PUBLICATION
Chronological in vivo imaging reveals endothelial inflammation prior to neutrophils accumulation and lipid deposition in HCD-fed zebrafish
- Authors
- Luo, H., Li, Q.Q., Wu, N., Shen, Y.G., Liao, W.T., Yang, Y., Dong, E., Zhang, G.M., Liu, B.R., Yue, X.Z., Tang, X.Q., Yang, H.S.
- ID
- ZDB-PUB-191016-12
- Date
- 2019
- Source
- Atherosclerosis 290: 125-135 (Journal)
- Registered Authors
- Keywords
- Early inflammation, Hypercholesterolemia, Myeloid cells, Neutrophils, PPARĪ³, Zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Anti-Inflammatory Agents/pharmacology
- Atherosclerosis/genetics
- Atherosclerosis/metabolism*
- Atherosclerosis/pathology
- Atherosclerosis/prevention & control
- Cholesterol, Dietary*
- Disease Models, Animal
- Endothelial Cells/drug effects
- Endothelial Cells/metabolism*
- Endothelial Cells/pathology
- Human Umbilical Vein Endothelial Cells/metabolism
- Humans
- Hypercholesterolemia/drug therapy
- Hypercholesterolemia/genetics
- Hypercholesterolemia/metabolism*
- Hypercholesterolemia/pathology
- Inflammation/genetics
- Inflammation/metabolism*
- Inflammation/pathology
- Inflammation/prevention & control
- Interleukin-1beta/metabolism
- Lipid Metabolism*
- Microscopy, Confocal*
- Neutrophil Infiltration*
- PPAR gamma/agonists
- PPAR gamma/metabolism
- Plaque, Atherosclerotic
- Rosiglitazone/pharmacology
- Time Factors
- Tumor Necrosis Factor-alpha/metabolism
- Zebrafish
- Zebrafish Proteins/metabolism
- PubMed
- 31614249 Full text @ Atherosclerosis
Citation
Luo, H., Li, Q.Q., Wu, N., Shen, Y.G., Liao, W.T., Yang, Y., Dong, E., Zhang, G.M., Liu, B.R., Yue, X.Z., Tang, X.Q., Yang, H.S. (2019) Chronological in vivo imaging reveals endothelial inflammation prior to neutrophils accumulation and lipid deposition in HCD-fed zebrafish. Atherosclerosis. 290:125-135.
Abstract
Background and aims Hyperlipidemia-induced atherosclerosis is the major cause of heart attack and stroke in humans. However, pathological details and molecular mechanisms underlying early atherogenesis remain incompletely characterized. This study explored the early events of atherogenesis in a hypercholesterolemic zebrafish model in vivo.
Methods We used transparent transgenic zebrafish larvae Tg(lysc:EGFP), Tg(mpx:EGFP), Tg(mpeg1:EGFP), Tg(flk1:EGFP) or Tg(lysc:EGFP/flk1:mCherry), together with fluorescently labeled control and high cholesterol diets (HCD), to dynamically investigate the early development of atherosclerosis with confocal in vivo. Endothelial cells with green fluorescence were sorted by fluorescence-activated cell sorting (FACS) to detect gene expression. Moreover, we treated hypercholesterolemic zebrafish model in vivo or human umbilical vein endothelial cells (HUVEC) in vitro with rosiglitazone, an agonist of peroxisome proliferator-activated receptor γ (PPARγ).
Results We found that HCD-induced endothelial inflammation was an earlier pathological alteration than myeloid cells/neutrophils accumulation and lipid deposition in zebrafish vascular vessels of HCD-fed zebrafish. Endothelial inflammation was characterized by down-regulation of anti-inflammatory PPARγ and upregulation of pro-inflammatory tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β). Pharmacological treatment with rosiglitazone reversed the decrease in the expression of PPARγ and decreased expression of TNF-α and IL-1β in HCD-fed zebrafish. Moreover, rosiglitazone ameliorated myeloid cells accumulation and lipid deposition in HCD-fed zebrafish in vivo.
Conclusions Hyperlipidemia-induced endothelial inflammation happens earlier than myeloid cell neutrophils accumulation in vascular vessels, and neutrophils accumulation is prior to lipid deposition during the initial stage of atherosclerosis. Early alleviation of inflammation induced by HCD would have a prophylactic effect for the initial development of atherosclerosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping