induced cardiomyopathy and suggest the potential for novel therapeutic targets.

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Early biomarkers of doxorubicin-induced heart injury in a mouse model

Cited by 86 publications

References 56 publications

Early diagnosis of doxorubicin-induced cardiotoxicity:The miRNA way

Early diagnosis of doxorubicin-induced cardiotoxicity:The miRNA way

Determination of early tumoricidal drug-induced cardiotoxicity with biological markers

Sarco“MiR” friend or foe: a perspective on the mechanisms of doxorubicin-induced cardiomyopathy

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