Leptin Enhances the Recruitment of Endothelial Progenitor Cells Into Neointimal Lesions After Vascular Injury by Promoting Integrin-Mediated Adhesion

Schroeter, Marco R.; Leifheit, Maren; Sudholt, Philipp; Heida, Nana-Maria; Dellas, Claudia; Rohm, Ilonka; Alves, Frauke; Zientkowska, Marta; Rafail, Stavros; Puls, Miriam; Hasenfuß, Gerd; Konstantinides, Stavros; Schäfer, Katrin

doi:10.1161/circresaha.107.169375

Cited by 92 publications

(78 citation statements)

References 49 publications

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“…These observations are in line with a recent study by Schroeter et al 16 that detected by fluorescence microscopy a subendothelial homing of intravenously injected early EPCs, promoting the endothelial repair response in another model of carotid injury. Moreover, these observations are consistent with a recent study by Sieveking et al 17 suggesting that early EPCs promote the proangiogenic effects largely in a paracrine fashion.…”

Section: Discussionsupporting

confidence: 92%

Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Prehypertension

et al. 2010

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Abstract-Prehypertension is a highly frequent condition associated with an increased cardiovascular risk. Endothelial dysfunction is thought to promote the development of hypertension and vascular disease; however, underlying mechanisms remain to be further determined. The present study characterizes for the first time the in vivo endothelial repair capacity of early endothelial progenitor cells (EPCs) in patients with prehypertension/hypertension and examines its relation with endothelial function. Early EPCs were isolated from healthy subjects and newly diagnosed prehypertensive and hypertensive patients (nϭ52). In vivo endothelial repair capacity of EPCs was examined by transplantation into a nude mouse carotid injury model. EPC senescence was determined (RT-PCR of telomere length). NO and superoxide production of EPCs were measured using electron spin resonance spectroscopy analysis. CD34 ϩ /KDR ϩ mononuclear cells and circulating endothelial microparticles were examined by fluorescence-activated cell sorter analysis. Endothelium-dependent and -independent vasodilations were determined by high-resolution ultrasound. In vivo endothelial repair capacity of EPCs was substantially impaired in prehypertensive/hypertensive patients as compared with healthy subjects (re-endothelialized area: 15Ϯ3%/13Ϯ2% versus 28Ϯ3%; PϽ0.05 versus healthy subjects). Senescence of EPCs in prehypertension/hypertension was substantially increased, and NO production was markedly reduced. Moreover, reduced endothelial repair capacity of early EPCs was significantly related to an accelerated senescence of early EPCs and impaired endothelial function. The present study demonstrates for the first time that in vivo endothelial repair capacity of early EPCs is reduced in patients with prehypertension and hypertension, is related to EPC senescence and impaired endothelial function, and likely represents an early event in the development of hypertension. (Hypertension. 2010;55:1389-1397.)

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Section: Discussionsupporting

confidence: 92%

Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Prehypertension

et al. 2010

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“…The adipokine leptin, mainly known for its role in regulating human energy homeostasis and appetite (80), has several atherogenic, thrombotic, and angiogenic actions on cardiovascular homeostasis (81). In this regard, leptin enhances the migratory activity of CAC in normal-weight adults (82). In obese adults, leptin resistance of CAC can be defeated by weight loss (83).…”

Section: Cell-derived Markers Of Endothelial Damage and Repair In Obementioning

confidence: 99%

Childhood obesity–related endothelial dysfunction: an update on pathophysiological mechanisms and diagnostic advancements

et al. 2016

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“…Cells (early passages ⩽5) were placed in serum-free medium for 24 h and exposed with dimethyloxaloylglycine (DMOG, 0.25 mM) (Enzo Life Sciences, Villeurbanne, France), dichloroacetate (DCA, 5 mM) (Sigma-Aldrich, Lyon, France), and recombinant Ob (10 and 100 ng·mL ) and ten times more (100 ng·mL −1 ) were used, based on the literature [15][16][17]. Proliferation was assessed by 5-bromo-2-deoxyuridine (BrdU) incorporation [12].…”

Section: Subjectsmentioning

confidence: 99%

Leptin signalling system as a target for pulmonary arterial hypertension therapy

Huertas

Thuillet

et al. 2015

Eur Respir J

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Excessive proliferation of pulmonary arterial smooth muscle cells (PA-SMCs) and perivascular inflammation lead to pulmonary arterial hypertension (PAH) progression, but they are not specifically targeted by the current therapies. Since leptin (Ob) and its main receptor ObR-b contribute to systemic vascular cell proliferation and inflammation, we questioned whether targeting Ob/ObR-b axis would be an effective antiproliferative and anti-inflammatory strategy against PAH.In idiopathic PAH (iPAH), using human lung tissues and primary cell cultures (early passages ⩽5), we demonstrate that pulmonary endothelial cells (P-ECs) over produce Ob and that PA-SMCs overexpress ObR-b. Furthermore, we obtain evidence that Ob enhances proliferation of human PA-SMCs in vitro and increases right ventricular systolic pressure in Ob-treated mice in the chronic hypoxia-induced pulmonary hypertension (PH) model. Using human cells, we also show that Ob leads to monocyte activation and increases cell adhesion molecule expression levels in P-ECs. We also find that Ob/ObR-b axis contributes to PH susceptibility by using ObR-deficient rats, which display less severe hypoxia-induced PH ( pulmonary haemodynamics, arterial muscularisation, PA-SMC proliferation and perivascular inflammation). Importantly, we demonstrate the efficacy of two curative strategies using a soluble Ob neutraliser and dichloroacetate in hypoxia-induced PH.We demonstrate here that Ob/ObR-b axis may represent anti-proliferative and anti-inflammatory targets in PAH. @ERSpublications Targeting Ob/ObR-b axis represents an important tool for anti-proliferative and antiinflammatory strategies in PH http://ow.ly/I00jh

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Leptin Enhances the Recruitment of Endothelial Progenitor Cells Into Neointimal Lesions After Vascular Injury by Promoting Integrin-Mediated Adhesion

Abstract: Abstract-The

Cited by 92 publications

References 49 publications

Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Prehypertension

Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Prehypertension

Childhood obesity–related endothelial dysfunction: an update on pathophysiological mechanisms and diagnostic advancements

Leptin signalling system as a target for pulmonary arterial hypertension therapy

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