High Density Lipoprotein and Its Precursor Protein Apolipoprotein A1 as Potential Therapeutics to Prevent Anthracycline Associated Cardiotoxicity

Abstract

Cardiovascular disease and cancer are the leading causes of death in developed societies. Despite their effectiveness, many cancer therapies exhibit deleterious cardiovascular side effects such as cardiotoxicity and heart failure. The cardiotoxic effects of anthracyclines such as doxorubicin are the most well-characterized of cardiotoxic anti-cancer therapies. While other anti-neoplastic drugs also induce cardiotoxicity, often leading to heart failure, they are beyond the scope of this review. This review first summarizes the mechanisms of doxorubicin-induced cardiotoxicity. It then reviews emerging preclinical evidence that high density lipoprotein and its precursor protein apolipoprotein A1, which are known for their protective effects against ischemic cardiovascular disease, may also protect against doxorubicin-induced cardiotoxicity both directly and indirectly, when used therapeutically.

A Spontaneous Assembling Lipopeptide Nanoconjugate Transporting the Anthracycline Drug N-Benzyladriamycin-14-valerate for Personalized Therapy of Ewing Sarcoma

“…In support of this concept, the role of SR-B1 in drug delivery is consistent with the flow cytometry findings revealed in this communication, showing the inhibition of ChO* uptake when SR-B1 is blocked (Figure ). Accordingly, the drug payload delivery is achieved without endocytosis of the NP itself, a unique and essential feature of this system, compared to most other nanodelivery approaches. ,− Overexpression of SR-B1 by malignant tumors is an important feature, especially in aggressive cancers. , Our laboratory and several others have reported tumor selective delivery by rHDL nanoparticles via this receptor. − ,− In the present study, we show potentially tumor-selective delivery of the therapeutic payload by the MYR-5A/AD198 NCs, indicating that this formulation is an excellent candidate for personalized therapy for Ewing sarcoma patients and those with other malignancies without affecting off-target (especially cardiac) damage.…”

Role of HDL cholesterol in anthracycline-induced subclinical cardiotoxicity: a prospective observational study in patients with diffuse large B-cell lymphoma treated with R-CHOP

“…Nevertheless, it is crucial to note that HDL-C levels may not accurately reflect the functional properties of HDL. ApoA1, the most abundant protein in HDL, is associated with several beneficial effects of HDL 15 25. The function and abundance of ApoA1 are reported to play a dominant role in HDL quality 26.…”

“…ApoA1, the most abundant protein in HDL, is associated with several beneficial effects of HDL. 15 25 The function and abundance of ApoA1 are reported to play a dominant role in HDL quality. 26 In the context of AIC, several studies have indicated that HDL can protect against anthracycline-induced cardiomyocyte apoptosis and atrophy in isolated cardiomyocytes 27 28 and animal models.…”

“…Its salutary effects include antioxidant, anti-inflammatory and antiapoptotic properties. Numerous preclinical investigations have suggested that HDL may have direct and indirect protective effects against AIC 15–17. The roles of HDL cholesterol (HDL-C) and apolipoprotein A1 (ApoA1) in providing cardiovascular protection of HDL have been the subject of recent debate.…”

Characterization of Cardiac, Vascular, and Metabolic Changes in Young Childhood Cancer Survivors

“…Apo-A1, along with HDL, is well-known for its vasoprotective effects, being involved in the “reverse cholesterol transport” from the periphery to the liver and in arterial plaque inhibition in part via antiinflammatory effects ( 50 ). Apo-A1 is the major protein component of HDL and has been suggested to protect the cardiovascular system against AC toxicity via cytoprotective effects and cardiac “sparing” in delivery of AC ( 51 ). Whether Apo-A1 might be the driving mechanism of the effect observed herein needs to be assessed in future studies.…”