Microparticles and cardiotoxicity secondary to doxorubicin-based chemotherapy in breast cancer patients

Breast cancer is the most common cancer in women and the fifth leading cause of cancer mortality worldwide [1]. Doxorubicin (DOXO) is an anthracycline and one of the main drugs used in breast cancer chemotherapy. However, its use is limited due to the cumulative and dose-dependent cardiotoxicity. Cardiotoxicity secondary to anthracycline starts with myocardial cell damage, followed by left ventricular dysfunction. Anthracycline induces excessive production of free radicals and iron ions in cardiomyocytes, such as induction of apoptosis, and lipid bilayer damage [[2], [3], [4]]. Since cardiovascular and oncology diseases are the most common death causes in worldwide, a new subspecialty emerges - the cardio-oncology [5].

Microparticles (MPs) are extracellular vesicles (EVs) derived from plasma membrane, delimited by a lipid bilayer and cannot replicates. Cells can generates and releases MPs by several physiological and pathophysiological mechanisms or stimuli, during cellular differentiation or senescence, exposure to high shear stress, apoptosis or upon pro-inflammatory or pro-thrombotic stimulations. The release of MPs from the cells is observed with an increase in intracellular calcium, thus changing the positions of phospholipids, inverting phosphatidylserine (PS) from the inside to the outside of the membrane [6,7]. MPs are stable in extracellular environment and are found in abundance in peripheral blood. In addition, they carry proteins, lipids, nucleic acids, and other molecules that reflect their tissues of origin. These characteristics enable MPs to be studied as disease biomarkers [8].

Recent studies have shown that tumor-derived EVs carry signaling molecules capable of interacting with circulating cells (especially immune cells), in favor to pro-inflammatory tumor microenvironment, and have a linkage with coagulation process [9,10]. The potential role of EVs in diagnostic, prognostic and therapeutic of breast cancer has been increasingly studied. Recently, we showed that hemostatic changes is also associated with cardiotoxicity in breast cancer women under DOXO treatment [11]. In this context, the aim of this study was to evaluate total-MPs and MPs derived from platelets, cardiomyocytes and those that express tissue factor (TF) and their relationship with DOXO-cardiotoxicity in breast cancer women.

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