Apolipoprotein E in Hypercholesteremia and Beyond

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HomeStrokeVol. 38, No. 7Apolipoprotein E in Hypercholesteremia and Beyond Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBApolipoprotein E in Hypercholesteremia and Beyond Hans H. Dietrich, PhD Hans H. DietrichHans H. Dietrich From the Department of Neurological Surgery, Washington University Medical School, St. Louis, Mo. Search for more papers by this author Originally published24 May 2007https://doi.org/10.1161/STROKEAHA.107.489856Stroke. 2007;38:2036Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: May 24, 2007: Previous Version 1 See related article, pages 2136–2141.Apolipoprotein E (ApoE) is a protein related to the receptor-mediated removal of lipids from the blood stream. When ApoE-deficient mice were introduced,1,2 these animals displayed hypercholesteremia and increased atherosclerosis, providing a new tool to study hypercholesteremia-related pathological mechanisms and have been used extensively ever since. With respect to the cerebral circulation, it is interesting to note that not until 1998 did the first study on ApoE deficiency and cerebral ischemia appear3 and only 5 more studies, mostly related to stroke and inflammation, followed to this date in this field.Kitayama et al are interested to study the effect of hypercholesteremia on pial arteriolar vasomotor responses. They used hemizygous (ApoE+/−) animals as their control (rather than homozygotes) and ApoE-deficient mice (ApoE−/−) that were fed normal or high-fat diets. The first observation is that the hemizygous control animals have similar cholesterol levels as homozygous mice, indicating that one functioning allel of ApoE may be sufficient to keep blood cholesterol at normal levels. After demonstrating that especially severe hypercholesteremia adversely affects pial arteriolar dilation, the group continues to show that scavenging oxygen radicals with Tempol or inhibiting NADPH oxidase with Apocynin can restore vessel dilation to Acetylcholine at the lower concentration tested. But at the higher concentration used, Acetylcholine did not achieve dilation comparable to control animals. This seems to indicate that another factor besides oxygen radicals affects the vascular dilation to Acetylcholine in severely hypercholesteremic arterioles. If there is another factor and what this factor could be need to be studied further. Lack of response to external nitric oxide, though, does not seem to be deficient.Another aspect of the study of ApoE effects in mice is that we now have mouse models with the mouse ApoE gene replaced with human ApoE alleles. The study of such alleles has come to the forefront in many research areas including stroke and Alzheimer disease.4,5 Thus understanding and knowing the physiological effects of mouse ApoE will help us to determine the effects and consequences of introducing human ApoE alleles into this organism including vascular regulation. It is therefore possible that the observations and results provided by Kitayama et al will have implications beyond the study of hypercholesteremia.The opinions in this editorial are not necessarily those of the editors or of the American Heart Association.Sources of FundingH.H.D. is supported by NIH grants NS 32636, NS30555, and HL041250.DisclosuresNone.FootnotesCorrespondence to Hans H. Dietrich, Department of Neurological Surgery, Washington University Medical School, 660 South Euclid Avenue, St. Louis, MO 63110. E-mail [email protected] References 1 Zhang SH, Reddick RL, Piedrahita JA, Maeda N. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science. 1992; 258: 468–471.CrossrefMedlineGoogle Scholar2 Plump AS, Smith JD, Hayek T, alto-Setala K, Walsh A, Verstuyft JG, Rubin EM, Breslow JL. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell. 1992; 71: 343–353.CrossrefMedlineGoogle Scholar3 Bart RD, Sheng H, Laskowitz DT, Pearlstein RD, Warner DS. Regional CBF in apolipoprotein E-deficient and wild type mice during focal cerebral ischemia. Neuroreport. 1998; 9: 2615–2620.CrossrefMedlineGoogle Scholar4 Sudlow C, Martinez Gonzalez NA, Kim J, Clark C. Does apolipoprotein E genotype influence the risk of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage? Systematic review and meta-analyses of 31 studies among 5961 cases and 17,965 controls. Stroke. 2006; 37: 364–370.LinkGoogle Scholar5 Martins IJ, Hone E, Foster JK, Sunram-Lea SI, Gnjec A, Fuller SJ, Nolan D, Gandy SE, Martins RN. Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer’s disease and cardiovascular disease. Mol Psychiatry. 2006; 11: 721–736.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails July 2007Vol 38, Issue 7 Advertisement Article InformationMetrics https://doi.org/10.1161/STROKEAHA.107.489856PMID: 17525383 Originally publishedMay 24, 2007 PDF download Advertisement