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Reprogramming Dysfunctional Endothelial Progenitor Cells with PPARα-laden Microparticles

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Review of “Microparticles Carrying Peroxisome Proliferator-Activated Receptor Alpha Restore the Reduced Differentiation and Functionality of Bone Marrow-Derived Cells Induced by High-Fat Diet” from STEM CELLS TRANSLATIONAL MEDICINE by Stuart P. Atkinson

Studies have indicated that dysfunction of bone marrow (BM)-derived endothelial progenitor cells (EPCs) [1] may lead to the vascular endothelium damage associated with metabolic syndrome [2, 3]. Researchers from the laboratory of Maria Carmen Martinez (Université Angers, France) understood that peroxisome proliferator-activated receptor alpha (PPARα) protein carried in plasma membrane blebs known as microparticles (MPs) [4] can regulate EPC function in a healthy mouse model [5]. Their new STEM CELLS TRANSLATIONAL MEDICINE study now assesses whether PPARα-carrying MPs may represent a potential means to return loss function to EPCs in a mouse model of obesity and a new therapeutic option for metabolic syndrome in human patients [6].

Vergori et al. employed mice fed on a high-fat diet (HFD) as a model for obesity, discovering that altered diet prompted a reduction in the number of circulating EPCs and an impairment in the differentiation capacities of both BM-derived EPCs and monocytic progenitor cells. However, the authors discovered that treatment with MPs derived from wild-type mice, but not MPs derived from PPARα-deficient mice, permitted a recovery in the differentiation of both progenitor types and, importantly, in vivo angiogenesis. The authors highlight the importance of PPARα to this process, given the abolition of the improvements made by wild-type MPs following treatment with a specific inhibitor of PPARα.

The authors hope that treatment with PPARα-containing MPs may foster the formation of new blood vessels to improve the supply of oxygen and nutrients in affected tissues, therefore representing a safe and effective means of treating the symptoms of metabolic syndrome. However, the authors do note that just how PPARα affects EPC differentiation remains to be fully elucidated; stay tuned to the Stem Cells Portal to find out more!

References

  1. Kuliszewski MA, Ward MR, Kowalewski JW, et al., A direct comparison of endothelial progenitor cell dysfunction in rat metabolic syndrome and diabetes. Atherosclerosis 2013;226:58-66.
  2. Eckel RH, Alberti KG, Grundy SM, et al., The metabolic syndrome. Lancet 2010;375:181-3.
  3. Sorrentino SA, Bahlmann FH, Besler C, et al., Oxidant stress impairs in vivo reendothelialization capacity of endothelial progenitor cells from patients with type 2 diabetes mellitus: restoration by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. Circulation 2007;116:163-73.
  4. Leroyer AS, Ebrahimian TG, Cochain C, et al., Microparticles from ischemic muscle promotes postnatal vasculogenesis. Circulation 2009;119:2808-17.
  5. Benameur T, Tual-Chalot S, Andriantsitohaina R, et al., PPARalpha is essential for microparticle-induced differentiation of mouse bone marrow-derived endothelial progenitor cells and angiogenesis. PLoS One 2010;5:e12392.
  6. Vergori L, Lauret E, Soleti R, et al., Microparticles Carrying Peroxisome Proliferator-Activated Receptor Alpha Restore the Reduced Differentiation and Functionality of Bone Marrow-Derived Cells Induced by High-Fat Diet. Stem Cells Transl Med 2018;7:135-145.