Effect of High Dose Statin Pretreatment on Endothelial Progenitor Cells After Percutaneous Coronary Intervention (HIPOCRATES Study)

Eisen, Alon; Leshem-Lev, Dorit; Yavin, Hagai; Orvin, Katia; Mager, Aviv; Rechavia, Eldad; Bental, Tamir; Dadush, Oshrat; Battler, Alexander; Kornowski, Ran; Lev, Eli I.

doi:10.1007/s10557-015-6575-8

Cited by 17 publications

(11 citation statements)

References 21 publications

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“…Earlier statin administration was found to be significantly correlated with a lower risk of AMI, MACEs and major adverse cardiac and cerebrovascular events within 30 days after treatment (12). Previous observational studies of patients after STEMI have suggested that previous chronic statin use may improve coronary blood flow and is associated with reduced short-term mortality (13). Based on the findings of these studies, it may be hypothesized that long-term statin use prior to PPCI could improve the treatment outcomes of patients after AMI.…”

Section: Introductionmentioning

confidence: 99%

Long-term statin use before primary percutaneous coronary intervention improves treatment outcomes of acute myocardial infarction

Guo¹,

Yang²,

Mu³

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Numerous studies have reported that high-dose statin loading therapy prior to primary percutaneous coronary intervention (PPCI) improves the clinical outcomes of patients following acute myocardial infarction (AMI). However, little is known about the effects of long-term statin use prior to PPCI on such outcomes. Therefore, the aim of the present analysis was to clarify the effects of long-term statin use before PPCI on the treatment outcomes of patients following AMI. The records of 213 patients who had AMI and met the inclusion criteria were retrospectively reviewed. Patients were divided into two groups: A control group (n=178) who had received no statin pretreatment before AMI onset, and a statin group (n=35) who had received statin treatment for ≥1 month before AMI onset. All patients received a standard treatment regimen for the secondary prevention of coronary artery disease after PPCI. Baseline clinical variables, details of the PPCI procedure and clinical outcomes within 3 months after treatment were reviewed. Patients in the statin group were significantly older than those in the control group (P=0.003). Compared with the control group, there was a greater proportion of patients with hyperlipidemia and previous angina pectoris in the statin group. There were no differences in the use of other drugs (aspirin, β-blockers and angiotensin-converting enzyme inhibitors) prior to PPCI between the two groups. The corrected TIMI frame count (cTFC) was significantly lower in the statin group than in the control group (24.1±12.8 vs. 29.4±14.3, respectively; P=0.043). Multivariable linear regression analysis showed that long-term statin use before AMI was a significant predictor of cTFC after PPCI (P=0.012).Furthermore, the incidence of major adverse cardiac events within 3 months after PPCI was higher in the control group than in the statin group (16.8 vs. 2.9%, respectively; P=0.032). Logistic regression analysis showed that previous statin use was associated with the incidence of major adverse cardiac events within 3 months after treatment (P=0.012). The results of the present study demonstrate that long-term statin use prior to PPCI improved treatment outcomes after AMI in actual clinical practice.

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Section: Introductionmentioning

confidence: 99%

Long-term statin use before primary percutaneous coronary intervention improves treatment outcomes of acute myocardial infarction

Guo¹,

Yang²,

Mu³

et al. 2017

Experimental and Therapeutic Medicine

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“…High doses of atorvastatin have been reported to exert beneficial effects in cardiovascular disease in clinical practice. For instance, high doses facilitated EPC mobilization in patients that had undergone percutaneous coronary intervention, which may limit the extent of endothelial injury (6,7). In addition, a high dose of atorvastatin was revealed to prevent contrast-induced nephropathy following carotid artery stenting (8).…”

Section: Introductionmentioning

confidence: 99%

Effects of various doses of atorvastatin on vascular endothelial cell apoptosis and autophagy in�vitro

Zhao

Chang

et al. 2019

Mol Med Report

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Atorvastatin (Lipitor™) is a lipid-lowering agent that is widely used in the treatment of cardiovascular diseases. Previous research has largely focused on its cholesterol-lowering effects; however, a limited number of studies have investigated the actions of atorvastatin on vascular endothelial cells. In the present study, the effects of various doses of atorvastatin were investigated on human umbilical vein endothelial cells (HUVECs). HUVECs were treated with various concentrations of atorvastatin in serum-free or serum-containing medium, and alterations in HUVEC morphology were observed. Cell survival and necrosis rates were evaluated using sulforhodamine B and lactate dehydrogenase assays, respectively. In addition, the protein expression levels of cellular apoptosis and autophagy markers were detected using western blot analysis. The results revealed that HUVEC morphology was altered following treatment with various concentrations of atorvastatin. In addition, autophagy was demonstrated to be induced by atorvastatin treatment at all concentrations, whereas high concentrations appeared to induce apoptosis and suppress the survival of HUVECs. In conclusion, the results of the present study suggested that various doses of atorvastatin may exert differential effects on HUVECs, and high doses may suppress angiogenesis. Therefore, atorvastatin may present a novel potential anti-tumor therapeutic strategy. However, further studies are required to fully elucidate the association between the dose of atorvastatin and its clinical outcome.

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“…They have cardioprotective effects independent of their lipid-lowering function that includes improving the biological function of EPC 5 . However, these pleiotropic effects require long-term administration of high statin dosages 6 , 7 , which is limited by relatively low oral bioavailability and therefore lead to an increased risk of adverse reactions 8 , 9 .…”

Section: Introductionmentioning

confidence: 99%

Pitavastatin nanoparticle-engineered endothelial progenitor cells repair injured vessels

Liu

Bao

et al. 2017

Sci Rep

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Endothelial progenitor cells (EPC) participate in vessel recovery and maintenance of normal endothelial function. Therefore, pitavastatin-nanoparticles (NPs)-engineered EPC may be effective in repairing injured vasculature. Pitavastatin-loaded poly(lactic-co-glycolic) acid (PLGA) NPs were obtained via ultrasonic emulsion solvent evaporation with PLGA as the carrier encapsulating pitavastatin. The effects and mechanism of pitavastatin-NPs on EPC proliferation in vitro were evaluated. Then, EPC that internalized pitavastatin-NPs were transplanted into rats after carotid artery injury. EPC homing, re-endothelialization, and neointima were evaluated by fluorescence labeling, evans Blue and hematoxylin/eosin (H&E) staining. Pitavastatin-NPs significantly improved EPC proliferation compared with control and pitavastatin group. Those effects were blocked by pretreatment with the pharmacological phosphoinositide 3-kinase (PI3K) blockers LY294002. After carotid artery injury, more transplanted EPC were detected in target zone in Pitavastatin-NPs group than pitavastatin and control group. Re-endothelialization was promoted and intimal hyperplasia was inhibited as well. Thus, pitavastatin-NPs promote EPC proliferation via PI3K signaling and accelerate recovery of injured carotid artery.

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Effect of High Dose Statin Pretreatment on Endothelial Progenitor Cells After Percutaneous Coronary Intervention (HIPOCRATES Study)

Abstract: 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.

Cited by 17 publications

References 21 publications

Long-term statin use before primary percutaneous coronary intervention improves treatment outcomes of acute myocardial infarction

Long-term statin use before primary percutaneous coronary intervention improves treatment outcomes of acute myocardial infarction

Effects of various doses of atorvastatin on vascular endothelial cell apoptosis and autophagy in�vitro

Pitavastatin nanoparticle-engineered endothelial progenitor cells repair injured vessels

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