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CARDIOVASCULAR RISK

Effects of Obesity and Weight Loss on the Functional Properties of Early Outgrowth Endothelial Progenitor Cells

Nana-Maria Heida, MD^_*, Jan-Peter Müller, MD^_*, I.-Fen Cheng, MSc^_*, Maren Leifheit-Nestler, PhD^_*, Vivien Faustin, PhD, Joachim Riggert, MD, Gerd Hasenfuss, MD^_*, Stavros Konstantinides, MD^_*,_* and Katrin Schäfer, MD^_*

^_* Department of Cardiology and Pulmonology, University of Göttingen, Göttingen, Germany
Department of Nutritional Psychology, University of Göttingen, Göttingen, Germany
Department of Transfusion Medicine, University of Göttingen, Göttingen, Germany

Manuscript received April 23, 2009; revised manuscript received August 20, 2009, accepted September 1, 2009.

^_* Reprint requests and correspondence: Dr. Stavros Konstantinides, Department of Cardiology, University General Hospital, 68100 Alexandroupolis, Greece (Email: skonst{at}med.duth.gr).

Objectives: The purpose of this study was to examine the impact of obesity and weight loss on the angiogenic and regenerative capacity of endothelial progenitor cells (EPCs).

Background: EPCs participate in angiogenesis and tissue repair. Several cardiovascular risk factors are associated with EPC dysfunction.

Methods: Early outgrowth EPCs were isolated from 49 obese (age 42 ± 14 years; body mass index 42 ± 7 kg/m²) normoglycemic participants in a professional weight reduction program and compared with those from 49 age-matched lean controls. EPC function was tested both in vitro and in vivo.

Results: EPCs expanded from the obese possessed reduced adhesive, migratory, and angiogenic capacity, and mice treated with obese EPCs exhibited reduced EPC homing in ischemic hind limbs in vivo. EPCs from the obese subjects failed to respond to conditioned medium of lean controls or to potent angiogenic factors such as vascular endothelial growth factor. Although no differences existed between lean and obese EPCs regarding the surface expression of vascular endothelial growth factor or chemokine receptors, basal p38 mitogen-activated protein kinase (MAPK) phosphorylation was elevated in obese EPCs (3.7 ± 2.1-fold increase; p = 0.006). These cells also showed reduced secretion of the angiogenic chemokines interleukin-8 (p = 0.047) and monocyte chemoattractant protein-1 (p = 0.012). By inhibiting p38 MAPK, we could restore chemokine levels to those of lean control EPCs and also improve the angiogenic properties of obese EPCs. Accordingly, 6-month follow-up of 26 obese persons who achieved significant weight reduction revealed normalization of p38 MAPK phosphorylation levels and improved EPC function.

Conclusions: Obesity is associated with a reversible functional impairment of EPCs. This involves reduced secretion of angiogenic chemokines and increased basal phosphorylation of signaling molecules, notably p38 MAPK.

Key Words: endothelial progenitor cells • obesity • signal transduction • weight loss

Abbreviations and Acronyms   BMI = body mass index   EPC = endothelial progenitor cell   MAPK = mitogen-activated protein kinase

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J. Am. Coll. Cardiol. 2010 55: A35-A33. [Full Text] [PDF]