Dysfunctional high density lipoprotein failed to rescue the function of oxidized low density lipoprotein-treated endothelial progenitor cells

a novel index for the prediction of HDL functionality

Chun Ming Shih, Feng Yen Lin, Jong Shiuan Yeh, Yi Wen Lin, Shih Hurng Loh, Nai Wen Tsao, Hironori Nakagami, Ryuichi Morishita, Tatsuya Sawamura, Chi Yuan Li, Cheng Yen Lin, Chun Yao Huang

研究成果: 雜誌貢獻文章

摘要

Lipid metabolic disorders play critical roles in atherogenesis. Traditionally, it has been suggested that reduced high density lipoprotein (HDL) levels might be an important morbidity indicator for cardiovascular diseases. Therefore, it has been argued that therapeutically raising HDL levels may reduce atherogenesis in patients with dyslipidemia. However, recent clinical trials to elevate serum HDL levels by pharmacologic approaches failed to demonstrate clinical efficacy. Thus, to investigate the functionality of HDL and to explore the possible clinical relevance as well as to define an effective indicator that can represent HDL function may provide another key and reference to disclose the clinical treatment of dyslipidemia. We analyzed the association between the data of dichlorofluorescein assay (assay the functionality of HDL), the effect of HDL on oxidized low density lipoprotein (oxLDL)-stimulated endothelial progenitor cells (EPCs) in vitro, levels of circulating EPCs, and ex vitro EPC colony forming units of each case, we defined the indicator (relative HDL index (RHDL index) = dichlorofluorescein assay result of each subject/dichlorofluorescein assay reading of our young healthy controls) that may represent functionality of HDL. HDL from healthy adults protected oxLDL-treated EPCs by modulating p38 mitogen-activated protein kinase and Rho activation and by promoting nitric oxide production. HDL from subject with RHDL index ≧2 also failed to restore the functionality of oxLDL-treated EPCs via cell-signaling pathways in vitro. The RHDL index significantly correlated with patients’ circulating EPC number or EPC colony forming units ex vivo. In conclusions, we explored the RHDL index as a score to predict a patient's EPC functions in vivo and ex vitro.
原文英語
頁(從 - 到)17-32
頁數16
期刊Translational Research
205
DOIs
出版狀態已發佈 - 三月 1 2019

指紋

Endothelial cells
HDL Lipoproteins
Assays
Dyslipidemias
Atherosclerosis
oxidized low density lipoprotein
Endothelial Progenitor Cells
Stem Cells
HDL2 Lipoprotein
Cell signaling
Specific Gravity
p38 Mitogen-Activated Protein Kinases
Reading
Nitric Oxide
Cardiovascular Diseases
Cell Count
Chemical activation
Association reactions
Clinical Trials
Morbidity

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Biochemistry, medical
  • Physiology (medical)

引用此文

Dysfunctional high density lipoprotein failed to rescue the function of oxidized low density lipoprotein-treated endothelial progenitor cells : a novel index for the prediction of HDL functionality. / Shih, Chun Ming; Lin, Feng Yen; Yeh, Jong Shiuan; Lin, Yi Wen; Loh, Shih Hurng; Tsao, Nai Wen; Nakagami, Hironori; Morishita, Ryuichi; Sawamura, Tatsuya; Li, Chi Yuan; Lin, Cheng Yen; Huang, Chun Yao.

於: Translational Research, 卷 205, 01.03.2019, p. 17-32.

研究成果: 雜誌貢獻文章

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title = "Dysfunctional high density lipoprotein failed to rescue the function of oxidized low density lipoprotein-treated endothelial progenitor cells: a novel index for the prediction of HDL functionality",
abstract = "Lipid metabolic disorders play critical roles in atherogenesis. Traditionally, it has been suggested that reduced high density lipoprotein (HDL) levels might be an important morbidity indicator for cardiovascular diseases. Therefore, it has been argued that therapeutically raising HDL levels may reduce atherogenesis in patients with dyslipidemia. However, recent clinical trials to elevate serum HDL levels by pharmacologic approaches failed to demonstrate clinical efficacy. Thus, to investigate the functionality of HDL and to explore the possible clinical relevance as well as to define an effective indicator that can represent HDL function may provide another key and reference to disclose the clinical treatment of dyslipidemia. We analyzed the association between the data of dichlorofluorescein assay (assay the functionality of HDL), the effect of HDL on oxidized low density lipoprotein (oxLDL)-stimulated endothelial progenitor cells (EPCs) in vitro, levels of circulating EPCs, and ex vitro EPC colony forming units of each case, we defined the indicator (relative HDL index (RHDL index) = dichlorofluorescein assay result of each subject/dichlorofluorescein assay reading of our young healthy controls) that may represent functionality of HDL. HDL from healthy adults protected oxLDL-treated EPCs by modulating p38 mitogen-activated protein kinase and Rho activation and by promoting nitric oxide production. HDL from subject with RHDL index ≧2 also failed to restore the functionality of oxLDL-treated EPCs via cell-signaling pathways in vitro. The RHDL index significantly correlated with patients’ circulating EPC number or EPC colony forming units ex vivo. In conclusions, we explored the RHDL index as a score to predict a patient's EPC functions in vivo and ex vitro.",
keywords = "ACS = acute coronary syndrome, ALT= alanine transaminase, APOI = apocynin, CAD = coronary artery disease, CETP = cholesterol ester transfer protein, DCFH-DA = 2′,7′-dichlorofluorescin diacetate, HDL = high density lipoprotein, HPODE = hydroperoxyoctadeca-9Z,11E-dienoic acid, MNC = mononuclear cell, NO = nitric oxide, PAH-AH = platelet-activating factor acetylhydrolase, PMA = phorbol 12-myristate 13-acetate, PON1 = paraoxonase-1, RHDL index = relative HDL index, TBARS = thiobarbituric acid reactive substance, TC = total cholesterol, TG = triglycerides, eNOS = endothelial nitric oxide synthase",
author = "Shih, {Chun Ming} and Lin, {Feng Yen} and Yeh, {Jong Shiuan} and Lin, {Yi Wen} and Loh, {Shih Hurng} and Tsao, {Nai Wen} and Hironori Nakagami and Ryuichi Morishita and Tatsuya Sawamura and Li, {Chi Yuan} and Lin, {Cheng Yen} and Huang, {Chun Yao}",
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month = "3",
day = "1",
doi = "10.1016/j.trsl.2018.09.005",
language = "English",
volume = "205",
pages = "17--32",
journal = "Translational Research",
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T2 - a novel index for the prediction of HDL functionality

AU - Shih, Chun Ming

AU - Lin, Feng Yen

AU - Yeh, Jong Shiuan

AU - Lin, Yi Wen

AU - Loh, Shih Hurng

AU - Tsao, Nai Wen

AU - Nakagami, Hironori

AU - Morishita, Ryuichi

AU - Sawamura, Tatsuya

AU - Li, Chi Yuan

AU - Lin, Cheng Yen

AU - Huang, Chun Yao

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Lipid metabolic disorders play critical roles in atherogenesis. Traditionally, it has been suggested that reduced high density lipoprotein (HDL) levels might be an important morbidity indicator for cardiovascular diseases. Therefore, it has been argued that therapeutically raising HDL levels may reduce atherogenesis in patients with dyslipidemia. However, recent clinical trials to elevate serum HDL levels by pharmacologic approaches failed to demonstrate clinical efficacy. Thus, to investigate the functionality of HDL and to explore the possible clinical relevance as well as to define an effective indicator that can represent HDL function may provide another key and reference to disclose the clinical treatment of dyslipidemia. We analyzed the association between the data of dichlorofluorescein assay (assay the functionality of HDL), the effect of HDL on oxidized low density lipoprotein (oxLDL)-stimulated endothelial progenitor cells (EPCs) in vitro, levels of circulating EPCs, and ex vitro EPC colony forming units of each case, we defined the indicator (relative HDL index (RHDL index) = dichlorofluorescein assay result of each subject/dichlorofluorescein assay reading of our young healthy controls) that may represent functionality of HDL. HDL from healthy adults protected oxLDL-treated EPCs by modulating p38 mitogen-activated protein kinase and Rho activation and by promoting nitric oxide production. HDL from subject with RHDL index ≧2 also failed to restore the functionality of oxLDL-treated EPCs via cell-signaling pathways in vitro. The RHDL index significantly correlated with patients’ circulating EPC number or EPC colony forming units ex vivo. In conclusions, we explored the RHDL index as a score to predict a patient's EPC functions in vivo and ex vitro.

AB - Lipid metabolic disorders play critical roles in atherogenesis. Traditionally, it has been suggested that reduced high density lipoprotein (HDL) levels might be an important morbidity indicator for cardiovascular diseases. Therefore, it has been argued that therapeutically raising HDL levels may reduce atherogenesis in patients with dyslipidemia. However, recent clinical trials to elevate serum HDL levels by pharmacologic approaches failed to demonstrate clinical efficacy. Thus, to investigate the functionality of HDL and to explore the possible clinical relevance as well as to define an effective indicator that can represent HDL function may provide another key and reference to disclose the clinical treatment of dyslipidemia. We analyzed the association between the data of dichlorofluorescein assay (assay the functionality of HDL), the effect of HDL on oxidized low density lipoprotein (oxLDL)-stimulated endothelial progenitor cells (EPCs) in vitro, levels of circulating EPCs, and ex vitro EPC colony forming units of each case, we defined the indicator (relative HDL index (RHDL index) = dichlorofluorescein assay result of each subject/dichlorofluorescein assay reading of our young healthy controls) that may represent functionality of HDL. HDL from healthy adults protected oxLDL-treated EPCs by modulating p38 mitogen-activated protein kinase and Rho activation and by promoting nitric oxide production. HDL from subject with RHDL index ≧2 also failed to restore the functionality of oxLDL-treated EPCs via cell-signaling pathways in vitro. The RHDL index significantly correlated with patients’ circulating EPC number or EPC colony forming units ex vivo. In conclusions, we explored the RHDL index as a score to predict a patient's EPC functions in vivo and ex vitro.

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KW - ALT= alanine transaminase

KW - APOI = apocynin

KW - CAD = coronary artery disease

KW - CETP = cholesterol ester transfer protein

KW - DCFH-DA = 2′,7′-dichlorofluorescin diacetate

KW - HDL = high density lipoprotein

KW - HPODE = hydroperoxyoctadeca-9Z,11E-dienoic acid

KW - MNC = mononuclear cell

KW - NO = nitric oxide

KW - PAH-AH = platelet-activating factor acetylhydrolase

KW - PMA = phorbol 12-myristate 13-acetate

KW - PON1 = paraoxonase-1

KW - RHDL index = relative HDL index

KW - TBARS = thiobarbituric acid reactive substance

KW - TC = total cholesterol

KW - TG = triglycerides

KW - eNOS = endothelial nitric oxide synthase

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