title: Vascular effects of a low-carbohydrate high-protein diet.
abstract: The cardiovascular complications of obesity have prompted interest in dietary interventions to reduce weight, including low-carbohydrate diets that are generally high in protein and fat. However, little is known about the long-term effects of these diets on vascular health. We examined the cardiovascular effects of a low-carbohydrate, high-protein diet (LCHP) in the ApoE(-/-) mouse model of atherosclerosis and in a model of ischemia-induced neovascularization. Mice on a LCHP were compared with mice maintained on either the standard chow diet (SC) or the Western diet (WD) which contains comparable fat and cholesterol to the LCHP. LCHP-fed mice developed more aortic atherosclerosis and had an impaired ability to generate new vessels in response to tissue ischemia. These changes were not explained by alterations in serum cholesterol, inflammatory mediators or infiltrates, or oxidative stress. The LCHP diet substantially reduced the number of bone marrow and peripheral blood endothelial progenitor cells (EPCs), a marker of vascular regenerative capacity. EPCs from mice on a LCHP diet also manifest lower levels of activated (phosphorylated) Akt, a serine-threonine kinase important in EPC mobilization, proliferation, and survival. Taken together, these data demonstrate that in animal models LCHP diets have adverse vascular effects not reflected in serum markers and that nonlipid macronutrients can modulate vascular progenitor cells and pathophysiology.
authors.affiliation: Cardiovascular Division of the Beth Israel Deaconess Medical Center, CardioVascular Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Shi Yin
authors.initials: SY
authors.lastname: Foo
authors.forename: Eric R
authors.initials: ER
authors.lastname: Heller
authors.forename: Joanna
authors.initials: J
authors.lastname: Wykrzykowska
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sullivan
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Manning-Tobin
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Moore
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gerszten
authors.forename: Anthony
authors.initials: A
authors.lastname: Rosenzweig
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology*; D002784:Cholesterol / Q000097:blood; D002853:Chromatography, Liquid; D050528:Diet, Carbohydrate-Restricted / Q000009:adverse effects*; D004044:Dietary Proteins / Q000008:administration & dosage / Q000009:adverse effects*; D005434:Flow Cytometry; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects
chemical_list: D001057:Apolipoproteins E; D004044:Dietary Proteins; D002784:Cholesterol; D051057:Proto-Oncogene Proteins c-akt
references.citation: Science. 1997 Feb 14;275(5302):964-7
references.pmid: 9020076
references.citation: Atherosclerosis. 1997 Jun;131 Suppl:S3-4
references.pmid: 9253466
references.citation: Circulation. 2003 Sep 23;108(12):1520-6
references.pmid: 12952850
references.citation: Atherosclerosis. 2009 Jul;205(1):80-6
references.pmid: 19111830
references.citation: Atherosclerosis. 2002 Feb;160(2):377-84
references.pmid: 11849661
references.citation: Circulation. 2003 Dec 23;108(25):3115-21
references.pmid: 14676142
references.citation: Circulation. 2003 Jul 29;108(4):457-63
references.pmid: 12860902
references.citation: J Clin Endocrinol Metab. 2006 Jul;91(7):2542-7
references.pmid: 16595593
references.citation: Hypertension. 2008 Feb;51(2):376-82
references.pmid: 18195164
references.citation: Circ Res. 2006 Oct 13;99(8):e74-83
references.pmid: 16990568
references.citation: J Clin Invest. 1999 Mar;103(6):773-8
references.pmid: 10079097
references.citation: Nat Med. 2003 Nov;9(11):1370-6
references.pmid: 14556003
references.citation: Stroke. 2004 Oct;35(10):2378-84
references.pmid: 15345801
references.citation: Nat Med. 1999 Apr;5(4):434-8
references.pmid: 10202935
references.citation: Mol Cell. 1998 Aug;2(2):275-81
references.pmid: 9734366
references.citation: N Engl J Med. 2003 Feb 13;348(7):593-600
references.pmid: 12584367
references.citation: Cell. 1992 Oct 16;71(2):343-53
references.pmid: 1423598
references.citation: Diabetes. 2003 Dec;52(12):2882-7
references.pmid: 14633847
references.citation: Proc Natl Acad Sci U S A. 1992 May 15;89(10):4471-5
references.pmid: 1584779
references.citation: J Clin Invest. 1991 Oct;88(4):1121-7
references.pmid: 1843454
references.citation: N Engl J Med. 2003 May 22;348(21):2074-81
references.pmid: 12761364
references.citation: J Biol Chem. 1999 Jun 4;274(23):16349-54
references.pmid: 10347193
references.citation: Stem Cells. 2008 May;26(5):1376-84
references.pmid: 18308946
references.citation: Adv Exp Med Biol. 2003;522:17-24
references.pmid: 12674207
references.citation: J Clin Invest. 2000 Jun;105(11):1527-36
references.pmid: 10841511
references.citation: N Engl J Med. 2005 Sep 8;353(10):999-1007
references.pmid: 16148285
references.citation: Circ Res. 1999 Aug 6;85(3):221-8
references.pmid: 10436164
references.citation: Circulation. 2008 Apr 8;117(14):1856-63
references.pmid: 18378610
references.citation: J Clin Invest. 2001 Aug;108(3):391-7
references.pmid: 11489932
references.citation: Arterioscler Thromb Vasc Biol. 2007 Aug;27(8):1706-21
references.pmid: 17541027
references.citation: N Engl J Med. 2003 May 22;348(21):2082-90
references.pmid: 12761365
references.citation: Cell Metab. 2007 Jun;5(6):426-37
references.pmid: 17550778
references.citation: Am J Med Sci. 2002 Jan;323(1):3-10
references.pmid: 11814139
references.citation: N Engl J Med. 2005 Apr 21;352(16):1685-95
references.pmid: 15843671
references.citation: Atherosclerosis. 2008 Nov;201(1):36-42
references.pmid: 18384792
references.citation: Atherosclerosis. 1999 Aug;145(2):301-8
references.pmid: 10488957