| First Author | Tsukahara T | Year | 2016 |
| Journal | Biochem Biophys Res Commun | Volume | 473 |
| Issue | 1 | Pages | 107-113 |
| PubMed ID | 27012212 | Mgi Jnum | J:234864 |
| Mgi Id | MGI:5791023 | Doi | 10.1016/j.bbrc.2016.03.060 |
| Citation | Tsukahara T, et al. (2016) Short-term treatment with a 2-carba analog of cyclic phosphatidic acid induces lowering of plasma cholesterol levels in ApoE-deficient mice. Biochem Biophys Res Commun 473(1):107-13 |
| abstractText | Plasma cholesterol levels are associated with an increased risk of developing atherosclerosis. An elevated low-density lipoprotein cholesterol (LDL-C) level is a hallmark of hypercholesterolemia in metabolic syndrome. Our previous study suggested that when acetylated LDL (AC-LDL) was co-applied with a PPARgamma agonist, rosiglitazone (ROSI), many oil red O-positive macrophages could be observed. However, addition of cyclic phosphatidic acid (cPA) to ROSI-stimulated macrophages completely abolished oil red O-stained cells, indicating that cPA inhibits PPARgamma-regulated AC-LDL uptake. This study aimed to determine whether metabolically stabilized cPA, in the form of a carba-derivative of cPA (2ccPA), could reduce plasma cholesterol levels and affect the expression of genes related to atherosclerosis in apolipoprotein E-knockout (apoE(-/-)) mice. 2ccPA reduced LDL-C levels in these mice (n = 3) from 460 to 330 mg/ml, from 420 to 350 mg/ml, and 420 to 281 mg/ml under a western-type diet. 2ccPA also reduced expression of lipid metabolism-related genes, cytokines, and chemokines in ApoE-deficient mice on a high-fat diet. Taken together, these results suggest that 2ccPA governs anti-atherogenic activities in the carotid arteries of apoE-deficient mice. |
