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Individual with subclinical atherosclerosis have impaired proliferation of blood outgrowth endothelial cells, which can be restored by statin therapy.

Martin-Ramirez J, Kok MG, Hofman M, Bierings R, Creemers EE, Meijers JC, Voorberg J, Pinto-Sietsma SJ - PLoS ONE (2014)

Bottom Line: We did not observe differences in the number of BOEC colonies and proliferation between premature CAD patients and FDRs.Unexpectedly, the number of BOEC colonies and BOEC proliferation were similar for premature CAD patients and healthy FDRs.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The Netherlands.

ABSTRACT

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.

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Colony formation curves of FDRs with subclinical atherosclerosis before and after statin treatment.This graph shows the median number of colonies at specific time points before and after statin therapy. Error bars indicate de inter quartile ranges. * P<0.05.
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pone-0099890-g002: Colony formation curves of FDRs with subclinical atherosclerosis before and after statin treatment.This graph shows the median number of colonies at specific time points before and after statin therapy. Error bars indicate de inter quartile ranges. * P<0.05.

Mentions: To study the effect of statin therapy on circulating BOEC precursors we analysed BOEC colony formation before and after statin therapy in ten subjects with severe subclinical atherosclerosis, as assessed by coronary CT-scanning. From day 14 on, we saw a significant increase in the number of BOEC colonies after statin therapy (figure 2). Not only the number of colonies at day 28 (0.04 [0–0.06] vs. 0.37 [0.13–0.85]; p<0.05), but also the maximum increase in colony number (0.04 [0–0.05] vs. 0.26 [0.07–0.59]; p<0.05) and the time to maximum increase (0.002 [0–0.003] vs. 0.013 [0.005–0.034]; p<0.05) were significantly increased after statin therapy. Also, the proliferative capacity was increased after statin therapy (30% vs 80%, table 4), but due to small sample size, this did not reach statistical significance.


Individual with subclinical atherosclerosis have impaired proliferation of blood outgrowth endothelial cells, which can be restored by statin therapy.

Martin-Ramirez J, Kok MG, Hofman M, Bierings R, Creemers EE, Meijers JC, Voorberg J, Pinto-Sietsma SJ - PLoS ONE (2014)

Colony formation curves of FDRs with subclinical atherosclerosis before and after statin treatment.This graph shows the median number of colonies at specific time points before and after statin therapy. Error bars indicate de inter quartile ranges. * P<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4067291&req=5

pone-0099890-g002: Colony formation curves of FDRs with subclinical atherosclerosis before and after statin treatment.This graph shows the median number of colonies at specific time points before and after statin therapy. Error bars indicate de inter quartile ranges. * P<0.05.
Mentions: To study the effect of statin therapy on circulating BOEC precursors we analysed BOEC colony formation before and after statin therapy in ten subjects with severe subclinical atherosclerosis, as assessed by coronary CT-scanning. From day 14 on, we saw a significant increase in the number of BOEC colonies after statin therapy (figure 2). Not only the number of colonies at day 28 (0.04 [0–0.06] vs. 0.37 [0.13–0.85]; p<0.05), but also the maximum increase in colony number (0.04 [0–0.05] vs. 0.26 [0.07–0.59]; p<0.05) and the time to maximum increase (0.002 [0–0.003] vs. 0.013 [0.005–0.034]; p<0.05) were significantly increased after statin therapy. Also, the proliferative capacity was increased after statin therapy (30% vs 80%, table 4), but due to small sample size, this did not reach statistical significance.

Bottom Line: We did not observe differences in the number of BOEC colonies and proliferation between premature CAD patients and FDRs.Unexpectedly, the number of BOEC colonies and BOEC proliferation were similar for premature CAD patients and healthy FDRs.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The Netherlands.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus