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.

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Acknowledgments.

We thank Dr. Emerson Liu and Dr. Kenneth Cohen for technical advice and Dr. Serafima Zaltsman for expertly managing the mouse colony. S.Y.F. is a trainee of the Clinical Investigators Training Program: Beth Israel Deaconess Medical Center – Harvard/Massachusetts Institute of Technology Health Sciences and Technology, in collaboration with Pfizer Inc. and Merck and Co. This work was supported by a Leducq Foundation Network of Research Excellence (R.E.G., A.R.), an American Heart Association Grant-in-Aid (R.E.G.), and grants from the National Institutes of Health (A.R., R.E.G.) A.R. also gratefully acknowledges support from Judith and David Ganz and the Maxwell Hurston Charitable Foundation. A.R. is a principal faculty member of the Harvard Stem Cell Institute.

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Information & Authors

Information

Published in

The cover image for PNAS Vol.106; No.36
Proceedings of the National Academy of Sciences
Vol. 106 | No. 36
September 8, 2009
PubMed: 19706393

Classifications

Submission history

Received: May 15, 2008
Published online: September 8, 2009
Published in issue: September 8, 2009

Keywords

  1. atherosclerosis
  2. dietary interventions
  3. progenitor cells
  4. neovascularization

Acknowledgments

We thank Dr. Emerson Liu and Dr. Kenneth Cohen for technical advice and Dr. Serafima Zaltsman for expertly managing the mouse colony. S.Y.F. is a trainee of the Clinical Investigators Training Program: Beth Israel Deaconess Medical Center – Harvard/Massachusetts Institute of Technology Health Sciences and Technology, in collaboration with Pfizer Inc. and Merck and Co. This work was supported by a Leducq Foundation Network of Research Excellence (R.E.G., A.R.), an American Heart Association Grant-in-Aid (R.E.G.), and grants from the National Institutes of Health (A.R., R.E.G.) A.R. also gratefully acknowledges support from Judith and David Ganz and the Maxwell Hurston Charitable Foundation. A.R. is a principal faculty member of the Harvard Stem Cell Institute.

Notes

This article contains supporting information online at www.pnas.org/cgi/content/full/0907995106/DCSupplemental.

Authors

Affiliations

Shi Yin Foo
Cardiovascular Division of the Beth Israel Deaconess Medical Center CardioVascular Institute and Harvard Medical School, Boston, MA 02215;
Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; and
Eric R. Heller
Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; and
Joanna Wykrzykowska
Cardiovascular Division of the Beth Israel Deaconess Medical Center CardioVascular Institute and Harvard Medical School, Boston, MA 02215;
Christopher J. Sullivan
Cardiovascular Division of the Beth Israel Deaconess Medical Center CardioVascular Institute and Harvard Medical School, Boston, MA 02215;
Jennifer J. Manning-Tobin
Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; and
Kathryn J. Moore
Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; and
Robert E. Gerszten
Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; and
Anthony Rosenzweig1 [email protected]
Cardiovascular Division of the Beth Israel Deaconess Medical Center CardioVascular Institute and Harvard Medical School, Boston, MA 02215;
Harvard Stem Cell Institute, Cambridge, MA 02138

Notes

1
To whom correspondence should be addressed at: Cardiovascular Division, Beth Israel Deaconess Medical Center, RW-456, 330 Brookline Avenue, Boston, MA 02215. E-mail: [email protected]
Communicated by Bruce M. Spiegelman, Harvard Medical School, Boston, MA, July 17, 2009
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.

Competing Interests

The authors declare no conflict of interest.

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    Vascular effects of a low-carbohydrate high-protein diet
    Proceedings of the National Academy of Sciences
    • Vol. 106
    • No. 36
    • pp. 15093-15514

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