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Title: Deficiency of cyclin-dependent kinase inhibitors p21{sup Cip1} and p27{sup Kip1} accelerates atherogenesis in apolipoprotein E-deficient mice

Abstract

Cyclin-dependent kinase inhibitors, p21{sup Cip1} and p27{sup Kip1}, are upregulated during vascular cell proliferation and negatively regulate growth of vascular cells. We hypothesized that absence of either p21{sup Cip1} or p27{sup Kip1} in apolipoprotein E (apoE)-deficiency may increase atherosclerotic plaque formation. Compared to apoE{sup -/-} aortae, both apoE{sup -/-}/p21{sup -/-} and apoE{sup -/-}/p27{sup -/-} aortae exhibited significantly more atherosclerotic plaque following a high-cholesterol regimen. This increase was particularly observed in the abdominal aortic regions. Deficiency of p27{sup Kip1} accelerated plaque formation significantly more than p21{sup -/-} in apoE{sup -/-} mice. This increased plaque formation was in parallel with increased intima/media area ratios. Deficiency of p21{sup Cip1} and p27{sup Kip1} accelerates atherogenesis in apoE{sup -/-} mice. These findings have significant implications for our understanding of the molecular basis of atherosclerosis associated with excessive proliferation of vascular cells.

Authors:
 [1];  [2]; ;  [1];  [3];  [1];  [1]
  1. National Human Genome Research Institute and National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892 (United States)
  2. (Sweden)
  3. Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Goeteborg, SE-405 30 (Sweden)
Publication Date:
OSTI Identifier:
22202615
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 396; Journal Issue: 2; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AORTA; ARTERIOSCLEROSIS; CELL PROLIFERATION; CHOLESTEROL; MICE; MONOCLINIC LATTICES; PLAQUE FORMATION

Citation Formats

Akyuerek, Levent M., Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Goeteborg, SE-405 30, Boehm, Manfred, Olive, Michelle, Zhou, Alex-Xianghua, San, Hong, and Nabel, Elizabeth G., E-mail: enabel@partners.org. Deficiency of cyclin-dependent kinase inhibitors p21{sup Cip1} and p27{sup Kip1} accelerates atherogenesis in apolipoprotein E-deficient mice. United States: N. p., 2010. Web. doi:10.1016/J.BBRC.2010.04.097.
Akyuerek, Levent M., Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Goeteborg, SE-405 30, Boehm, Manfred, Olive, Michelle, Zhou, Alex-Xianghua, San, Hong, & Nabel, Elizabeth G., E-mail: enabel@partners.org. Deficiency of cyclin-dependent kinase inhibitors p21{sup Cip1} and p27{sup Kip1} accelerates atherogenesis in apolipoprotein E-deficient mice. United States. doi:10.1016/J.BBRC.2010.04.097.
Akyuerek, Levent M., Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Goeteborg, SE-405 30, Boehm, Manfred, Olive, Michelle, Zhou, Alex-Xianghua, San, Hong, and Nabel, Elizabeth G., E-mail: enabel@partners.org. Fri . "Deficiency of cyclin-dependent kinase inhibitors p21{sup Cip1} and p27{sup Kip1} accelerates atherogenesis in apolipoprotein E-deficient mice". United States. doi:10.1016/J.BBRC.2010.04.097.
@article{osti_22202615,
title = {Deficiency of cyclin-dependent kinase inhibitors p21{sup Cip1} and p27{sup Kip1} accelerates atherogenesis in apolipoprotein E-deficient mice},
author = {Akyuerek, Levent M. and Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Goeteborg, SE-405 30 and Boehm, Manfred and Olive, Michelle and Zhou, Alex-Xianghua and San, Hong and Nabel, Elizabeth G., E-mail: enabel@partners.org},
abstractNote = {Cyclin-dependent kinase inhibitors, p21{sup Cip1} and p27{sup Kip1}, are upregulated during vascular cell proliferation and negatively regulate growth of vascular cells. We hypothesized that absence of either p21{sup Cip1} or p27{sup Kip1} in apolipoprotein E (apoE)-deficiency may increase atherosclerotic plaque formation. Compared to apoE{sup -/-} aortae, both apoE{sup -/-}/p21{sup -/-} and apoE{sup -/-}/p27{sup -/-} aortae exhibited significantly more atherosclerotic plaque following a high-cholesterol regimen. This increase was particularly observed in the abdominal aortic regions. Deficiency of p27{sup Kip1} accelerated plaque formation significantly more than p21{sup -/-} in apoE{sup -/-} mice. This increased plaque formation was in parallel with increased intima/media area ratios. Deficiency of p21{sup Cip1} and p27{sup Kip1} accelerates atherogenesis in apoE{sup -/-} mice. These findings have significant implications for our understanding of the molecular basis of atherosclerosis associated with excessive proliferation of vascular cells.},
doi = {10.1016/J.BBRC.2010.04.097},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 396,
place = {United States},
year = {Fri May 28 00:00:00 EDT 2010},
month = {Fri May 28 00:00:00 EDT 2010}
}