Proteomic analysis of endothelial cell secretome: A means of studying the pleiotropic effects of Hmg-CoA reductase inhibitors

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The clinical benefits of 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are closely related to their cholesterol-lowering properties. However, the inhibition of HMG-CoA reductase may also lead to pleiotropic effects due to the ability to inhibit the synthesis of non-steroidal isoprenoid compounds, thus exerting extra-beneficial effect in preventing atherosclerosis beyond their effect on the lipid profile. To identify new drug targets by means of which statins can promote some of their beneficial effects we used a global proteomic approach to analyse the secretome of endothelial cells, a major class of proteins that control a multitude of biological and physiological processes. Differentially expressed proteins were identified using a data-independent, label-free, mass spectrometry-based method. A total of 273 proteins were identified, including 112 that were differentially expressed: 29 uniquely expressed in control cells, 14 uniquely expressed in statin-treated cells, 51 down-regulated by statin, and 18 up-regulated by statin. Gene ontology analysis revealed modulated biological processes related to proteolysis, cellular component organisation and biogenesis, and response to stress. The findings were validated by biochemical assays, thus confirming the effectiveness of our proteomic approach. In conclusion, this study underlines the role of proteomics for the discovery of novel and unpredictable targets of statins.

Original languageEnglish
Pages (from-to)346-361
Number of pages16
JournalJournal of Proteomics
Volume78
DOIs
Publication statusPublished - Jan 14 2013

Fingerprint

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Endothelial cells
Coenzyme A
Proteomics
Oxidoreductases
Endothelial Cells
Biological Phenomena
Proteolysis
Physiological Phenomena
Gene Ontology
Proteins
Terpenes
Mass spectrometry
Ontology
Labels
Assays
Mass Spectrometry
Atherosclerosis
Genes
Cholesterol

Keywords

  • Atherosclerosis
  • Endothelium
  • Proteomics
  • Secretome
  • Statins

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

Cite this

@article{22445e4fbcce4112910313e95f0ce58f,
title = "Proteomic analysis of endothelial cell secretome: A means of studying the pleiotropic effects of Hmg-CoA reductase inhibitors",
abstract = "The clinical benefits of 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are closely related to their cholesterol-lowering properties. However, the inhibition of HMG-CoA reductase may also lead to pleiotropic effects due to the ability to inhibit the synthesis of non-steroidal isoprenoid compounds, thus exerting extra-beneficial effect in preventing atherosclerosis beyond their effect on the lipid profile. To identify new drug targets by means of which statins can promote some of their beneficial effects we used a global proteomic approach to analyse the secretome of endothelial cells, a major class of proteins that control a multitude of biological and physiological processes. Differentially expressed proteins were identified using a data-independent, label-free, mass spectrometry-based method. A total of 273 proteins were identified, including 112 that were differentially expressed: 29 uniquely expressed in control cells, 14 uniquely expressed in statin-treated cells, 51 down-regulated by statin, and 18 up-regulated by statin. Gene ontology analysis revealed modulated biological processes related to proteolysis, cellular component organisation and biogenesis, and response to stress. The findings were validated by biochemical assays, thus confirming the effectiveness of our proteomic approach. In conclusion, this study underlines the role of proteomics for the discovery of novel and unpredictable targets of statins.",
keywords = "Atherosclerosis, Endothelium, Proteomics, Secretome, Statins",
author = "Maura Brioschi and Sabrina Lento and Elena Tremoli and Cristina Banfi",
year = "2013",
month = "1",
day = "14",
doi = "10.1016/j.jprot.2012.10.003",
language = "English",
volume = "78",
pages = "346--361",
journal = "Journal of Proteomics",
issn = "1874-3919",
publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - Proteomic analysis of endothelial cell secretome

T2 - A means of studying the pleiotropic effects of Hmg-CoA reductase inhibitors

AU - Brioschi, Maura

AU - Lento, Sabrina

AU - Tremoli, Elena

AU - Banfi, Cristina

PY - 2013/1/14

Y1 - 2013/1/14

N2 - The clinical benefits of 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are closely related to their cholesterol-lowering properties. However, the inhibition of HMG-CoA reductase may also lead to pleiotropic effects due to the ability to inhibit the synthesis of non-steroidal isoprenoid compounds, thus exerting extra-beneficial effect in preventing atherosclerosis beyond their effect on the lipid profile. To identify new drug targets by means of which statins can promote some of their beneficial effects we used a global proteomic approach to analyse the secretome of endothelial cells, a major class of proteins that control a multitude of biological and physiological processes. Differentially expressed proteins were identified using a data-independent, label-free, mass spectrometry-based method. A total of 273 proteins were identified, including 112 that were differentially expressed: 29 uniquely expressed in control cells, 14 uniquely expressed in statin-treated cells, 51 down-regulated by statin, and 18 up-regulated by statin. Gene ontology analysis revealed modulated biological processes related to proteolysis, cellular component organisation and biogenesis, and response to stress. The findings were validated by biochemical assays, thus confirming the effectiveness of our proteomic approach. In conclusion, this study underlines the role of proteomics for the discovery of novel and unpredictable targets of statins.

AB - The clinical benefits of 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are closely related to their cholesterol-lowering properties. However, the inhibition of HMG-CoA reductase may also lead to pleiotropic effects due to the ability to inhibit the synthesis of non-steroidal isoprenoid compounds, thus exerting extra-beneficial effect in preventing atherosclerosis beyond their effect on the lipid profile. To identify new drug targets by means of which statins can promote some of their beneficial effects we used a global proteomic approach to analyse the secretome of endothelial cells, a major class of proteins that control a multitude of biological and physiological processes. Differentially expressed proteins were identified using a data-independent, label-free, mass spectrometry-based method. A total of 273 proteins were identified, including 112 that were differentially expressed: 29 uniquely expressed in control cells, 14 uniquely expressed in statin-treated cells, 51 down-regulated by statin, and 18 up-regulated by statin. Gene ontology analysis revealed modulated biological processes related to proteolysis, cellular component organisation and biogenesis, and response to stress. The findings were validated by biochemical assays, thus confirming the effectiveness of our proteomic approach. In conclusion, this study underlines the role of proteomics for the discovery of novel and unpredictable targets of statins.

KW - Atherosclerosis

KW - Endothelium

KW - Proteomics

KW - Secretome

KW - Statins

UR - http://www.scopus.com/inward/record.url?scp=84872684824&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872684824&partnerID=8YFLogxK

U2 - 10.1016/j.jprot.2012.10.003

DO - 10.1016/j.jprot.2012.10.003

M3 - Article

C2 - 23085226

AN - SCOPUS:84872684824

VL - 78

SP - 346

EP - 361

JO - Journal of Proteomics

JF - Journal of Proteomics

SN - 1874-3919

ER -