Leptin Regulates Neointima Formation After Arterial Injury Through Mechanisms Independent of Blood Pressure and the Leptin Receptor/STAT3 Signaling Pathways Involved in Energy Balance

Bodary, Peter F.; Shen, Yuechun; Öhman, Miina K.; Bahrou, Kristina L.; Vargas, Fernando B.; Cudney, S. S.; Wickenheiser, Kevin J.; Myers, Martin G.; Eitzman, Daniel T.

doi:10.1161/01.atv.0000252068.89775.ee

Cited by 59 publications

(58 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although elevated leptin concentrations are associated with the intima-media thickness of the common carotid artery in obese patients and that treatment with leptin promotes neointimal formation, [14][15][16] our present studies did not detect the correlation between the circulating leptin levels with neointimal thickening in DIO mice model. In addition, the metabolic intracellular mechanisms by which DIO modulates NADPH oxidase activation and ROS formation, whether free fatty acids and insulin p47 phox attenuates carotid arterial flow cessation-induced angiogenic, inflammatory response and neointimal formation in DIO mice.…”

Section: Disscussioncontrasting

confidence: 79%

See 1 more Smart Citation

Critical role of the NADPH oxidase subunit p47phox on vascular TLR expression and neointimal lesion formation in high-fat diet-induced obesity

Chen

Stinnett

2008

Laboratory Investigation

View full text Add to dashboard Cite

Reactive oxygen species (ROS) formation is associated with inflammation and vasculature dysfunction. We investigated the potential role of the NADPH oxidase on vascular Toll-like receptor (TLR) expression and carotid neointimal formation in high-fat (HF) diet-induced obesity (DIO) model. Using mice DIO and common carotid artery flow cessation-induced lesion formation models, we examined vascular TLR2 and TLR4 expression and neointimal formation in NADPH oxidase subunit p47 phox -deficient (p47 phox-/-) mice. Feeding C57BL/6J mice an HF diet for 22 weeks resulted in significant increases in p47 phox , TLR2 and TLR4 expression in vascular tissues compared with mice fed a low-fat (LF) diet. Minimal changes in TLR2 and TLR4 expression was detected in p47 phox-/-DIO mice. Furthermore, flow cessation-induced angiogenic and inflammatory response and neointimal formation were significantly attenuated in p47 phoxÀ/À DIO mice compared with wild-type DIO mice. In addition, exposure of endothelial cells to leptin led to ROS formation; this was accompanied by upregulation of TLR2, TLR4 expression and its downstream signaling. Leptin also increased endothelial cell migration and proliferation. Pharmacological inhibition of NADPH oxidase or genetic deletion of p47 phox significantly diminished these alterations. Obesity increases neointimal formation via a mechanism involving p47 phox -TLRs signaling, suggesting that the NADPH oxidase may represent a potential novel therapeutic target for the treatment of obesity-associated vascular inflammation and dysfunction.

show abstract

Section: Disscussioncontrasting

confidence: 79%

“…[12][13][14][15] A recent study has revealed that treatment with leptin enhances neointimal lesion formation. 16 The role of NADPH oxidase in leptin-induced ROS formation, inflammation and endothelial cell dysfunction are not fully understood.…”

mentioning

confidence: 99%

Critical role of the NADPH oxidase subunit p47phox on vascular TLR expression and neointimal lesion formation in high-fat diet-induced obesity

Chen

Stinnett

2008

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…Ob/ObR-b axis contributes to the excessive PA-SMCs proliferation in iPAH Transgenic mice lacking Ob (ob/ob) or its receptor ObR (db/db) are known to be protected from neointima formation in response to vascular injury, whereas exogenous administration of Ob promotes experimental lesion formation in a receptor-specific manner [6,8,32,33]. Based on this knowledge, we tested whether Ob/ ObR-b axis could play similar roles in pulmonary vascular remodelling in iPAH.…”

Section: Resultsmentioning

confidence: 99%

Leptin signalling system as a target for pulmonary arterial hypertension therapy

Huertas

Thuillet

et al. 2015

Eur Respir J

View full text Add to dashboard Cite

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

show abstract

“…The leptin receptor is expressed not only in the hypothalamus but also in a variety of peripheral tissues (Friedman and Halaas, 1998). There is considerable evidence that leptin plays a role in the pathophysiology of acute and chronic inflammatory diseases, such as bacterial infection, atherosclerosis, and tissue fibrosis (La Cava and Matarese, 2004;Bodary et al, 2007;Tanaka et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Role of Central Leptin Signaling in the Starvation-Induced Alteration of B-Cell Development

Tanaka

Suganami²,

Kim-Saijo³

et al. 2011

Journal of Neuroscience

View full text Add to dashboard Cite

Leptin Regulates Neointima Formation After Arterial Injury Through Mechanisms Independent of Blood Pressure and the Leptin Receptor/STAT3 Signaling Pathways Involved in Energy Balance

Abstract: Background-Leptin is an adipocyte-derived hormone critical for energy homeostasis and implicated in vascular disease processes.

Cited by 59 publications

References 35 publications

Critical role of the NADPH oxidase subunit p47phox on vascular TLR expression and neointimal lesion formation in high-fat diet-induced obesity

Critical role of the NADPH oxidase subunit p47phox on vascular TLR expression and neointimal lesion formation in high-fat diet-induced obesity

Leptin signalling system as a target for pulmonary arterial hypertension therapy

Role of Central Leptin Signaling in the Starvation-Induced Alteration of B-Cell Development

Contact Info

Product

Resources

About