Effects of preadipocytes derived from mice fed with high fat diet on the angiogenic potential of endothelial cells

2018 ◽  
Vol 28 (9) ◽  
pp. 937-943
Author(s):  
R.C. Castiglione ◽  
C.M.L. Barbosa ◽  
L.F.M. Prota ◽  
S.R. Marques-Neto ◽  
M. Perri-Oliveira ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Fat Diet ◽  
High Fat ◽  
Angiogenic Potential

scholarly journals PPAR? in endothelial cells influences high fat diet-induced hypertension

2005 ◽  
Vol 18 (4) ◽  
pp. 549-556 ◽  
Author(s):  
C NICOL ◽  
M ADACHI ◽  
T AKIYAMA ◽  
F GONZALEZ
Keyword(s):  
Endothelial Cells ◽  
High Fat Diet ◽  
High Fat ◽  
Induced Hypertension

scholarly journals Single-cell transcriptome analysis reveals cellular heterogeneity in the ascending aortas of normal and high-fat diet-fed mice

2021 ◽  
Vol 53 (9) ◽  
pp. 1379-1389
Author(s):  
Hao Kan ◽  
Ka Zhang ◽  
Aiqin Mao ◽  
Li Geng ◽  
Mengru Gao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Single Cell ◽  
High Fat Diet ◽  
Cell Types ◽  
Ascending Aorta ◽  
Normal Diet ◽  
Cellular Heterogeneity ◽  
Cellular Composition ◽  
High Fat ◽  
Aortic Diseases

AbstractThe aorta contains numerous cell types that contribute to vascular inflammation and thus the progression of aortic diseases. However, the heterogeneity and cellular composition of the ascending aorta in the setting of a high-fat diet (HFD) have not been fully assessed. We performed single-cell RNA sequencing on ascending aortas from mice fed a normal diet and mice fed a HFD. Unsupervised cluster analysis of the transcriptional profiles from 24,001 aortic cells identified 27 clusters representing 10 cell types: endothelial cells (ECs), fibroblasts, vascular smooth muscle cells (SMCs), immune cells (B cells, T cells, macrophages, and dendritic cells), mesothelial cells, pericytes, and neural cells. After HFD intake, subpopulations of endothelial cells with lipid transport and angiogenesis capacity and extensive expression of contractile genes were defined. In the HFD group, three major SMC subpopulations showed increased expression of extracellular matrix-degradation genes, and a synthetic SMC subcluster was proportionally increased. This increase was accompanied by upregulation of proinflammatory genes. Under HFD conditions, aortic-resident macrophage numbers were increased, and blood-derived macrophages showed the strongest expression of proinflammatory cytokines. Our study elucidates the nature and range of the cellular composition of the ascending aorta and increases understanding of the development and progression of aortic inflammatory disease.

scholarly journals Cystathionine γ-lyase protects vascular endothelium: a role for inhibition of histone deacetylase 6

2017 ◽  
Vol 312 (4) ◽  
pp. H711-H720 ◽  
Author(s):  
Thorsten M. Leucker ◽  
Yohei Nomura ◽  
Jae Hyung Kim ◽  
Anil Bhatta ◽  
Victor Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Histone Deacetylase ◽  
Vascular Endothelium ◽  
High Fat Diet ◽  
Histone Deacetylases ◽  
Molecular Mechanisms ◽  
Oxidized Ldl ◽  
Hdac Inhibitors ◽  
Histone Deacetylase 6 ◽  
High Fat

Endothelial cystathionine γ-lyase (CSEγ) contributes to cardiovascular homeostasis, mainly through production of H2S. However, the molecular mechanisms that control CSEγ gene expression in the endothelium during cardiovascular diseases are unclear. The aim of the current study is to determine the role of specific histone deacetylases (HDACs) in the regulation of endothelial CSEγ. Reduced CSEγ mRNA expression and protein abundance were observed in human aortic endothelial cells (HAEC) exposed to oxidized LDL (OxLDL) and in aortas from atherogenic apolipoprotein E knockout (ApoE−/−) mice fed a high-fat diet compared with controls. Intact murine aortic rings exposed to OxLDL (50 μg/ml) for 24 h exhibited impaired endothelium-dependent vasorelaxation that was blocked by CSEγ overexpression or the H2S donor NaHS. CSEγ expression was upregulated by pan-HDAC inhibitors and by class II-specific HDAC inhibitors, but not by other class-specific inhibitors. The HDAC6 selective inhibitor tubacin and HDAC6-specific siRNA increased CSEγ expression and blocked OxLDL-mediated reductions in endothelial CSEγ expression and CSEγ promoter activity, indicating that HDAC6 is a specific regulator of CSEγ expression. Consistent with this finding, HDAC6 mRNA, protein expression, and activity were upregulated in OxLDL-exposed HAEC, but not in human aortic smooth muscle cells. HDAC6 protein levels in aortas from high-fat diet-fed ApoE−/− mice were comparable to those in controls, whereas HDAC6 activity was robustly upregulated. Together, our findings indicate that HDAC6 is upregulated by atherogenic stimuli via posttranslational modifications and is a critical regulator of CSEγ expression in vascular endothelium. Inhibition of HDAC6 activity may improve endothelial function and prevent or reverse the development of atherosclerosis. NEW & NOTEWORTHY Oxidative injury to endothelial cells by oxidized LDL reduced cystathionine γ-lyase (CSEγ) expression and H2S production, leading to endothelial dysfunction, which was prevented by histone deacetylase 6 (HDAC6) inhibition. Our data suggest HDAC6 as a novel therapeutic target to prevent the development of atherosclerosis.

scholarly journals CYP2J2 Targeting to Endothelial Cells Attenuates Adiposity and Vascular Dysfunction in Mice Fed a High-Fat Diet by Reprogramming Adipocyte Phenotype

Hypertension ◽  
2014 ◽  
Vol 64 (6) ◽  
pp. 1352-1361 ◽  
Author(s):  
Nader G. Abraham ◽  
Komal Sodhi ◽  
Anne M. Silvis ◽  
Luca Vanella ◽  
Gaia Favero ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Fat Diet ◽  
Vascular Dysfunction ◽  
High Fat

scholarly journals Toll-like receptor 2 mediates high-fat diet-induced impairment of vasodilator actions of insulin

2013 ◽  
Vol 304 (10) ◽  
pp. E1077-E1088 ◽  
Author(s):  
Hyun-Ju Jang ◽  
Hae-Suk Kim ◽  
Daniel H. Hwang ◽  
Michael J. Quon ◽  
Jeong-a Kim
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
High Fat Diet ◽  
Saturated Fatty Acids ◽  
Cardiovascular Complications ◽  
Mesenteric Arteries ◽  
High Fat ◽  
Proinflammatory Response ◽  
Proinflammatory Responses ◽  
Sirna Knockdown

Obesity is characterized by a chronic proinflammatory state that leads to endothelial dysfunction. Saturated fatty acids (SFA) stimulate Toll-like receptors (TLR) that promote metabolic insulin resistance. However, it is not known whether TLR2 mediates impairment of vascular actions of insulin in response to high-fat diet (HFD) to cause endothelial dysfunction. siRNA knockdown of TLR2 in primary endothelial cells opposed palmitate-stimulated expression of proinflammatory cytokines and splicing of X box protein 1 (XBP-1). Inhibition of unfolding protein response (UPR) reduced SFA-stimulated expression of TNFα. Thus, SFA stimulates UPR and proinflammatory response through activation of TLR2 in endothelial cells. Knockdown of TLR2 also opposed impairment of insulin-stimulated phosphorylation of eNOS and subsequent production of NO. Importantly, insulin-stimulated vasorelaxation of mesenteric arteries from TLR2 knockout mice was preserved even on HFD (in contrast with results from arteries examined in wild-type mice on HFD). We conclude that TLR2 in vascular endothelium mediates HFD-stimulated proinflammatory responses and UPR that accompany impairment of vasodilator actions of insulin, leading to endothelial dysfunction. These results are relevant to understanding the pathophysiology of the cardiovascular complications of diabetes and obesity.

scholarly journals Renal microvascular damaged in diabetes mellitus with hyperlipidemia through the regulation of MAMs by PACS2 in endothelial cell

2021 ◽  
Author(s):  
Zhihao Shu ◽  
Shuhua Chen ◽  
Hong Xiang ◽  
Ruoru Wu ◽  
Shaoli Zhao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Cells ◽  
Fatty Acid ◽  
Endothelial Cell ◽  
Mouse Model ◽  
Vascular Permeability ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Kidney Tissue ◽  
High Fat

Abstract Background: The prevalence of diabetic vascular complications is rapidly increasing, especially in the diabetes mellitus with hyperlipidemia. Consistent hyperglycemia and hyperlipidemia impairs microvascular, but lack of effective intervention target to prevention or reduced the risk of serious bad ending. Methods: A mouse model of diabetes combined with hyperlipidemia were established by STZ injection and high fat diet to observe the possible damage of HGHF to renal blood vessels include vascular permeability, fibrosis and subcellular structure. Then, we replicated an in vitro endothelial cell injury model treated by 30mm Glucose and 0.1mm palmitic acid to verify its main functional changes. Proteomics and metabolomics were used to explore the molecular mechanisms behind diabetic microvascular damage. The mechanisms were further verified at siRNA interference and transgenic knockout mice. Results: We found that renal vascular permeability impaired and fibrosis increased significantly in the stz+HFD mice. In human umbilical vein endothelial cells (HUVECs) treated with high glucose/high fat (HGHF), the number of mitochondrial-associated membranes (MAMs) and the expression of phosphofurin acidic cluster sorting protein 2 (PACS2) increased. In particular, gene manipulation of PACS2 altered endothelial cell MAMs. Knocking down PACS2 restored the barrier function of HUVECs. In vivo, knocking out PACS2 ameliorated the kidney injury in diabetic mice induced by streptozotocin and fed with high-fat diet for up to 20 weeks. PACS2-/- mice leaked less vascular Evan’s blue and improved glomerular fibrosis in the kidney tissue of hyperglycemia and hyperlipidemia mouse model. We further observed the reduction of fatty acid β-oxidation (FAO), CPT1α expression, and NADPH production in endothelial cells induced by HGHF. These changes in fatty acid metabolism were rescued by silencing PACS2, but were blocked by the FAO inhibitor, etomoxir. Conclusion: PACS2 impacts the metabolic response of endothelial cells to HGHF through MAMs. Loss of PACS2 expression reduces glomerular endothelial cells barrier injury, induced by VE-Cadherin internalized under HGHF. PACS2 play a metabolism and MAMs regulators in the vascular endothelial cells of diabetes with hyperlipidemia.

Sign in / Sign up

Export Citation Format

Share Document