Individual with Subclinical Atherosclerosis Have Impaired Proliferation of Blood Outgrowth Endothelial Cells, Which Can Be Restored by Statin Therapy

To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of patients with premature CAD and their first degree relatives (FDR). Additionally we evaluated the influence of statin treatment on circulatin...

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Vydáno v:PloS one Ročník 9; číslo 6; s. e99890
Hlavní autoři: Martin-Ramirez, Javier, Kok, Maayke G. M., Hofman, Menno, Bierings, Ruben, Creemers, Esther E., Meijers, Joost C. M., Voorberg, Jan, Pinto-Sietsma, Sara-Joan
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 23.06.2014
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ISSN:1932-6203, 1932-6203
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Abstract To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of patients with premature CAD and their first degree relatives (FDR). Additionally we evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis. Patients with premature CAD (men <51 yr, women <56 yr) and their FDRs were included. Based on coronary calcification (CAC) scores FDRs were divided in a group of healthy subjects (CAC = 0) and subjects with subclinical atherosclerosis (CAC>0). We did not observe differences in the number of BOEC colonies and proliferation between premature CAD patients and FDRs. FDRs with subclinical atherosclerosis had lower colony numbers compared with healthy FDRs, however this was not statistically significant, and BOEC proliferation was significantly impaired (OR = 0.45, 95% CI 0.21-0.96). Unexpectedly, the number of BOEC colonies and BOEC proliferation were similar for premature CAD patients and healthy FDRs. Since a considerable number of premature CAD patients used statins, we studied the number of BOEC precursors as well as their proliferative capacity in ten individuals with subclinical atherosclerosis, before and after statin therapy. Interestingly, FDRs with subclinical atherosclerosis showed a significant increase in the number of BOEC colonies after statin therapy. BOEC proliferation of subjects with subclinical atherosclerosis is impaired compared with healthy controls. In these subjects, statin therapy significantly increased the number of circulating BOEC precursors as well as their proliferative capacity, revealing a beneficial effect of statins on endothelial regeneration.
AbstractList To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of patients with premature CAD and their first degree relatives (FDR). Additionally we evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis. Patients with premature CAD (men <51 yr, women <56 yr) and their FDRs were included. Based on coronary calcification (CAC) scores FDRs were divided in a group of healthy subjects (CAC = 0) and subjects with subclinical atherosclerosis (CAC>0). We did not observe differences in the number of BOEC colonies and proliferation between premature CAD patients and FDRs. FDRs with subclinical atherosclerosis had lower colony numbers compared with healthy FDRs, however this was not statistically significant, and BOEC proliferation was significantly impaired (OR = 0.45, 95% CI 0.21-0.96). Unexpectedly, the number of BOEC colonies and BOEC proliferation were similar for premature CAD patients and healthy FDRs. Since a considerable number of premature CAD patients used statins, we studied the number of BOEC precursors as well as their proliferative capacity in ten individuals with subclinical atherosclerosis, before and after statin therapy. Interestingly, FDRs with subclinical atherosclerosis showed a significant increase in the number of BOEC colonies after statin therapy. BOEC proliferation of subjects with subclinical atherosclerosis is impaired compared with healthy controls. In these subjects, statin therapy significantly increased the number of circulating BOEC precursors as well as their proliferative capacity, revealing a beneficial effect of statins on endothelial regeneration.
Background To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of patients with premature CAD and their first degree relatives (FDR). Additionally we evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis. Methods and Results Patients with premature CAD (men <51 yr, women <56 yr) and their FDRs were included. Based on coronary calcification (CAC) scores FDRs were divided in a group of healthy subjects (CAC = 0) and subjects with subclinical atherosclerosis (CAC>0). We did not observe differences in the number of BOEC colonies and proliferation between premature CAD patients and FDRs. FDRs with subclinical atherosclerosis had lower colony numbers compared with healthy FDRs, however this was not statistically significant, and BOEC proliferation was significantly impaired (OR = 0.45, 95% CI 0.21–0.96). Unexpectedly, the number of BOEC colonies and BOEC proliferation were similar for premature CAD patients and healthy FDRs. Since a considerable number of premature CAD patients used statins, we studied the number of BOEC precursors as well as their proliferative capacity in ten individuals with subclinical atherosclerosis, before and after statin therapy. Interestingly, FDRs with subclinical atherosclerosis showed a significant increase in the number of BOEC colonies after statin therapy. Conclusion BOEC proliferation of subjects with subclinical atherosclerosis is impaired compared with healthy controls. In these subjects, statin therapy significantly increased the number of circulating BOEC precursors as well as their proliferative capacity, revealing a beneficial effect of statins on endothelial regeneration.
To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of patients with premature CAD and their first degree relatives (FDR). Additionally we evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis.BACKGROUNDTo study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of patients with premature CAD and their first degree relatives (FDR). Additionally we evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis.Patients with premature CAD (men <51 yr, women <56 yr) and their FDRs were included. Based on coronary calcification (CAC) scores FDRs were divided in a group of healthy subjects (CAC = 0) and subjects with subclinical atherosclerosis (CAC>0). We did not observe differences in the number of BOEC colonies and proliferation between premature CAD patients and FDRs. FDRs with subclinical atherosclerosis had lower colony numbers compared with healthy FDRs, however this was not statistically significant, and BOEC proliferation was significantly impaired (OR = 0.45, 95% CI 0.21-0.96). Unexpectedly, the number of BOEC colonies and BOEC proliferation were similar for premature CAD patients and healthy FDRs. Since a considerable number of premature CAD patients used statins, we studied the number of BOEC precursors as well as their proliferative capacity in ten individuals with subclinical atherosclerosis, before and after statin therapy. Interestingly, FDRs with subclinical atherosclerosis showed a significant increase in the number of BOEC colonies after statin therapy.METHODS AND RESULTSPatients with premature CAD (men <51 yr, women <56 yr) and their FDRs were included. Based on coronary calcification (CAC) scores FDRs were divided in a group of healthy subjects (CAC = 0) and subjects with subclinical atherosclerosis (CAC>0). We did not observe differences in the number of BOEC colonies and proliferation between premature CAD patients and FDRs. FDRs with subclinical atherosclerosis had lower colony numbers compared with healthy FDRs, however this was not statistically significant, and BOEC proliferation was significantly impaired (OR = 0.45, 95% CI 0.21-0.96). Unexpectedly, the number of BOEC colonies and BOEC proliferation were similar for premature CAD patients and healthy FDRs. Since a considerable number of premature CAD patients used statins, we studied the number of BOEC precursors as well as their proliferative capacity in ten individuals with subclinical atherosclerosis, before and after statin therapy. Interestingly, FDRs with subclinical atherosclerosis showed a significant increase in the number of BOEC colonies after statin therapy.BOEC proliferation of subjects with subclinical atherosclerosis is impaired compared with healthy controls. In these subjects, statin therapy significantly increased the number of circulating BOEC precursors as well as their proliferative capacity, revealing a beneficial effect of statins on endothelial regeneration.CONCLUSIONBOEC proliferation of subjects with subclinical atherosclerosis is impaired compared with healthy controls. In these subjects, statin therapy significantly increased the number of circulating BOEC precursors as well as their proliferative capacity, revealing a beneficial effect of statins on endothelial regeneration.
To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of patients with premature CAD and their first degree relatives (FDR). Additionally we evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis. BOEC proliferation of subjects with subclinical atherosclerosis is impaired compared with healthy controls. In these subjects, statin therapy significantly increased the number of circulating BOEC precursors as well as their proliferative capacity, revealing a beneficial effect of statins on endothelial regeneration.
BackgroundTo study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of patients with premature CAD and their first degree relatives (FDR). Additionally we evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis.Methods and resultsPatients with premature CAD (men <51 yr, women <56 yr) and their FDRs were included. Based on coronary calcification (CAC) scores FDRs were divided in a group of healthy subjects (CAC = 0) and subjects with subclinical atherosclerosis (CAC>0). We did not observe differences in the number of BOEC colonies and proliferation between premature CAD patients and FDRs. FDRs with subclinical atherosclerosis had lower colony numbers compared with healthy FDRs, however this was not statistically significant, and BOEC proliferation was significantly impaired (OR = 0.45, 95% CI 0.21-0.96). Unexpectedly, the number of BOEC colonies and BOEC proliferation were similar for premature CAD patients and healthy FDRs. Since a considerable number of premature CAD patients used statins, we studied the number of BOEC precursors as well as their proliferative capacity in ten individuals with subclinical atherosclerosis, before and after statin therapy. Interestingly, FDRs with subclinical atherosclerosis showed a significant increase in the number of BOEC colonies after statin therapy.ConclusionBOEC proliferation of subjects with subclinical atherosclerosis is impaired compared with healthy controls. In these subjects, statin therapy significantly increased the number of circulating BOEC precursors as well as their proliferative capacity, revealing a beneficial effect of statins on endothelial regeneration.
Background To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of patients with premature CAD and their first degree relatives (FDR). Additionally we evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis. Methods and Results Patients with premature CAD (men <51 yr, women <56 yr) and their FDRs were included. Based on coronary calcification (CAC) scores FDRs were divided in a group of healthy subjects (CAC = 0) and subjects with subclinical atherosclerosis (CAC>0). We did not observe differences in the number of BOEC colonies and proliferation between premature CAD patients and FDRs. FDRs with subclinical atherosclerosis had lower colony numbers compared with healthy FDRs, however this was not statistically significant, and BOEC proliferation was significantly impaired (OR = 0.45, 95% CI 0.21–0.96). Unexpectedly, the number of BOEC colonies and BOEC proliferation were similar for premature CAD patients and healthy FDRs. Since a considerable number of premature CAD patients used statins, we studied the number of BOEC precursors as well as their proliferative capacity in ten individuals with subclinical atherosclerosis, before and after statin therapy. Interestingly, FDRs with subclinical atherosclerosis showed a significant increase in the number of BOEC colonies after statin therapy. Conclusion BOEC proliferation of subjects with subclinical atherosclerosis is impaired compared with healthy controls. In these subjects, statin therapy significantly increased the number of circulating BOEC precursors as well as their proliferative capacity, revealing a beneficial effect of statins on endothelial regeneration.
Background To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of patients with premature CAD and their first degree relatives (FDR). Additionally we evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis. Methods and Results Patients with premature CAD (men <51 yr, women 0). We did not observe differences in the number of BOEC colonies and proliferation between premature CAD patients and FDRs. FDRs with subclinical atherosclerosis had lower colony numbers compared with healthy FDRs, however this was not statistically significant, and BOEC proliferation was significantly impaired (OR = 0.45, 95% CI 0.21-0.96). Unexpectedly, the number of BOEC colonies and BOEC proliferation were similar for premature CAD patients and healthy FDRs. Since a considerable number of premature CAD patients used statins, we studied the number of BOEC precursors as well as their proliferative capacity in ten individuals with subclinical atherosclerosis, before and after statin therapy. Interestingly, FDRs with subclinical atherosclerosis showed a significant increase in the number of BOEC colonies after statin therapy. Conclusion BOEC proliferation of subjects with subclinical atherosclerosis is impaired compared with healthy controls. In these subjects, statin therapy significantly increased the number of circulating BOEC precursors as well as their proliferative capacity, revealing a beneficial effect of statins on endothelial regeneration.
Audience Academic
Author Martin-Ramirez, Javier
Pinto-Sietsma, Sara-Joan
Hofman, Menno
Bierings, Ruben
Creemers, Esther E.
Voorberg, Jan
Meijers, Joost C. M.
Kok, Maayke G. M.
AuthorAffiliation European Institute of Oncology, Italy
5 Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands
3 The Heart Failure Research Center, Academic Medical Center, Amsterdam, The Netherlands
1 Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The Netherlands
4 Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
2 Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
AuthorAffiliation_xml – name: 5 Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands
– name: 3 The Heart Failure Research Center, Academic Medical Center, Amsterdam, The Netherlands
– name: 1 Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The Netherlands
– name: 4 Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
– name: 2 Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
– name: European Institute of Oncology, Italy
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  givenname: Javier
  surname: Martin-Ramirez
  fullname: Martin-Ramirez, Javier
– sequence: 2
  givenname: Maayke G. M.
  surname: Kok
  fullname: Kok, Maayke G. M.
– sequence: 3
  givenname: Menno
  surname: Hofman
  fullname: Hofman, Menno
– sequence: 4
  givenname: Ruben
  surname: Bierings
  fullname: Bierings, Ruben
– sequence: 5
  givenname: Esther E.
  surname: Creemers
  fullname: Creemers, Esther E.
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  givenname: Joost C. M.
  surname: Meijers
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  surname: Voorberg
  fullname: Voorberg, Jan
– sequence: 8
  givenname: Sara-Joan
  surname: Pinto-Sietsma
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/24955753$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
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DocumentTitleAlternate Subclinical Atherosclerosis Is Related to Impaired BOECs Proliferation
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Competing Interests: The authors have declared that no competing interest exist.
Conceived and designed the experiments: MK EC JM JV SJP. Performed the experiments: JMR MK MH. Analyzed the data: MK SJP. Contributed reagents/materials/analysis tools: JMR MH. Wrote the paper: JMR MK JV SJP. Imaging of the BOECs: RB.
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Snippet To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of...
Background To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells...
BackgroundTo study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells...
Background To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells...
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StartPage e99890
SubjectTerms Adult
Aged
Arteriosclerosis
Atherosclerosis
Atherosclerosis - drug therapy
Atherosclerosis - metabolism
Atherosclerosis - pathology
Biology and Life Sciences
Blood
Blood pressure
Calcification
Calcification (ectopic)
Cardiovascular agents
Cardiovascular disease
Cell proliferation
Cell Proliferation - drug effects
Cholesterol
Colonies
Comparative analysis
Coronary artery
Coronary artery disease
Coronary heart disease
Coronary vessels
Endothelial cells
Endothelial Cells - metabolism
Endothelial Cells - pathology
Endothelium
Family medical history
Female
Health risk assessment
Heart attacks
Heart diseases
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage
Laboratories
Male
Medical imaging
Medicine
Medicine and Health Sciences
Middle Aged
Patients
Plasma
Proteins
Regeneration
Statins
Statistical analysis
Stem Cells - metabolism
Stem Cells - pathology
Studies
Therapy
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Title Individual with Subclinical Atherosclerosis Have Impaired Proliferation of Blood Outgrowth Endothelial Cells, Which Can Be Restored by Statin Therapy
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