title: Induction of brain natriuretic peptide and monocyte chemotactic protein-1 gene expression by oxidized low-density lipoprotein: relevance to ischemic heart failure.
abstract: Brain natriuretic peptide (BNP) and monocyte chemotactic protein-1 (MCP-1) are biomarkers of heart failure (HF). The aim of the present study was to determine the role of oxidized low-density lipoprotein (Ox-LDL) in the induction of these biomarkers and the signaling pathways involved in vitro. Incubation of HL-1 cardiomyocytes and human myocytes with Ox-LDL induced the expression of BNP and MCP-1 genes, while native LDL had no effect. When peroxides associated with Ox-LDL were reduced to hydroxides, the ability to induce BNP and MCP-1 gene expression was abolished. Furthermore, exposure of HL-1 cells to ischemic conditions alone had no effect on BNP gene expression, while ischemia followed by reperfusion resulted in increased expression of BNP gene. Inhibitors of ERK and JNK inhibited the induction of BNP. Signaling array results suggested that the induction of both MAPK and NF-κB pathways is involved in the induction of BNP by Ox-LDL. These results suggest that Ox-LDL or peroxidized lipids formed in oxidatively stressed myocytes during ischemia-reperfusion injury may play a role in the induction of BNP and MCP-1.
authors: Division of Cardiac Surgery, The Ohio State University Medical Center, Columbus, Ohio 43210-1292, USA.
authors: Aluganti N
authors: AN
authors: Chandrakala
authors: Devraj
authors: D
authors: Sukul
authors: Krithika
authors: K
authors: Selvarajan
authors: Chittoor
authors: C
authors: Sai-Sudhakar
authors: Benjamin
authors: B
authors: Sun
authors: Sampath
authors: S
authors: Parthasarathy
mesh_terms: D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000502:physiology*; D017202:Myocardial Ischemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis / Q000235:genetics*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics
chemical_list: D018932:Chemokine CCL2; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D020097:Natriuretic Peptide, Brain