Effect of High Dose Statin Pretreatment on Endothelial Progenitor Cells After Percutaneous Coronary Intervention
A Eisen1, D Leshem-Lev, H Yavin
1Cardiology Department, Rabin Medical Center, 39 Jabotinsky St., 49100, Petah Tikva, Israel, a_alon1@netvision.net.il.
Insights
High-dose statins before PCI increase endothelial progenitor cells (EPCs) colony-forming units (CFUs). While initial levels are higher, EPC-CFUs remain similar post-PCI, suggesting a protective effect of statins on vascular repair.
Area of Science:
- Cardiology
- Vascular Biology
- Pharmacology
Background:
- High-dose statin pretreatment before percutaneous coronary intervention (PCI) reduces peri-procedural myocardial infarction.
- The precise mechanism behind these lipid-independent benefits remains unclear.
- Endothelial progenitor cells (EPCs) are crucial for vascular repair and re-endothelialization following injury.
Purpose of the Study:
- To investigate the impact of high-dose statins administered prior to PCI on the EPC profile.
- To test the hypothesis that statins limit PCI-induced endothelial injury and enhance re-endothelialization via EPC modulation.
Main Methods:
- A randomized study involving patients undergoing PCI, comparing high-dose atorvastatin with low-dose statins.
- EPC levels were assessed using flow cytometry (VEGFR-2+ CD133+, VEGFR-2+ CD34+) and colony-forming unit (CFU) assays before and 24 hours after PCI.
Main Results:
- Patients receiving high-dose atorvastatin showed significantly higher pre-PCI EPC-CFU counts compared to the low-dose group.
- Post-PCI, EPC-CFU counts were comparable between the high-dose and low-dose statin groups.
- No significant differences in flow cytometry analyses were observed between the groups.
Conclusions:
- High-dose atorvastatin pretreatment is associated with elevated EPC-CFU levels before PCI.
- A lower increment in EPC-CFUs post-PCI was observed in the high-dose atorvastatin group.
- These findings suggest a potential mechanism for the cardioprotective effects of statins, warranting further investigation.
Background:
Pretreatment with high-dose statins given before percutaneous coronary intervention (PCI) has been shown to have beneficial effects, in particular by reducing peri-procedural myocardial infarction. The mechanism of these lipid-independent beneficial statin effects is unclear. Circulating endothelial progenitor cells (EPCs) have an important role in the process of vascular repair, by promoting re-endothelization following injury. We hypothesized that statins can limit the extent of endothelial injury induced by PCI and promote re-endothelization by a positive effect on EPCs. We, therefore, aimed to examine the effect of high-dose statins given prior to PCI on EPCs profile.
Methods:
Included were patients, either statin naïve or treated chronically with low-dose statins, with stable or unstable angina who underwent PCI. Patients were randomized to receive either high-dose atorvastatin (80 mg the day before PCI and 40 mg 2-4 h before PCI) or low- dose statin. EPCs profile was examined before PCI and 24 h after it. Circulating EPCs levels were assessed by flow cytometry as the proportion of peripheral mononuclear cells co-expressing VEGFR-2+ CD133+ and VEGFR-2+ CD34+. The capacity of the cells to form colony forming units (CFUs) was quantified after 7 days of culture.
Results:
Twenty three patients (mean age 61.4 ± 7.4 years, 87.0% men) were included in the study, of which 12 received high-dose atorvastatin prior to PCI. The mean number of EPC-CFUs before PCI was higher in patients treated with high-dose atorvastatin vs. low-dose statins (165.8 ± 58.8 vs. 111.7 ± 38.2 CFUs/plate, respectively, p < 0.001). However, 24 h after the PCI, the number of EPC-CFUs was similar (188.0 ± 85.3 vs. 192.9 ± 66.5 CFUs/plate in patients treated with high-dose atorvastatin vs. low- dose statins, respectively, p = 0.15). There were no statistical significant differences in FACS analyses between the 2 groups.
Conclusions:
The current study showed higher EPC- CFUs levels in patients treated with high-dose atorvastatin before PCI and a lower increment in EPC-CFUs after PCI. These findings could account for the beneficial effects of statins given prior to PCI, yet further investigation is required.
