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.
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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Received: May 15, 2008
Published online: September 8, 2009
Published in issue: September 8, 2009
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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.
Notes
This article contains supporting information online at www.pnas.org/cgi/content/full/0907995106/DCSupplemental.
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The authors declare no conflict of interest.
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Vascular effects of a low-carbohydrate high-protein diet, Proc. Natl. Acad. Sci. U.S.A.
106 (36) 15418-15423,
https://doi.org/10.1073/pnas.0907995106
(2009).
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