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Research Article

Vascular effects of a low-carbohydrate high-protein diet

Shi Yin Foo, Eric R. Heller, Joanna Wykrzykowska, Christopher J. Sullivan, Jennifer J. Manning-Tobin, Kathryn J. Moore, Robert E. Gerszten, and Anthony Rosenzweig
PNAS first published August 24, 2009; https://doi.org/10.1073/pnas.0907995106
Shi Yin Foo
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Eric R. Heller
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Joanna Wykrzykowska
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Christopher J. Sullivan
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Jennifer J. Manning-Tobin
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Kathryn J. Moore
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Robert E. Gerszten
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Anthony Rosenzweig
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  • For correspondence: arosenzw@bidmc.harvard.edu
  1. Communicated by Bruce M. Spiegelman, Harvard Medical School, Boston, MA, July 17, 2009 (received for review May 15, 2008)

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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.

  • atherosclerosis
  • dietary interventions
  • progenitor cells
  • neovascularization

Footnotes

  • 1To whom correspondence should be addressed at: Cardiovascular Division, Beth Israel Deaconess Medical Center, RW-456, 330 Brookline Avenue, Boston, MA 02215. E-mail: arosenzw{at}bidmc.harvard.edu
  • Author contributions: S.Y.F. and A.R. designed research; E.R.H., J.W., C.J.S., J.J.M.-T., and K.J.M. performed research; R.E.G. contributed new reagents/analytic tools; S.Y.F., K.J.M., R.E.G., and A.R. analyzed data; and S.Y.F. and A.R. wrote the paper.

  • The authors declare no conflict of interest.

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Vascular effects of a low-carbohydrate high-protein diet
Shi Yin Foo, Eric R. Heller, Joanna Wykrzykowska, Christopher J. Sullivan, Jennifer J. Manning-Tobin, Kathryn J. Moore, Robert E. Gerszten, Anthony Rosenzweig
Proceedings of the National Academy of Sciences Aug 2009, pnas.0907995106; DOI: 10.1073/pnas.0907995106

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Vascular effects of a low-carbohydrate high-protein diet
Shi Yin Foo, Eric R. Heller, Joanna Wykrzykowska, Christopher J. Sullivan, Jennifer J. Manning-Tobin, Kathryn J. Moore, Robert E. Gerszten, Anthony Rosenzweig
Proceedings of the National Academy of Sciences Aug 2009, pnas.0907995106; DOI: 10.1073/pnas.0907995106
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