Native and reconstituted HDL protect cardiomyocytes from doxorubicin-induced apoptosis

Abstract

HDL and its sphingosine-1-phosphate component can protect cardiomyocytes against doxorubicin toxicity and may offer one means of reducing cardiotoxic side effects during doxorubicin therapy. The study identified anti-apoptotic pathways that could be exploited to improve cardiomyocyte survival.

Therapeutic Potential of HDL in Cardioprotection and Tissue Repair

“…This protective effect has mainly been evaluated by its capacity to counteract the proapoptotic signals such as caspase 3 activation and DNA fragmentation (Frias et al 2010;Theilmeier et al 2006). HDL incubation induces the phosphorylation of phosphoinositide 3-kinase (PI3K)/Akt, extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen-activated protein kinase (p38 MAPK), and the transcription factor signal transducer and activator of transcription 3 (STAT3) (Frias et al 2009).…”

“…For example, several experiments suggest that S1P3 is involved in PI3K/ Akt signalling and that S1P2 and/or S1P1 might be involved in ERK1/2 and STAT3 signalling (Frias et al 2009;Tao et al 2010). S1P2 was shown to play a key role in the HDL-induced protection against the apoptotic effects of doxorubicin (Frias et al 2010). In the protection against hypoxia reperfusion injury, a predominant, mediatory role was indicated for the S1P1 and S1P3 receptors, via ERK1/2 and PI3K/Akt activation.…”

“…No role was attributed to S1P2, but neither was it investigated (Tao et al 2010). The evidence that reinforces the cytoprotective role of S1P comes from experiments, where addition of S1P to reconstituted HDL (rHDL) containing apo A-I improved the protection against the apoptotic action of doxorubicin (Frias et al 2010). …”

Papel protector de las lipoproteínas de alta densidad en sepsis: aspectos básicos e implicancias clínicas

“…El mecanismo protector de las HDL estaría mediado por la activación de la proteína quinasa Akt, la cual produce señales anti-apoptóticas relacionadas con la inactivación de la vía de la apoptosis mitocondrial 6 . Los componentes de las HDL que activan esta vía de señalización serían la S1P y la apo A-I, que se unen a sus receptores S1P2 y SR-BI, respectivamente 7,8 .…”

The Role of Altered Lipid Metabolism in Septic Myocardial Dysfunction

“…The reduced level of serum HDL and cholesterol in sepsis is explained by a reduced RCT [112] mediated by the LPS-induced downregulation of the scavenger receptors SR-B1 and ABCA1 [113]. The sequestration of the cholesterol into the cell may be useful in the short term, due to the increased delivery to the immune cells, but harmful in the long run because of the decreased delivery to the steroidogenetic and liver cells and to the atherogenic picture it induces.…”