RGD Reference Report - Electronegative low-density lipoprotein induces cardiomyocyte apoptosis indirectly through endothelial cell-released chemokines. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Electronegative low-density lipoprotein induces cardiomyocyte apoptosis indirectly through endothelial cell-released chemokines.

Authors: Lee, AS  Wang, GJ  Chan, HC  Chen, FY  Chang, CM  Yang, CY  Lee, YT  Chang, KC  Chen, CH 
Citation: Lee AS, etal., Apoptosis. 2012 Sep;17(9):1009-18. doi: 10.1007/s10495-012-0726-1.
RGD ID: 7257691
Pubmed: PMID:22562555   (View Abstract at PubMed)
DOI: DOI:10.1007/s10495-012-0726-1   (Journal Full-text)

Cardiomyocyte apoptosis has a critical role in the pathogenesis of heart failure. L5, the most negatively charged subfraction of human plasma low-density lipoprotein (LDL), induces several atherogenic responses in endothelial cells (ECs), including apoptosis. We hypothesized that L5 also contributes to cardiomyocyte apoptosis and studied whether it does so indirectly by inducing the secretion of factors from ECs. We examined apoptosis of rat cardiomyocytes treated with culture-conditioned medium (CCM) of rat ECs that were exposed to L5 or L1 (the least negatively charged LDL subfraction). Apoptosis at early and late time points was twofold greater in cardiomyocytes treated with L5 CCM than in those treated with L1 CCM. The indirect effect of L5 on cardiomyocyte apoptosis was significantly reduced by pretreating ECs with inhibitors of phosphatidylinositol 3-kinase (PI3K) or CXC receptor 2 (CXCR2). Studies with cytokine protein arrays revealed that L5 CCM, but not L1 CCM, contained high levels of ELR(+) CXC chemokines, including lipopolysaccharide-induced chemokine (LIX) and interleukin (IL)-8. The L5-induced release of these chemokines from ECs was abolished by inhibiting the lectin-like oxidized LDL receptor-1 (LOX-1). Addition of recombinant LIX or IL-8 to CCM-free cardiomyocyte cultures increased apoptosis and enhanced production of tumor necrosis factor (TNF)-alpha and IL-1beta by increasing the translocation of NF-kappaB into the nucleus; these effects were attenuated by inhibiting PI3K and CXCR2. In conclusion, L5 may indirectly induce cardiomyocyte apoptosis by enhancing secretion of ELR(+) CXC chemokines from ECs, which in turn activate CXCR2/PI3K/NF-kappaB signaling to increase the release of TNF-alpha and IL-1beta.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cardiac muscle cell apoptotic process  IMP 7257691 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cxcr2  (C-X-C motif chemokine receptor 2)


Additional Information