| First Author | Csányi G | Year | 2012 |
| Journal | Prostaglandins Other Lipid Mediat | Volume | 98 |
| Issue | 3-4 | Pages | 107-15 |
| PubMed ID | 22465673 | Mgi Jnum | J:318121 |
| Mgi Id | MGI:6858330 | Doi | 10.1016/j.prostaglandins.2012.02.002 |
| Citation | Csanyi G, et al. (2012) Functional alterations in endothelial NO, PGI(2) and EDHF pathways in aorta in ApoE/LDLR-/- mice. Prostaglandins Other Lipid Mediat 98(3-4):107-15 |
| abstractText | Adequate endothelial production of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), and prostacyclin (PGI(2)) is critical to the maintenance of vascular homeostasis. However, it is not clear whether alterations in each of these vasodilatory pathways contribute to the impaired endothelial function in murine atherosclerosis. In the present study, we analyze the alterations in NO-, EDHF- and PGI(2)-dependent endothelial function in the thoracic aorta in relation to the development of atherosclerotic plaques in apoE/LDLR(-)/(-) mice. We found that in the aorta of 2-month-old apoE/LDLR(-)/(-) mice there was no lipid deposition, subendothelial macrophage accumulation; and matrix metalloproteinase (MMP) activity was low, consistent with the absence of atherosclerotic plaques. Interestingly, at this stage the endothelium was already activated and hypertrophic as evidenced by electron microscopy, while acetylcholine-induced NO-dependent relaxation in the thoracic aorta was impaired, with concomitant upregulation of cyclooxygenase-2 (COX-2)/PGI(2) and EDHF (epoxyeicosatrienoic acids, EETs) pathways. In the aorta of 3-6-month-old apoE/LDLR(-)/(-) mice, lipid deposition, macrophage accumulation and MMP activity in the intima were gradually increased, while impairment of NO-dependent function and compensatory upregulation of COX-2/PGI(2) and EDHF pathways were more accentuated. These results suggest that impairment of NO-dependent relaxation precedes the development of atherosclerosis in the aorta and early upregulation of COX-2/PGI(2) and EDHF pathways may compensate for the loss of the biological activity of NO. |
