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Plaque-associated endothelial dysfunction in apolipoprotein E-deficient mice on a regular diet. Effect of human apolipoprotein AI.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Crauwels, Herta M. Hove, Cor E. Van Holvoet, Paul Herman, Arnold G. Bult, Hidde |
| Copyright Year | 2003 |
| Abstract | OBJECTIVE Apolipoprotein E-deficient mice (apoE(-/-)) on a regular diet become hypercholesterolemic and develop atherosclerosis, but endothelium-dependent relaxation remains undisturbed for up to 6 months. We investigated whether vasomotor dysfunction develops in aged apoE(-/-), whether the defect was systemic (hypercholesterolemia-dependent) or focal (plaque-related), and the effect of human apolipoprotein AI transgenesis (apoAI/E(-/-)). METHODS Arteries of apoE(-/-) (n=5), apoAI/E(-/-) (n=6) and C57Bl/6J (WT, n=4) mice (18 months) were systematically dissected for isometric tension recording and subsequent morphometry. RESULTS Acetylcholine (ACh)-induced relaxation was impaired (P<0.01) in atherosclerotic segments of apoE(-/-) (26+/-14%) as compared to WT mice (93+/-2%). Similar reduced (P<0.01) responses to adenosine 5'-triphosphate (apoE(-/-) 38+/-14, WT 94+/-3%) and the calcium ionophore A23187 (apoE(-/-) 19+/-6%, WT 97+/-2%) pointed to a post-receptor defect. Indeed, responses to exogenous nitric oxide were impaired in atherosclerotic segments as well (apoE(-/-) 71+/-7%, WT 92+/-1%, P<0.05). Furthermore, relaxations inversely correlated with plaque size (ACh r(s)=-0.74, P<0.01). In adjacent plaque-free segments however, responses to ACh (apoE(-/-) 92+/-3%, WT 97+/-1%) and all other agents were preserved, despite the prolonged hypercholesterolemia. ApoAI improved vasomotor responses in atherosclerotic segments. However, negative correlations between maximal relaxation and plaque area remained in apoAI/E(-/-) mice (ACh r(s)=-0.67, P<0.01). Indeed, covariate analysis of variance did not point to direct protection of vasomotor function by apoAI when the smaller lesions were taken into account. CONCLUSIONS Endothelial dysfunction in apoE(-/-) mice is not affected by hypercholesterolemia alone, but is strictly associated with plaque formation. Human apoAI transgenesis-known to raise HDL-attenuated atherogenesis, thereby indirectly improving relaxation responses in apoE(-/-) mice. |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/S0008-6363(03)00353-5 |
| Alternate Webpage(s) | https://watermark.silverchair.com/59-1-189.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAb0wggG5BgkqhkiG9w0BBwagggGqMIIBpgIBADCCAZ8GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMxhBW0hVP94Pwf6OYAgEQgIIBcJpe-1qN61tKmMEICus7hm9vt8MsAHF28LQ2xMMN0GDESbDft6u7HwBsJPR9icWrs6E6PC7P3byzxCAioIXbXS2WDqRj0gGg-MMcYvsBud5Fi9Injh1ArA7RUoWW_Weca0OIzAEVxfWcJ30GSE1WZUmINEe2NR2fC8EQY9st6uv6Egr6SpIzHCVLl0hSHRod6i2UXcP3Erg6KXxapGWFzau7ANSLqSThpVosUfi25n4uGXmq-JHjUZot3BFaRUUrSvD2JF1Q5btlUuSRUf1K16J_PRCMLfwpkLGwEAG39wyGgbwhpNnJgEIgoubJHGU_IBavR1DeLbAKcHjOrH5J7WGFSg3_gnQvIw8fCk66xtzU9utlz79n1s6sLbjka_IN-GHGfKcyk0yKL-Ai1mfALtmyKbNla7dWAI2_oTswJTJB9sIiVD58ueyJQoqN4Ei-7eWp-qNn6qasx50fJ9MDsL6-gIGO13mCBF83QWHg1A-k |
| PubMed reference number | 12829190 |
| Alternate Webpage(s) | https://doi.org/10.1016/S0008-6363%2803%2900353-5 |
| Journal | Medline |
| Volume Number | 59 |
| Issue Number | 1 |
| Journal | Cardiovascular research |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
