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 Pyrogallol-Phloroglucinol-6 6-Bieckol on Attenuates High-Fat Diet-Induced Hypertension by Modulating Endothelial-to-Mesenchymal Transition in the Aorta of Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Myeongjoo Son ◽  
Seyeon Oh ◽  
Ji Tae Jang ◽  
Kuk Hui Son ◽  
Kyunghee Byun
Keyword(s):  
Endothelial Cells ◽  
High Fat Diet ◽  
Oxidized Ldl ◽  
Intima Media Thickness ◽  
Mesenchymal Cell ◽  
High Fat ◽  
Mesenchymal Transition ◽  
Induced Hypertension ◽  
Endothelial To Mesenchymal Transition

Endothelial-to-mesenchymal transition (EndMT), which is involved in the development of various cardiovascular diseases, is induced by dyslipidemia or obesity. In dyslipidemia, the increased levels of oxidized low-density lipoproteins (oxLDL) upregulated the lectin-type oxidized LDL receptor 1 (Lox-1), which then upregulated the down signaling pathways of PKC-α/MMPs/TGF-β/SMAD2 or 3 and increased the EndMT. In this study, we investigated the effect of pyrogallol-phloroglucinol-6,6-bieckol (PPB), which is a compound of Ecklonia cava (E. cava), on decreased blood pressure (BP) by attenuating the EndMT in a high-fat diet- (HFD-) fed animal model. We also investigated PPB’s attenuation effect on EndMT in oxLDL-treated mouse endothelial cells as an in vitro model. The results indicated that, in the aorta or endothelial cells of mice, the HFD or oxLDL treatment significantly increased the expression of Lox-1/PKC-α/MMP9/TGF-β/SMAD2/SMAD3. The PPB treatment significantly decreased its expression. In contrast, the HFD or oxLDL treatment significantly decreased the expression of the EC markers (PECAM-1 and vWF) while the PPB treatment significantly increased them. Moreover, the HFD or oxLDL treatment significantly increased the expression of the mesenchymal cell markers (α-SMA and vimentin) while PPB treatment significantly decreased them. PPB decreased the intima-media thickness and extracellular matrix amount of the aorta and attenuated the BP, which was increased by the HFD. In conclusion, PPB attenuated the upregulation of Lox-1/PKC-α/MMP9/TGF-β/SMAD2 and 3 and restored the EndMT in HFD-fed animals. Moreover, PPB showed a restoring effect on HFD-induced hypertension.

Abstract MP05: The Mechanism Of The Pvat Pro-inflammatory Micro-environment Formation During The Development Of High Fat Diet-induced Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Yining Jin ◽  
Omar Kana ◽  
Ramya Kumar ◽  
Rance Nault ◽  
Hannah Garver ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
High Fat Diet ◽  
Cell Activation ◽  
Control Diet ◽  
Rna Seq ◽  
High Fat ◽  
Induced Hypertension ◽  
Th17 Differentiation

There is considerable evidence for a causative role for T cells in hypertension, including studies with immunosuppressive drugs and T cell-deficient models. Our previous studies showed that soluble mediators from mesenteric perivascular adipose tissue (mPVAT) modulate T cell function. Specifically, conditioned media from mPVAT (mPVAT-CM) from Dahl S rats on a high fat diet (HFD) promoted expression of the pro-inflammatory cytokines, IFNg, IL-17a and GM-CSF, by activated T cells. Furthermore, the Dahl S rats on HFD will later develop hypertension. Hypothesis: mPVAT is stimulated to produce immunomodulatory mediators that promotes Th1/17 differentiation preceding the development of HFD-induced hypertension. We conducted bulk RNA-seq on activated splenocytes cultured in mPVAT-CM from Dahl S rats on either control or HFD for 10 weeks. In accordance with our previous studies, PVAT-CM from HFD-fed rats significantly upregulated many genes associated with IFNg/IL-17 induction, including Mpeg1, Lyz2 and Tnfsf4 (5.0±1.78, 3.70±0.53 and 1.78±0.42 fold over Control diet, respectively). In contrast, Th2/Treg-associated genes, such as Ctla2a (-0.27±0.02) and Ccr4 (-0.41±0.03) were downregulated. We also performed single cell (sc) RNA-seq on the PVAT stromal vascular fraction (SVF) and found that acute inflammatory genes were enriched in the HFD group. Together with the bulk RNA-seq on mPVAT, these data strongly suggest that the pro-inflammatory mPVAT micro-environment may promote Th1/Th17 differentiation. To identify mediators in PVAT-CM that may induce Th1/Th17 differentiation, we compared the bulk RNA-seq on splenocytes cultured in PVAT-CM with bulk RNA-seq conducted on the whole mPVAT itself. We found that a T cell co-stimulatory receptor DPP4 (CD26), which is closely associated with T cell activation was significantly increased in mPVAT from HFD-fed rats (33.4±2.3 HFD vs. 15.3±1.8 Control diet). We also observed an increase in DPP4 global expression from mPVAT SVF in HFD-fed rats, as determined by scRNA-seq. Conclusion: The data suggest that HFD promotes the IFNg and IL-17a pathways in PVAT, which precedes hypertension in Dahl S rats and correlates with an increase in expression of DPP-4, a gene that promotes T cell activation. (NIH P01 HL070687).

scholarly journals Mycophenolate mofetil prevents high-fat diet-induced hypertension and renal glomerular injury in Dahl SS rats

2013 ◽  
Vol 1 (6) ◽  
Author(s):  
Frank T. Spradley ◽  
Carmen De Miguel ◽  
Janet Hobbs ◽  
David M. Pollock ◽  
Jennifer S. Pollock
Keyword(s):  
Mycophenolate Mofetil ◽  
High Fat Diet ◽  
Glomerular Injury ◽  
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 Intrarenal Ghrelin Receptor Antagonism Prevents High-Fat Diet-Induced Hypertension in Male Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (7) ◽  
pp. 2658-2666 ◽  
Author(s):  
Brandon A. Kemp ◽  
Nancy L. Howell ◽  
John J. Gildea ◽  
Shetal H. Padia
Keyword(s):  
Growth Hormone ◽  
High Fat Diet ◽  
Collecting Duct ◽  
Male Rats ◽  
Na Channel ◽  
Standard Diet ◽  
High Fat ◽  
Ghrelin Receptor ◽  
Induced Hypertension ◽  
Epithelial Na Channel

Excess weight gain contributes up to 65% of the risk of primary hypertension, and the increase in blood pressure in response to high-fat diet (HFD) is preceded by significant increases in renal tubular sodium (Na+) reabsorption. In normal rats, intrarenal ghrelin infusion increases distal nephron-dependent Na+ reabsorption via activation of the intrarenal ghrelin receptor (GHSR). This study focusses on the role of intrarenal GHSR-mediated Na+ reabsorption in HFD-induced hypertension. Dahl salt-sensitive rats received standard diet or HFD for 6 weeks. Rats underwent uninephrectomy and osmotic minipump implantation for chronic intrarenal delivery of vehicle (0.25 μL/h × 28 d), selective GHSR antagonist [D-Lys-3]-growth hormone releasing peptide-6 (0.2μM/d), or GHSR inverse agonist [D-Arg1, D-Phe5, D-Trp7,9, Leu11]-substance P (SUB-P) (3.6μM/d). HFD rats with vehicle pumps had significantly increased renal GHSR expression compared with standard diet (0.092 ± 0.005 vs 0.065 ± 0.004 arbitrary units; P < .05), whereas acyl ghrelin levels were similar (16.3±6.2 vs 15.7±8.7 pg/g tissue). HFD rats with vehicle pumps became hypertensive after 2 weeks (P < .05) and showed a significant reduction in 24-hour urine Na+ before hypertension. At this time, these rats showed an increase in collecting duct α-epithelial Na+ channel, thereby providing a potential mechanism for the excess Na+ reabsorption. In contrast, HFD rats with [D-Lys-3]-growth hormone releasing peptide-6 or SUB-P pumps never became hypertensive and did not show the reduction in urine Na+. Because SUB-P blocks the constitutive, but not ghrelin-dependent, activity of the GHSR, and HFD-induced α-epithelial Na+ channel up-regulation was abolished during GHSR antagonism, these data suggest that HFD increases the constitutive activity of renal GHSR to increase Na+ reabsorption and induce hypertension in rats.

Induction of Renal 20-Hydroxyeicosatetraenoic Acid by Clofibrate Attenuates High-Fat Diet-Induced Hypertension in Rats

2005 ◽  
Vol 317 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Yiqiang Zhou ◽  
Hui Huang ◽  
Hsin-Hsin Chang ◽  
Juan Du ◽  
Jing Feng Wu ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Hydroxyeicosatetraenoic Acid ◽  
High Fat ◽  
Induced Hypertension

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.

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