P494Ox-HDL Modulates the expression of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) expression and proinflammatory cytokines in human differentiated monocytes in atherosclerosis.

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Introduction: Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is the main scavanger receptor for oxidized low density lipoprotein (OxLDL) and highly expressed in endothelial cells of atherosclerotic lesions, Its expression has also been found to be unregulated by the several inflammatory cytokines (such as TNF-α, IL-8) under oxidative stress and various pathological conditions, such as hyperlowdensity lipoproteinemia, dyslipidemia, hypertension, and diabetes.Methods: Isolated fractions of HDL were modified and expression profiling of LOX-1 and associated different inflammatory genes were studied both at mRNA and protein levels in PMA differentiated monocytes in presence and absence of both nHDL and Ox-HDL. The expression of NF-kappa B protein was studied by electrophoretic mobility shift assay under same conditions, futher the expression of cIAPs proteins was also studied in differentiated monocyte to develop the cross talk if any between expression of LOX-1 and inflammation during progression of atherosclerosisResults and conclusion: High density lipoprotein (HDL) possess anti-oxidative and anti-inflammatory characteristics , however under stressed pathological conditions HDL undergoes modification and become associated with inflammation and oxidative stress, HDL become dysfunctional and exhibit pro-inflammatory properties. In vitro, HDL can be modified by oxidation of lipid and protein moiety under the atherosclerotic conditions. Here we reported that, after modification due to oxidation , HDL lose their ability to inhibit the expression of LOX-1 expression which is induced by pro-inflammatory cytokines under pathological conditions in differentiated monocytes in addition, oxidatively modified HDL induce the higher expression of LOX-1 both at mRNA and protein levels. These studies were further confirmed by studying the expression of NF-kappa B transcription factor which modulates the function of various pro inflammatory genes including TNF-α and IL-8. Altogether these findings confirmed that oxidatively modified HDL possess a pro-atherogenic role and leads to the progression of atherosclerosis.

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