کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1929136 | 1050446 | 2012 | 6 صفحه PDF | دانلود رایگان |

Overexpression of lipoprotein-associated phospholipase A2 (Lp-PLA2) is implicated in atherosclerosis. We tested the hypothesis that lentivirus-mediated Lp-PLA2 silencing could inhibit atherosclerosis in apolipoprotein E-deficient mice. Sixty eight apolipoprotein E-deficient mice were fed a high-fat diet and a constrictive collar was placed around the left carotid artery to induce plaque formation. The mice were randomly divided into control, negative control (NC) and RNA interference (RNAi) groups. Lp-PLA2 RNAi or scrambled NC lentivirus viral suspensions were constructed and transfected into the carotid plaques 8 weeks after surgery; the control group was administered saline. The carotid plaques were assessed 7 weeks later using hematoxylin and eosin, Masson’s trichrome and oil red O staining; plasma and lesion inflammatory gene expression were examined using ELISAs and real-time PCR. Seven weeks after transfection, the serum concentration and plaque mRNA expression of Lp-PLA2 was significantly lower in the RNAi group, and lead to reduced local and systemic inflammatory gene expression. Lp-PLA2 RNAi also ameliorated plaque progression, reduced the plaque lipid content and increased the plaque collagen content. The effects of Lp-PLA2 RNAi were independent of serum lipoprotein levels, as the triglyceride and total cholesterol levels of the control, NC and RNAi groups were not significantly different. These findings support the hypothesis that lentivirus-mediated Lp-PLA2 gene silencing has therapeutic potential to inhibit atherosclerosis and increase plaque stability, without altering the plasma lipoprotein profile.
Figure optionsDownload as PowerPoint slideHighlights
► Lp-PLA2 RNAi ameliorates atherosclerosis in apolipoprotein E-deficient mice.
► Lp-PLA2 RNAi reduces the expression of inflammatory genes.
► Lp-PLA2 gene silencing represents a new approach for stabilizing vulnerable plaques.
Journal: Biochemical and Biophysical Research Communications - Volume 427, Issue 3, 26 October 2012, Pages 557–562