Elsevier

Microvascular Research

Volume 82, Issue 2, September 2011, Pages 177-181
Microvascular Research

Regular Article
Endothelin-1 levels predict endothelial progenitor cell mobilization after acute myocardial infarction

https://doi.org/10.1016/j.mvr.2011.06.008Get rights and content

Abstract

Introduction

Endothelin-1 (ET-1), circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) are well-known modulators of endothelial function with important cardiac effects after an acute myocardial infarction. However, the relationship between them has never been assessed.

The objective of the present study was to establish the relationship between ET-1, CEC, and EPC concentrations after ST-elevation myocardial infarction (STEMI).

Methods

Endothelin-1, CEC, and EPC levels were measured in 61 patients presenting with a first STEMI. Samples were withdrawn acutely 6–24 h and 1 week after admission. Assessments included reperfusion outcomes (angiography), left ventricular ejection fraction (echocardiography), and 30-day mortality.

Results

Mean age was 60.6 ± 12.6 years and 45 (74%) were males. Higher ET-1 plasma levels were associated with lower EPC count after 1 week (7.45 ± 2.53 pg/ml if EPCs in the first quartile vs 5.72 ± 1.49 pg/ml if EPCs in the fourth quartile; P = 0.04).

In contrast with CEC and EPC count, higher ET-1 concentrations on admission were associated with Killip  2 (9.92 ± 2.01 pg/ml vs 7.32 ± 2.13 pg/ml; P < 0.001), post-reperfusion thrombolysis in myocardial infarction (TIMI) < 3 (8.65 ± 2.86 pg/ml vs 5.87 ± 1.93 pg/ml; P = 0.002), myocardial blush grade (MBG) < 3 (7.46 ± 2.48 pg/ml vs 5.99 ± 2.01 pg/ml; P = 0.004) and higher 30-day mortality (10.29 ± 2.02 pg/ml vs 6.57 ± 2.20 pg/ml; P = 0.005).

Conclusions

In STEMI patients, high ET-1 levels on admission predict a lower EPC mobilization after 1 week. Endothelin-1 provides better clinical, angiographic and echocardiographic information for prognosis than do CEC and EPC concentrations.

Graphical abstract

Highlights

► Relationship between ET-1, CEC and EPCs after myocardial infarction. ► Samples withdrawn acutely and 1 week after myocardial infarction onset. ► High ET-1 levels on admission predicted a lower EPC mobilization. ► ET-1 provides better prognostic information than do CEC and EPCs.

Introduction

Endothelial impairment is an independent predictor of acute cardiovascular events in patients with and without coronary artery disease (CAD) (Halcox et al., 2002). Endothelial dysfunction is also considered a predictor of left ventricular ejection fraction (LVEF) (Bae et al., 2004) associated with worse left ventricle remodeling after myocardial infarction (Matsuo et al., 2006).

Endothelin-1 (ET-1) is a well-known marker of endothelial dysfunction in patients with CAD (Iglarz and Clozel, 2007). In acute myocardial infarction (AMI), high ET-1 values on admission have been linked to poor angiographic outcomes after primary angioplasty (Eitel et al., 2010, Niccoli et al., 2006) and poor prognosis, including higher 30-day mortality (Khan et al., 2007, Yip et al., 2005).

The measurement of circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) also represents an important and novel technique for the assessment of endothelial injury and repair, respectively. Circulating endothelial cells are biomarkers of damage that correlate with several well-established markers of endothelial dysfunction and predict poor outcomes when elevated (Blann et al., 2005, Lee et al., 2005). In contrast, EPC are biomarkers of endothelial repair with potential cardioprotective effects. Low EPC levels after an AMI have been linked to poor outcomes, including worse LVEF and higher NT-proBNP concentrations (Wojakowski et al., 2006). The main mechanism of EPC mobilization from the bone marrow seems to depend on the activation of endothelial nitric oxide synthase (eNOS) in the presence of several mobilizing factors, such as vascular endothelial growth factor and placental growth factor (Li et al., 2006). Endothelin-1 decreases eNOS expression and could therefore play an important role in CEC and EPC mobilization (Sud and Black, 2009). However, no studies to date have assessed this potential interaction. The aim of the present study was to establish the relationship between ET-1 levels and CEC/EPC mobilization patterns in the early hours after an AMI.

Section snippets

Study population

Between June 2007 and January 2009, the study enrolled 61 nonconsecutive patients who underwent primary angioplasty for a first AMI with elevation of the segment ST in the electrocardiogram (STEMI). Inclusion criteria were prolonged chest pain (> 30 min) and ST-segment elevation > 1 mm in 2 or more adjacent leads within the first 12 h after onset of symptoms. Exclusion criteria were acute or chronic inflammatory disease, malignancy, or recent surgery, trauma, or infection. The study protocol was

Patient characteristics

The clinical characteristics of the study population are shown in Table 1. Mean symptoms-to-angioplasty time was 317 ± 255 min. The clinical and angiographic characteristics of the cohort are listed in Table 2. Suboptimal reperfusion was observed in 43.5% of patients. Three patients died within the first 30 days (2 of heart failure and 1 of cardiogenic shock). Mean peak CK-MB and troponin I after AMI were 182.8 ± 122.2 ng/ml and 178.65 ± 285.7 ng/ml, respectively. Left ventricular ejection fraction after

Discussion

The results of the present study suggest an association between high ET-1 levels on admission and low EPC mobilization after AMI. To our knowledge, this is the first study to assess the potential relationship between ET-1 and both CEC and EPC counts.

High ET-1 levels have been associated with poor angiographic (Niccoli et al., 2006) and clinical outcomes (Freixa et al., 2011, Yip et al., 2005). In agreement with previous studies (Niccoli et al., 2006, Yip et al., 2005), we found a significant

Limitations

There are several limitations to this study. First, although sample size is similar to previous studies, the number of patients is still relatively small and insufficient to establish the prognostic value of CEC/EPC mobilization for risk prediction in STEMI patients. Additionally, the small size of the sample led to a very low number of events that did not allow for a valid and stable multivariable analysis. Second, without serial ET-1, CEC and EPC measurements, we could not determine actual

Conclusions

In STEMI patients, high ET-1 levels on admission predict a lower EPC mobilization after 1 week. Endothelin-1 provides better clinical, angiographic and echocardiographic information for prognosis than do CEC and EPC concentrations.

Acknowledgments

Project funded by the Spanish Society of Cardiology, the Hospital Clinic of Barcelona and RD06/0009/1003 (Red HERACLES, Instituto de Salud Carlos III).

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