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Doxorubicin, an agent used to treat a variety of cancers, is cardiotoxic by triggering cardiomyocyte apoptosis. We previously showed that treating cultured cardiomyocytes with human high density lipoprotein in vitro or transgenic overexpression of human apolipoprotein A1, its main structural protein protects against doxorubicin induced cardiomyocyte apoptosis in a manner dependent on the scavenger receptor class B type I [Durham (2018) 314: H31-H44]. This was due to high density lipoprotein induced activation of Akt signaling in cardiomyocytes. We now demonstrate that mice lacking the scavenger receptor class B type I exhibit increased sensitivity to doxorubicin-induced cardiomyocyte apoptosis in vivo. Cardiomyocytes expressing scavenger receptor class B type I are protected from doxorubicin-induced apoptosis by pre-incubation with high density lipoprotein isolated from wild type mice, whereas high density lipoprotein from scavenger receptor class B type 1 knockout mice is less effective. Cardiomyocytes from scavenger receptor class B type I knockout mice, however, are not protected by high density lipoprotein in vitro and hearts from knockout mice are more sensitive to doxorubicin in vivo. Pharmacological administration of purified apolipoprotein A1 dramatically protected wild type mice from doxorubicin-induced cardiotoxicity and left ventricular dysfunction, whereas this protection was lost in scavenger receptor class B type I-deficient mice. This demonstrates, at least in mice, that high density lipoprotein therapy can confer protection against doxorubicin-induced cardiomyocyte apoptosis in a manner mediated by the scavenger receptor class B type I.
This article was published in the following journal.
Name: American journal of physiology. Heart and circulatory physiology
To evaluate the cardio-protective effect of Ginkgo Biloba (GB) on doxorubicin induced-cardiotoxicity.
Doxorubicin, an antibiotic belonging to anthracycline family, has been used for treatment of malignancies. Cardiotoxicity is the main adverse effect of doxorubicin. Apigenin, as a flavonoid, has antio...
Improvements in cancer treatment have significantly extended the lifespan of patients. However, due to the adverse effects of cancer treatment, cancer survivors are at increased risk of cardiovascular...
The clinical use of the chemotherapeutic doxorubicin (Dox) is limited by cardiotoxic side-effects. One of the early Dox effects is induction of a sarcoplasmic reticulum (SR) Ca2+ leak. The chaperone G...
Doxorubicin (DOX), is a chemotherapeutic agent, which evokes oxidative stress and cell apoptosis in testicular tissue. It is known that the activation of the nuclear enzyme poly (ADP-ribose) polymeras...
Analyze pharmacokinetics of doxorubicin in children with cancer. Furthermore investigate the predictive role of troponin and natriuretic peptides for anthracycline-induced cardiotoxicity .
The purpose of this research study is to determine whether early administration of Dexrazoxane prevents Doxorubicin induced cardiotoxicity.
To determine the role of apolipoprotein B and apolipoprotein A1 in the etiology of coronary artery disease.
The purpose of this study is to support the qualification of a replacement manufacturing site for DOXIL/CAELYX (doxorubicin HCL).
The purpose of this research study is to look at whether giving a drug called dexrazoxane with standard of care doxorubicin affects the progression of the disease. Dexrazoxane is often giv...
Species of GAMMARETROVIRUS, containing many well-defined strains, producing leukemia in mice. Disease is commonly induced by injecting filtrates of propagable tumors into newborn mice.
A major and the second most common isoform of apolipoprotein E. In humans, Apo E4 differs from APOLIPOPROTEIN E3 at only one residue 112 (cysteine is replaced by arginine), and exhibits a lower resistance to denaturation and greater propensity to form folded intermediates. Apo E4 is a risk factor for ALZHEIMER DISEASE and CARDIOVASCULAR DISEASES.
A 34-kDa glycosylated protein. A major and most common isoform of apolipoprotein E. Therefore, it is also known as apolipoprotein E (ApoE). In human, Apo E3 is a 299-amino acid protein with a cysteine at the 112 and an arginine at the 158 position. It is involved with the transport of TRIGLYCERIDES; PHOSPHOLIPIDS; CHOLESTEROL; and CHOLESTERYL ESTERS in and out of the cells.
The second most abundant protein component of HIGH DENSITY LIPOPROTEINS or HDL. It has a high lipid affinity and is known to displace APOLIPOPROTEIN A-I from HDL particles and generates a stable HDL complex. ApoA-II can modulate the activation of LECITHIN CHOLESTEROL ACYLTRANSFERASE in the presence of APOLIPOPROTEIN A-I, thus affecting HDL metabolism.
One of three major isoforms of apolipoprotein E. In humans, Apo E2 differs from APOLIPOPROTEIN E3 at one residue 158 where arginine is replaced by cysteine (R158--C). In contrast to Apo E3, Apo E2 displays extremely low binding affinity for LDL receptors (RECEPTORS, LDL) which mediate the internalization and catabolism of lipoprotein particles in liver cells. ApoE2 allelic homozygosity is associated with HYPERLIPOPROTEINEMIA TYPE III.
Recombinant DNA is the formation of a novel DNA sequence by the formation of two DNA strands. These are taken from two different organisms. These recombinant DNA molecules can be made with recombinant DNA technology. The procedure is to cut the DNA of ...