| First Author | Reddy ST | Year | 2004 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 24 |
| Issue | 9 | Pages | 1676-81 |
| PubMed ID | 15242861 | Mgi Jnum | J:102220 |
| Mgi Id | MGI:3607069 | Doi | 10.1161/01.ATV.0000138342.94314.64 |
| Citation | Reddy ST, et al. (2004) Potential role for mitogen-activated protein kinase phosphatase-1 in the development of atherosclerotic lesions in mouse models. Arterioscler Thromb Vasc Biol 24(9):1676-81 |
| abstractText | OBJECTIVE: Mitogen-activated protein kinase phosphatase-1 (MKP-1) is one of several oxidized-l-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (Ox-PAPC)-induced genes identified in human aortic endothelial cells (HAEC). We previously reported that MKP-1 activity is required for Ox-PAPC-mediated endothelial/monocyte interactions; however, an in vivo role of MKP-1 in atherogenesis has not been investigated. METHODS AND RESULTS: We now report that MKP-1 protein is expressed in the atherosclerotic lesions of mice. MKP-1 mRNA expression is highly induced in C57BL6/J mice on an atherogenic diet, low-density lipoprotein receptor (LDLR) (-/-) mice on a Western diet, and 10-week or older ApoE (-/-) mice on a chow diet. In ApoE (-/-) mice treated with 1 mg/mL of sodium orthovanadate (NaOV), a specific inhibitor of tyrosine phosphatases including MKP-1, total phosphatase activity and MKP-1 protein were decreased in both the aortic lesions and liver lysates. In 3 animal models of atherosclerosis [C57BL6/J mice on an atherogenic diet for 15 weeks, LDLR (-/-) mice on a Western diet for 10 weeks, and ApoE (-/-) mice on a chow diet for 8 weeks], mice treated with NaOV had significantly smaller atherosclerotic lesions when compared with the control group. CONCLUSIONS: MKP-1 expression is associated with hypercholesterolemia and atherosclerosis, and inhibition of MKP-1 activity may prevent atherosclerotic lesion development in mice. MKP-1 is required for Ox-PAPC-mediated endothelial/monocyte interactions; however, an in vivo role of MKP-1 in atherogenesis has not been investigated. We now report that MKP-1 protein is expressed in the atherosclerotic lesions of mice and inhibition of tyrosine phosphatase activity and MKP-1 protein reduce atherosclerotic lesions in mouse models. |
