Vascular effects of a low-carbohydrate high-protein diet.
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.
Foo
Shi Yin
SY
Cardiovascular Division of the Beth Israel Deaconess Medical Center, CardioVascular Institute, Harvard Medical School, Boston, MA 02215, USA.
Heller
Eric R
ER
Wykrzykowska
Joanna
J
Sullivan
Christopher J
CJ
Manning-Tobin
Jennifer J
JJ
Moore
Kathryn J
KJ
Gerszten
Robert E
RE
Rosenzweig
Anthony
A
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
D001057:Apolipoproteins E; D004044:Dietary Proteins; D002784:Cholesterol; D051057:Proto-Oncogene Proteins c-akt
Science. 1997 Feb 14;275(5302):964-7
9020076
Atherosclerosis. 1997 Jun;131 Suppl:S3-4
9253466
Circulation. 2003 Sep 23;108(12):1520-6
12952850
Atherosclerosis. 2009 Jul;205(1):80-6
19111830
Atherosclerosis. 2002 Feb;160(2):377-84
11849661
Circulation. 2003 Dec 23;108(25):3115-21
14676142
Circulation. 2003 Jul 29;108(4):457-63
12860902
J Clin Endocrinol Metab. 2006 Jul;91(7):2542-7
16595593
Hypertension. 2008 Feb;51(2):376-82
18195164
Circ Res. 2006 Oct 13;99(8):e74-83
16990568
J Clin Invest. 1999 Mar;103(6):773-8
10079097
Nat Med. 2003 Nov;9(11):1370-6
14556003
Stroke. 2004 Oct;35(10):2378-84
15345801
Nat Med. 1999 Apr;5(4):434-8
10202935
Mol Cell. 1998 Aug;2(2):275-81
9734366
N Engl J Med. 2003 Feb 13;348(7):593-600
12584367
Cell. 1992 Oct 16;71(2):343-53
1423598
Diabetes. 2003 Dec;52(12):2882-7
14633847
Proc Natl Acad Sci U S A. 1992 May 15;89(10):4471-5
1584779
J Clin Invest. 1991 Oct;88(4):1121-7
1843454
N Engl J Med. 2003 May 22;348(21):2074-81
12761364
J Biol Chem. 1999 Jun 4;274(23):16349-54
10347193
Stem Cells. 2008 May;26(5):1376-84
18308946
Adv Exp Med Biol. 2003;522:17-24
12674207
J Clin Invest. 2000 Jun;105(11):1527-36
10841511
N Engl J Med. 2005 Sep 8;353(10):999-1007
16148285
Circ Res. 1999 Aug 6;85(3):221-8
10436164
Circulation. 2008 Apr 8;117(14):1856-63
18378610
J Clin Invest. 2001 Aug;108(3):391-7
11489932
Arterioscler Thromb Vasc Biol. 2007 Aug;27(8):1706-21
17541027
N Engl J Med. 2003 May 22;348(21):2082-90
12761365
Cell Metab. 2007 Jun;5(6):426-37
17550778
Am J Med Sci. 2002 Jan;323(1):3-10
11814139
N Engl J Med. 2005 Apr 21;352(16):1685-95
15843671
Atherosclerosis. 2008 Nov;201(1):36-42
18384792
Atherosclerosis. 1999 Aug;145(2):301-8
10488957