William C Sessa
Yale University
H-index: 132
North America-United States
Description
William C Sessa, With an exceptional h-index of 132 and a recent h-index of 59 (since 2020), a distinguished researcher at Yale University, specializes in the field of Vascular Biology, Pharmacology, Nitric Oxide.
His recent articles reflect a diverse array of research interests and contributions to the field:
Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice
1026 Plasminogen Activator Inhibitor 1 promotes endothelial cell inflammatory response
Macrophage-derived 25-hydroxycholesterol promotes vascular inflammation, atherogenesis, and lesion remodeling
TNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes
An optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells
Endothelial Nitric Oxide Synthase (eNOS) S1176 phosphorylation status governs atherosclerotic lesion formation
SREBP2 regulates the endothelial response to cytokines via direct transcriptional activation of KLF6
Genetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice
Professor Information
University | Yale University |
---|---|
Position | ___ |
Citations(all) | 71276 |
Citations(since 2020) | 14872 |
Cited By | 62527 |
hIndex(all) | 132 |
hIndex(since 2020) | 59 |
i10Index(all) | 326 |
i10Index(since 2020) | 239 |
University Profile Page | Yale University |
Research & Interests List
Vascular Biology
Pharmacology
Nitric Oxide
Top articles of William C Sessa
Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice
Blood vessels are continually exposed to circulating lipids, and elevation of ApoB-containing lipoproteins causes atherosclerosis. Lipoprotein metabolism is highly regulated by lipolysis, largely at the level of the capillary endothelium lining metabolically active tissues. How large blood vessels, the site of atherosclerotic vascular disease, regulate the flux of fatty acids (FAs) into triglyceride-rich (TG-rich) lipid droplets (LDs) is not known. In this study, we showed that deletion of the enzyme adipose TG lipase (ATGL) in the endothelium led to neutral lipid accumulation in vessels and impaired endothelial-dependent vascular tone and nitric oxide synthesis to promote endothelial dysfunction. Mechanistically, the loss of ATGL led to endoplasmic reticulum stress–induced inflammation in the endothelium. Consistent with this mechanism, deletion of endothelial ATGL markedly increased lesion size in a model of …
Authors
Nabil E Boutagy,Ana Gamez-Mendez,Joseph WM Fowler,Hanming Zhang,Bal K Chaube,Enric Esplugues,Andrew Kuo,Sungwoon Lee,Daiki Horikami,Jiasheng Zhang,Kathryn M Citrin,Abhishek K Singh,Brian G Coon,Monica Y Lee,Yajaira Suarez,Carlos Fernandez-Hernando,William C Sessa
Journal
The Journal of Clinical Investigation
Published Date
2024/2/15
1026 Plasminogen Activator Inhibitor 1 promotes endothelial cell inflammatory response
ObjectivePlasminogen Activator Inhibitor 1 (PAI1) is elevated in preeclampsia. In addition to its prothrombotic activity, emerging evidence suggests that PAI-1 directly contributes to endothelial dysfunction. Our objective was to determine whether PAI1 modulates the endothelial cell response to tumor necrosis factor alpha (TNFα), an inflammatory cytokine that is elevated in preeclampsia.Study DesignHuman umbilical vein endothelial cells (HUVECs) were transfected with PAI1-specific silencing RNA or non-targeting control, followed by treatment with TNFα (1 ng/mL) for 16 hours. In other experiments, HUVECs were treated with purified recombinant PAI1 (40 ng/μL) prior to TNFα. To rescue the phenotype, HUVECs were infected with a lentivirus that over-expresses PAI1 prior to RNA silencing and TNFα treatment. Gene expression was measured by reverse transcription polymerase chain reaction (RT-PCR). Protein …
Authors
Rachel Hauschel,Nabil Boutagy,William Sessa,Molly McAdow
Journal
American Journal of Obstetrics & Gynecology
Published Date
2024/1/1
Macrophage-derived 25-hydroxycholesterol promotes vascular inflammation, atherogenesis, and lesion remodeling
Background Cross-talk between sterol metabolism and inflammatory pathways has been demonstrated to significantly affect the development of atherosclerosis. Cholesterol biosynthetic intermediates and derivatives are increasingly recognized as key immune regulators of macrophages in response to innate immune activation and lipid overloading. 25-Hydroxycholesterol (25-HC) is produced as an oxidation product of cholesterol by the enzyme cholesterol 25-hydroxylase (CH25H) and belongs to a family of bioactive cholesterol derivatives produced by cells in response to fluctuating cholesterol levels and immune activation. Despite the major role of 25-HC as a mediator of innate and adaptive immune responses, its contribution during the progression of atherosclerosis remains unclear. Methods The levels of 25-HC were analyzed by liquid chromatography-mass spectrometry, and the expression of CH25H in …
Authors
Alberto Canfrán-Duque,Noemi Rotllan,Xinbo Zhang,Irene Andrés-Blasco,Bonne M Thompson,Jonathan Sun,Nathan L Price,Marta Fernández-Fuertes,Joseph W Fowler,Diego Gómez-Coronado,William C Sessa,Chiara Giannarelli,Robert J Schneider,George Tellides,Jeffrey G McDonald,Carlos Fernández-Hernando,Yajaira Suárez
Journal
Circulation
Published Date
2023/1/31
TNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes
The endothelium is a major target of the proinflammatory cytokine, tumor necrosis factor alpha (TNFα). Exposure of endothelial cells (EC) to proinflammatory stimuli leads to an increase in mitochondrial metabolism; however, the function and regulation of elevated mitochondrial metabolism in EC in response to proinflammatory cytokines remain unclear. Studies using high-resolution metabolomics and 13C-glucose and 13C-glutamine labeling flux techniques showed that pyruvate dehydrogenase activity (PDH) and oxidative tricarboxylic acid cycle (TCA) flux are elevated in human umbilical vein ECs in response to overnight (16 h) treatment with TNFα (10 ng/mL). Mechanistic studies indicated that TNFα mediated these metabolic changes via mitochondrial-specific protein degradation of pyruvate dehydrogenase kinase 4 (PDK4, inhibitor of PDH) by the Lon protease via an NF-κB-dependent mechanism. Using RNA …
Authors
Nabil E Boutagy,Joseph W Fowler,Kariona A Grabinska,Rebecca Cardone,Qiushi Sun,Kyla R Vazquez,Michael B Whalen,Xiaolong Zhu,Raja Chakraborty,Kathleen A Martin,Michael Simons,Casey E Romanoski,Richard G Kibbey,William C Sessa
Journal
Proceedings of the National Academy of Sciences
Published Date
2023/9/19
An optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells
The serine/threonine kinase AKT is a central node in cell signaling. While aberrant AKT activation underlies the development of a variety of human diseases, how different patterns of AKT-dependent phosphorylation dictate downstream signaling and phenotypic outcomes remains largely enigmatic. Herein, we perform a systems-level analysis that integrates methodological advances in optogenetics, mass spectrometry-based phosphoproteomics, and bioinformatics to elucidate how different intensity, duration, and pattern of Akt1 stimulation lead to distinct temporal phosphorylation profiles in vascular endothelial cells. Through the analysis of ~35,000 phosphorylation sites across multiple conditions precisely controlled by light stimulation, we identify a series of signaling circuits activated downstream of Akt1 and interrogate how Akt1 signaling integrates with growth factor signaling in endothelial cells. Furthermore …
Authors
Wenping Zhou,Wenxue Li,Shisheng Wang,Barbora Salovska,Zhenyi Hu,Bo Tao,Yi Di,Ujwal Punyamurtula,Benjamin E Turk,William C Sessa,Yansheng Liu
Journal
Nature Communications
Published Date
2023/6/26
Endothelial Nitric Oxide Synthase (eNOS) S1176 phosphorylation status governs atherosclerotic lesion formation
ObjectiveWe have previously demonstrated the in vivo importance of the Akt-eNOS substrate-kinase relationship, as defective postnatal angiogenesis characteristic of global Akt1-null mice is rescued when bred to ‘gain-of-function’eNOS S1176D mutant mice. While multiple studies support the vascular protective role of endothelial NO generation, the causal role of Akt1-dependent eNOS S1176 phosphorylation during atherosclerotic plaque formation is not yet clear.
Authors
Tung D Nguyen,Nur-Taz Rahman,William C Sessa,Monica Y Lee
Journal
Frontiers in Cardiovascular Medicine
Published Date
2023
SREBP2 regulates the endothelial response to cytokines via direct transcriptional activation of KLF6
The transcription factor SREBP2 is the main regulator of cholesterol homeostasis and is central to the mechanism of action of lipid-lowering drugs, such as statins, which are responsible for the largest overall reduction in cardiovascular risk and mortality in humans with atherosclerotic disease. Recently, SREBP2 has been implicated in leukocyte innate and adaptive immune responses by upregulation of cholesterol flux or direct transcriptional activation of pro-inflammatory genes. Here, we investigate the role of SREBP2 in endothelial cells (ECs), since ECs are at the interface of circulating lipids with tissues and crucial to the pathogenesis of cardiovascular disease. Loss of SREBF2 inhibits the production of pro-inflammatory chemokines but amplifies type I interferon response genes in response to inflammatory stimulus. Furthermore, SREBP2 regulates chemokine expression not through enhancement of …
Authors
Joseph Wayne M Fowler,Nabil E Boutagy,Rong Zhang,Daiki Horikami,Michael B Whalen,Casey E Romanoski,William C Sessa
Journal
Journal of Lipid Research
Published Date
2023/8/1
Genetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice
Low-density lipoprotein (LDL) accumulation in the arterial wall contributes to atherosclerosis initiation and progression. Activin A receptor-like type 1 (ACVRL1, called activin-like kinase receptor (ALK1)) is a recently identified receptor that mediates LDL entry and transcytosis in endothelial cells (ECs),. However, the role of this pathway in vivo is not yet known. In the present study, we show that genetic deletion of ALK1 in arterial ECs of mice substantially limits LDL accumulation, macrophage infiltration and atherosclerosis without affecting cholesterol or triglyceride levels. Moreover, a selective monoclonal antibody binding ALK1 efficiently blocked LDL transcytosis, but not bone morphogenetic protein-9 (BMP9) signaling, dramatically reducing plaque formation in LDL receptor knockout mice fed a high-fat diet. Thus, our results demonstrate that blocking LDL transcytosis into the endothelium may be a promising …
Authors
Sungwoon Lee,Hubertus Schleer,Hyojin Park,Erika Jang,Michael Boyer,Bo Tao,Ana Gamez-Mendez,Abhishek Singh,Ewa Folta-Stogniew,Xinbo Zhang,Lingfeng Qin,Xue Xiao,Lin Xu,Junhui Zhang,Xiaoyue Hu,Evanthia Pashos,George Tellides,Philip W Shaul,Warren L Lee,Carlos Fernandez-Hernando,Anne Eichmann,William C Sessa
Journal
Nature cardiovascular research
Published Date
2023/5
Professor FAQs
What is William C Sessa's h-index at Yale University?
The h-index of William C Sessa has been 59 since 2020 and 132 in total.
What are William C Sessa's top articles?
The articles with the titles of
Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice
1026 Plasminogen Activator Inhibitor 1 promotes endothelial cell inflammatory response
Macrophage-derived 25-hydroxycholesterol promotes vascular inflammation, atherogenesis, and lesion remodeling
TNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes
An optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells
Endothelial Nitric Oxide Synthase (eNOS) S1176 phosphorylation status governs atherosclerotic lesion formation
SREBP2 regulates the endothelial response to cytokines via direct transcriptional activation of KLF6
Genetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice
...
are the top articles of William C Sessa at Yale University.
What are William C Sessa's research interests?
The research interests of William C Sessa are: Vascular Biology, Pharmacology, Nitric Oxide
What is William C Sessa's total number of citations?
William C Sessa has 71,276 citations in total.
What are the co-authors of William C Sessa?
The co-authors of William C Sessa are Kenneth Walsh, Jordan S. Pober, Giuseppe Cirino, Andreas Papapetropoulos, George Tellides, themis Kyriakides.