Improvement of endothelial function with dietary flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease

Christian Heiss, Sarah Jahn, Melanie Taylor, Wendy May Real, Franca S. Angeli, Maelene L. Wong, Nicolas Amabile, Megha Prasad, Tienush Rassaf, Javier I. Ottaviani, Shirley Mihardja, Carl L Keen, Matthew L. Springer, Andrew Boyle, William Grossman, Stanton A. Glantz, Hagen Schroeter, Yerem Yeghiazarians

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Objectives: In patients with coronary artery disease (CAD) medically managed according to currently accepted guidelines, we tested whether a 1-month dietary intervention with flavanol-containing cocoa leads to an improvement of endothelial dysfunction and whether this is associated with an enhanced number and function of circulating angiogenic cells (CACs). Background: Dietary flavanols can improve endothelial dysfunction. The CACs, also termed endothelial progenitor cells, are critical for vascular repair and maintenance of endothelial function. Methods: In a randomized, controlled, double-masked, cross-over trial, 16 CAD patients (64 ± 3 years of age) received a dietary high-flavanol intervention (HiFI [375 mg]) and a macronutrient- and micronutrient-matched low-flavanol intervention (LoFI [9 mg]) twice daily in random order over 30 days. Results: Endothelium-dependent vasomotor function, as measured by flow-mediated vasodilation of the brachial artery, improved by 47% in the HiFI period compared with the LoFI period. After HiFI, the number of CD34+/KDR+-CACs, as measured by flow cytometry, increased 2.2-fold as compared with after LoFI. The CAC functions, as measured by the capacity to survive, differentiate, proliferate, and to migrate were not different between the groups. The HiFI led to a decrease in systolic blood pressure (mean change over LoFI: -4.2 ± 2.7 mm Hg), and increase in plasma nitrite level (mean change over LoFI: 74 ± 32 nM). Applying a mixed-effects linear regression model, the results demonstrated a significant increase in flow-mediated vasodilation and a decrease in systolic blood pressure with increasing levels of CD34+/KDR+-CACs. Conclusions: Sustained improvements in endothelial dysfunction by regular dietary intake of flavanols are associated with mobilization of functional CACs. (Effect of Cocoa Flavanols on Vascular Function in Optimally Treated Coronary Artery Disease Patients: Interaction Between Endothelial Progenitor Cells, Reactivity of Micro- and Macrocirculation; NCT00553774).

Original languageEnglish (US)
Pages (from-to)218-224
Number of pages7
JournalJournal of the American College of Cardiology
Volume56
Issue number3
DOIs
StatePublished - Jul 13 2010

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Coronary Artery Disease
Blood Pressure
Vasodilation
Blood Vessels
Linear Models
Brachial Artery
Micronutrients
Microcirculation
Nitrites
Cross-Over Studies
Endothelium
Flow Cytometry
Maintenance
Guidelines
Endothelial Progenitor Cells

Keywords

  • BA
  • brachial artery
  • CAC
  • CAD
  • circulating angiogenic cell
  • coronary artery disease
  • flow-mediated dilation
  • FMD
  • HiFI
  • high-flavanol intervention
  • LDL
  • LoFI
  • low-density lipoprotein
  • low-flavanol intervention
  • nitric oxide
  • NO
  • SCF
  • SDF
  • stem cell factor
  • stromal cell-derived factor
  • vascular endothelial growth factor
  • VEGF

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Improvement of endothelial function with dietary flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease. / Heiss, Christian; Jahn, Sarah; Taylor, Melanie; Real, Wendy May; Angeli, Franca S.; Wong, Maelene L.; Amabile, Nicolas; Prasad, Megha; Rassaf, Tienush; Ottaviani, Javier I.; Mihardja, Shirley; Keen, Carl L; Springer, Matthew L.; Boyle, Andrew; Grossman, William; Glantz, Stanton A.; Schroeter, Hagen; Yeghiazarians, Yerem.

In: Journal of the American College of Cardiology, Vol. 56, No. 3, 13.07.2010, p. 218-224.

Research output: Contribution to journalArticle

Heiss, C, Jahn, S, Taylor, M, Real, WM, Angeli, FS, Wong, ML, Amabile, N, Prasad, M, Rassaf, T, Ottaviani, JI, Mihardja, S, Keen, CL, Springer, ML, Boyle, A, Grossman, W, Glantz, SA, Schroeter, H & Yeghiazarians, Y 2010, 'Improvement of endothelial function with dietary flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease', Journal of the American College of Cardiology, vol. 56, no. 3, pp. 218-224. https://doi.org/10.1016/j.jacc.2010.03.039
Heiss, Christian ; Jahn, Sarah ; Taylor, Melanie ; Real, Wendy May ; Angeli, Franca S. ; Wong, Maelene L. ; Amabile, Nicolas ; Prasad, Megha ; Rassaf, Tienush ; Ottaviani, Javier I. ; Mihardja, Shirley ; Keen, Carl L ; Springer, Matthew L. ; Boyle, Andrew ; Grossman, William ; Glantz, Stanton A. ; Schroeter, Hagen ; Yeghiazarians, Yerem. / Improvement of endothelial function with dietary flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease. In: Journal of the American College of Cardiology. 2010 ; Vol. 56, No. 3. pp. 218-224.
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abstract = "Objectives: In patients with coronary artery disease (CAD) medically managed according to currently accepted guidelines, we tested whether a 1-month dietary intervention with flavanol-containing cocoa leads to an improvement of endothelial dysfunction and whether this is associated with an enhanced number and function of circulating angiogenic cells (CACs). Background: Dietary flavanols can improve endothelial dysfunction. The CACs, also termed endothelial progenitor cells, are critical for vascular repair and maintenance of endothelial function. Methods: In a randomized, controlled, double-masked, cross-over trial, 16 CAD patients (64 ± 3 years of age) received a dietary high-flavanol intervention (HiFI [375 mg]) and a macronutrient- and micronutrient-matched low-flavanol intervention (LoFI [9 mg]) twice daily in random order over 30 days. Results: Endothelium-dependent vasomotor function, as measured by flow-mediated vasodilation of the brachial artery, improved by 47{\%} in the HiFI period compared with the LoFI period. After HiFI, the number of CD34+/KDR+-CACs, as measured by flow cytometry, increased 2.2-fold as compared with after LoFI. The CAC functions, as measured by the capacity to survive, differentiate, proliferate, and to migrate were not different between the groups. The HiFI led to a decrease in systolic blood pressure (mean change over LoFI: -4.2 ± 2.7 mm Hg), and increase in plasma nitrite level (mean change over LoFI: 74 ± 32 nM). Applying a mixed-effects linear regression model, the results demonstrated a significant increase in flow-mediated vasodilation and a decrease in systolic blood pressure with increasing levels of CD34+/KDR+-CACs. Conclusions: Sustained improvements in endothelial dysfunction by regular dietary intake of flavanols are associated with mobilization of functional CACs. (Effect of Cocoa Flavanols on Vascular Function in Optimally Treated Coronary Artery Disease Patients: Interaction Between Endothelial Progenitor Cells, Reactivity of Micro- and Macrocirculation; NCT00553774).",
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author = "Christian Heiss and Sarah Jahn and Melanie Taylor and Real, {Wendy May} and Angeli, {Franca S.} and Wong, {Maelene L.} and Nicolas Amabile and Megha Prasad and Tienush Rassaf and Ottaviani, {Javier I.} and Shirley Mihardja and Keen, {Carl L} and Springer, {Matthew L.} and Andrew Boyle and William Grossman and Glantz, {Stanton A.} and Hagen Schroeter and Yerem Yeghiazarians",
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TY - JOUR

T1 - Improvement of endothelial function with dietary flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease

AU - Heiss, Christian

AU - Jahn, Sarah

AU - Taylor, Melanie

AU - Real, Wendy May

AU - Angeli, Franca S.

AU - Wong, Maelene L.

AU - Amabile, Nicolas

AU - Prasad, Megha

AU - Rassaf, Tienush

AU - Ottaviani, Javier I.

AU - Mihardja, Shirley

AU - Keen, Carl L

AU - Springer, Matthew L.

AU - Boyle, Andrew

AU - Grossman, William

AU - Glantz, Stanton A.

AU - Schroeter, Hagen

AU - Yeghiazarians, Yerem

PY - 2010/7/13

Y1 - 2010/7/13

N2 - Objectives: In patients with coronary artery disease (CAD) medically managed according to currently accepted guidelines, we tested whether a 1-month dietary intervention with flavanol-containing cocoa leads to an improvement of endothelial dysfunction and whether this is associated with an enhanced number and function of circulating angiogenic cells (CACs). Background: Dietary flavanols can improve endothelial dysfunction. The CACs, also termed endothelial progenitor cells, are critical for vascular repair and maintenance of endothelial function. Methods: In a randomized, controlled, double-masked, cross-over trial, 16 CAD patients (64 ± 3 years of age) received a dietary high-flavanol intervention (HiFI [375 mg]) and a macronutrient- and micronutrient-matched low-flavanol intervention (LoFI [9 mg]) twice daily in random order over 30 days. Results: Endothelium-dependent vasomotor function, as measured by flow-mediated vasodilation of the brachial artery, improved by 47% in the HiFI period compared with the LoFI period. After HiFI, the number of CD34+/KDR+-CACs, as measured by flow cytometry, increased 2.2-fold as compared with after LoFI. The CAC functions, as measured by the capacity to survive, differentiate, proliferate, and to migrate were not different between the groups. The HiFI led to a decrease in systolic blood pressure (mean change over LoFI: -4.2 ± 2.7 mm Hg), and increase in plasma nitrite level (mean change over LoFI: 74 ± 32 nM). Applying a mixed-effects linear regression model, the results demonstrated a significant increase in flow-mediated vasodilation and a decrease in systolic blood pressure with increasing levels of CD34+/KDR+-CACs. Conclusions: Sustained improvements in endothelial dysfunction by regular dietary intake of flavanols are associated with mobilization of functional CACs. (Effect of Cocoa Flavanols on Vascular Function in Optimally Treated Coronary Artery Disease Patients: Interaction Between Endothelial Progenitor Cells, Reactivity of Micro- and Macrocirculation; NCT00553774).

AB - Objectives: In patients with coronary artery disease (CAD) medically managed according to currently accepted guidelines, we tested whether a 1-month dietary intervention with flavanol-containing cocoa leads to an improvement of endothelial dysfunction and whether this is associated with an enhanced number and function of circulating angiogenic cells (CACs). Background: Dietary flavanols can improve endothelial dysfunction. The CACs, also termed endothelial progenitor cells, are critical for vascular repair and maintenance of endothelial function. Methods: In a randomized, controlled, double-masked, cross-over trial, 16 CAD patients (64 ± 3 years of age) received a dietary high-flavanol intervention (HiFI [375 mg]) and a macronutrient- and micronutrient-matched low-flavanol intervention (LoFI [9 mg]) twice daily in random order over 30 days. Results: Endothelium-dependent vasomotor function, as measured by flow-mediated vasodilation of the brachial artery, improved by 47% in the HiFI period compared with the LoFI period. After HiFI, the number of CD34+/KDR+-CACs, as measured by flow cytometry, increased 2.2-fold as compared with after LoFI. The CAC functions, as measured by the capacity to survive, differentiate, proliferate, and to migrate were not different between the groups. The HiFI led to a decrease in systolic blood pressure (mean change over LoFI: -4.2 ± 2.7 mm Hg), and increase in plasma nitrite level (mean change over LoFI: 74 ± 32 nM). Applying a mixed-effects linear regression model, the results demonstrated a significant increase in flow-mediated vasodilation and a decrease in systolic blood pressure with increasing levels of CD34+/KDR+-CACs. Conclusions: Sustained improvements in endothelial dysfunction by regular dietary intake of flavanols are associated with mobilization of functional CACs. (Effect of Cocoa Flavanols on Vascular Function in Optimally Treated Coronary Artery Disease Patients: Interaction Between Endothelial Progenitor Cells, Reactivity of Micro- and Macrocirculation; NCT00553774).

KW - BA

KW - brachial artery

KW - CAC

KW - CAD

KW - circulating angiogenic cell

KW - coronary artery disease

KW - flow-mediated dilation

KW - FMD

KW - HiFI

KW - high-flavanol intervention

KW - LDL

KW - LoFI

KW - low-density lipoprotein

KW - low-flavanol intervention

KW - nitric oxide

KW - NO

KW - SCF

KW - SDF

KW - stem cell factor

KW - stromal cell-derived factor

KW - vascular endothelial growth factor

KW - VEGF

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DO - 10.1016/j.jacc.2010.03.039

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C2 - 20620742

AN - SCOPUS:77955060311

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JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

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