211 IMPROVEMENTS IN ENDOTHELIAL CELL FUNCTION WITH PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR γ LIGAND, ROSIGLITAZONE.

2004 ◽  
Vol 52 (Suppl 1) ◽  
pp. S116.2-S116
Author(s):  
J Kim ◽  
S. Lee ◽  
M. Kim ◽  
J. Petrofsky ◽  
M. Laymon ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Endothelial Cell Function

CEPT1-Mediated Phospholipogenesis Regulates Endothelial Cell Function and Ischemia-Induced Angiogenesis Through PPARα

2020 ◽  
Author(s):  
Ada Admin ◽  
Mohamed A. Zayed ◽  
Xiaohua Jin ◽  
Chao Yang ◽  
Larisa Belaygorod ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
De Novo ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Tubule Formation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Endothelial Cell Function ◽  
Patients With Diabetes

<i>De novo</i> phosopholipogenesis, mediated by choline-ethanolamine phosphotransferase 1 (CEPT1), is essential for phospholipid activation of transcription factors such as peroxisome proliferator-activated receptor α (PPARα) in the liver. Fenofibrate, a PPARα agonist and lipid-lowering agent, decreases amputation incidence in patients with diabetes. Since we previously observed that CEPT1 is elevated in carotid plaque of patients with diabetes, we evaluated the role of CEPT1 in peripheral arteries and PPARα-phosphorylation (Ser12).<b> </b>CEPT1 was found to be elevated in diseased lower extremity arterial intima of individuals with peripheral arterial disease and diabetes. To evaluate the role of <i>Cept1</i> in the endothelium, we engineered a conditional endothelial cell (EC)-specific deletion of <i>Cept1</i> via induced <i>VE-cadherin-CreERT2 </i>mediated recombination (<i>Cept1Lp/LpCre+</i>). <i>Cept1Lp/LpCre+</i> ECs demonstrated decreased proliferation, migration, and tubule formation, and <i>Cept1Lp/LpCre+</i> mice had reduced perfusion and angiogenesis in ischemic hind-limbs. Peripheral ischemic recovery and PPARα signaling was further compromised by Streptozotocin-induced diabetes, and ameliorated by feeding fenofibrate. <i>Cept1</i> esiRNA decreased PPARα-phosphorylation in ECs, which was rescued with fenofibrate but not PC16:0/18:1. Unlike <i>Cept1Lp/LpCre+</i>, <i>Cept1Lp/LpCre+Ppara-/-</i> mice did not demonstrate hind-paw perfusion recovery after feeding fenofibrate.<b> </b>Therefore we demonstrate that CEPT1 is essential for EC function and tissue recovery following ischemia, and that fenofibrate rescues CEPT1-mediated activation of PPARα.

scholarly journals CEPT1-Mediated Phospholipogenesis Regulates Endothelial Cell Function and Ischemia-Induced Angiogenesis Through PPARα

2020 ◽  
Author(s):  
Ada Admin ◽  
Mohamed A. Zayed ◽  
Xiaohua Jin ◽  
Chao Yang ◽  
Larisa Belaygorod ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
De Novo ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Tubule Formation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Endothelial Cell Function ◽  
Patients With Diabetes

<i>De novo</i> phosopholipogenesis, mediated by choline-ethanolamine phosphotransferase 1 (CEPT1), is essential for phospholipid activation of transcription factors such as peroxisome proliferator-activated receptor α (PPARα) in the liver. Fenofibrate, a PPARα agonist and lipid-lowering agent, decreases amputation incidence in patients with diabetes. Since we previously observed that CEPT1 is elevated in carotid plaque of patients with diabetes, we evaluated the role of CEPT1 in peripheral arteries and PPARα-phosphorylation (Ser12).<b> </b>CEPT1 was found to be elevated in diseased lower extremity arterial intima of individuals with peripheral arterial disease and diabetes. To evaluate the role of <i>Cept1</i> in the endothelium, we engineered a conditional endothelial cell (EC)-specific deletion of <i>Cept1</i> via induced <i>VE-cadherin-CreERT2 </i>mediated recombination (<i>Cept1Lp/LpCre+</i>). <i>Cept1Lp/LpCre+</i> ECs demonstrated decreased proliferation, migration, and tubule formation, and <i>Cept1Lp/LpCre+</i> mice had reduced perfusion and angiogenesis in ischemic hind-limbs. Peripheral ischemic recovery and PPARα signaling was further compromised by Streptozotocin-induced diabetes, and ameliorated by feeding fenofibrate. <i>Cept1</i> esiRNA decreased PPARα-phosphorylation in ECs, which was rescued with fenofibrate but not PC16:0/18:1. Unlike <i>Cept1Lp/LpCre+</i>, <i>Cept1Lp/LpCre+Ppara-/-</i> mice did not demonstrate hind-paw perfusion recovery after feeding fenofibrate.<b> </b>Therefore we demonstrate that CEPT1 is essential for EC function and tissue recovery following ischemia, and that fenofibrate rescues CEPT1-mediated activation of PPARα.

Vascular smooth muscle cell dysfunction in diabetes: nuclear receptors channel to relaxation

2016 ◽  
Vol 130 (20) ◽  
pp. 1837-1839 ◽  
Author(s):  
Geneviève Doyon ◽  
Dennis Bruemmer
Keyword(s):  
Cell Function ◽  
Vascular Dysfunction ◽  
Microvascular Disease ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Endothelial Cell Function ◽  
Cell Dysfunction ◽  
Kv Channels ◽  
Voltage Dependent ◽  
Patients With Diabetes

Endothelial dysfunction and impaired vascular relaxation represent a common cause of microvascular disease in patients with diabetes. Although multiple mechanisms underlying altered endothelial cell function in diabetes have been described, there is currently no specific and approved pharmacological treatment. In this edition of Clinical Science, Morales-Cano et al. characterize voltage-dependent K+ (Kv) channels as genes regulated by pharmacological activation of peroxisome proliferator-activated receptor-b/d (PPARb/d). Diabetes altered Kv channel function leading to impaired coronary artery relaxation, which was prevented by pharmacological activation of PPARb/d. These studies highlight an important mechanism of vascular dysfunction in diabetes and point to a potential approach for therapy, particularly considering that PPARb/d ligands have been developed and tested in small clinical trials.

Do DPP-4 inhibitors improve endothelial cell function?

2017 ◽  
Vol 01 (01) ◽  
Author(s):  
Hiroshi Nomoto ◽  
Hideaki Miyoshi ◽  
Akinobu Nakamura ◽  
Tatsuya Atsumi ◽  
Naoki Manda ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
Endothelial Cell Function

Estrogen Restores Endothelial Cell Function in an Experimental Model of Vascular Injury

Circulation ◽  
1997 ◽  
Vol 96 (5) ◽  
pp. 1624-1630 ◽  
Author(s):  
C. Roger White ◽  
Jonathan Shelton ◽  
Shi-Juan Chen ◽  
Victor Darley-Usmar ◽  
Leslie Allen ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Experimental Model ◽  
Vascular Injury ◽  
Cell Function ◽  
Endothelial Cell Function

scholarly journals Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

2017 ◽  
Vol 232 (1) ◽  
pp. R27-R44 ◽  
Author(s):  
D S Boeldt ◽  
I M Bird
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Cell Function ◽  
Endothelial Cell Dysfunction ◽  
Hypertensive Disorders Of Pregnancy ◽  
Endothelial Cell Function ◽  
Vascular Adaptation ◽  
Cell Dysfunction ◽  
Maternal Adaptation ◽  
Flow Through

Maternal vascular adaptation to pregnancy is critically important to expand the capacity for blood flow through the uteroplacental unit to meet the needs of the developing fetus. Failure of the maternal vasculature to properly adapt can result in hypertensive disorders of pregnancy such as preeclampsia (PE). Herein, we review the endocrinology of maternal adaptation to pregnancy and contrast this with that of PE. Our focus is specifically on those hormones that directly influence endothelial cell function and dysfunction, as endothelial cell dysfunction is a hallmark of PE. A variety of growth factors and cytokines are present in normal vascular adaptation to pregnancy. However, they have also been shown to be circulating at abnormal levels in PE pregnancies. Many of these factors promote endothelial dysfunction when present at abnormal levels by acutely inhibiting key Ca2+ signaling events and chronically promoting the breakdown of endothelial cell–cell contacts. Increasingly, our understanding of how the contributions of the placenta, immune cells, and the endothelium itself promote the endocrine milieu of PE is becoming clearer. We then describe in detail how the complex endocrine environment of PE affects endothelial cell function, why this has contributed to the difficulty in fully understanding and treating this disorder, and how a focus on signaling convergence points of many hormones may be a more successful treatment strategy.

Shear stress regulates endothelial cell function through SRB1-eNOS signaling pathway

2016 ◽  
Vol 34 (5) ◽  
pp. 308-313 ◽  
Author(s):  
Ying Zhang ◽  
Bin Liao ◽  
Miaoling Li ◽  
Min Cheng ◽  
Yong Fu ◽  
...  
Keyword(s):  
Shear Stress ◽  
Endothelial Cell ◽  
Signaling Pathway ◽  
Cell Function ◽  
Endothelial Cell Function
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