Endothelial Progenitor Cells, Microvascular Obstruction, and Left Ventricular Remodeling in Patients With ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

doi:10.1016/j.amjcard.2013.04.056

The American Journal of Cardiology

Volume 112, Issue 6, 15 September 2013, Pages 782-791

https://doi.org/10.1016/j.amjcard.2013.04.056 Get rights and content

Endothelial progenitor cells (EPCs) are released from the bone marrow during cardiac ischemic events, potentially influencing vascular and myocardial repair. We assessed the clinical and angiographic correlates of EPC mobilization at the time of primary percutaneous coronary intervention in 78 patients with ST elevation myocardial infarction and the impact of both baseline and follow-up EPC levels on left ventricular (LV) remodeling. Blood samples were drawn from the aorta and the culprit coronary artery for cytofluorimetric EPC detection (CD34+CD45dimKDR+ cells, in percentage of cytofluorimetric counts). Area at risk was assessed by Bypass Angioplasty Revascularization Investigation myocardial jeopardy index, thrombotic burden as thrombus score and microvascular obstruction (MVO) as a combination of ST segment resolution and myocardial blush grade. Echocardiographic evaluation of LV remodeling was performed at 1-year follow-up in 54 patients, whereas peripheral EPC levels were reassessed in 40 patients. EPC levels during primary percutaneous coronary intervention were significantly higher in intracoronary than in aortic blood (0.043% vs 0.0006%, p <0.001). Both intracoronary and aortic EPC were related to area at risk extent, to intracoronary thrombus score (p <0.001), and inversely to MVO (p = 0.001). Peripheral EPC levels at 1-year follow-up were lower in patients with LV remodeling than in those without (0.001% [0.001 to 0.002] vs 0.003% [0.002 to 0.010]; p = 0.01) and independently predicted absence of remodeling at multivariate analysis. In conclusion, a rapid intracoronary EPC recruitment takes place in the early phases of ST elevation myocardial infarction, possibly reflecting an attempted reparative response. The extent of this mobilization seems to be correlated to the area at risk and to the amount of MVO. Persistently low levels of EPC are associated to LV remodeling.

Section snippets

Methods

Seventy-eight consecutive patients with ST elevation myocardial infarction, treated with primary PCI with thrombus aspiration were prospectively enrolled from 170 primary PCIs performed in our institution during August 2009 to December 2010 (Supplementary Figure 1). All patients were admitted to our coronary care unit with chest pain, new persistent ST segment elevation, high-sensitivity cardiac Troponin T >0.0015 ng/ml, and/or new regional wall motion abnormalities.⁹ Exclusion criteria for all

Results

Clinical and angiographic characteristics of enrolled patients are listed in Table 1, Table 2, respectively.

EPC levels (percentage of cytofluorimetric events) were significantly higher in intracoronary than in aortic blood (0.043% [0.004 to 0.154] vs 0.006% [0.001 to 0.083], p <0.001; Figure 1). In contrast, intracoronary and aortic blood did not differ with regard to hematocrit (42.0% [31.5 to 43.8] vs 39.1% [33.5 to 41], p = 0.7) and total white blood cell count (11,260 n/μl [10,507 to

Discussion

In the present study, we demonstrate that, in patients with ST elevation myocardial infarction, CD34+CD45dimKDR+ progenitor cell levels, defined as EPC according to the recently modified International Society of Hematotherapy and Graft Engineering (ISHAGE) protocol,¹⁹ are significantly higher in blood samples collected from the infarct-related artery than in samples collected from the ascending aorta. Intracoronary and aortic EPC levels were related to the extension of angiographically assessed

Acknowledgment

The authors would like to thank all the members of the Coronary Care Unit and Catheterization Laboratory of the “Policlinico A. Gemelli.”

References (30)

M. Massa et al.
Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction
Blood
(2005)
I. Porto et al.
Are endothelial progenitor cells mobilized by myocardial ischemia or myocardial necrosis? A cardiac magnetic resonance study
Atherosclerosis
(2011)
S.C. Bekkers et al.
Microvascular obstruction: underlying pathophysiology and clinical diagnosis
J Am Coll Cardiol
(2010)
I. Porto et al.
Angiographic assessment of microvascular perfusion–myocardial blush in clinical practice
Am Heart J
(2010)
I. Porto et al.
Quantitative blush evaluator accurately quantifies microvascular dysfunction in patients with ST-elevation myocardial infarction: comparison with cardiovascular magnetic resonance
Am Heart J
(2011)
F. Burzotta et al.
Manual thrombus-aspiration improves myocardial reperfusion: the Randomized Evaluation of the Effect of Mechanical Reduction of Distal Embolization by Thrombus-Aspiration in Primary and Rescue Angioplasty (REMEDIA) trial
J Am Coll Cardiol
(2005)
G. Niccoli et al.
Myocardial no-reflow in humans
J Am Coll Cardiol
(2009)
L. Bolognese et al.
Early predictors of left ventricular remodeling after acute myocardial infarction
Am Heart J
(1999)
C. Dubois et al.
Differential effects of progenitor cell populations on left ventricular remodeling and myocardial neovascularization after myocardial infarction
J Am Coll Cardiol
(2010)
A.M. Leone et al.
Effect of intensive vs standard statin therapy on endothelial progenitor cells and left ventricular function in patients with acute myocardial infarction: statins for regeneration after acute myocardial infarction and PCI (STRAP) trial
Int J Cardiol
(2008)

L. Galiuto et al.

The extent of microvascular damage during myocardial contrast echocardiography is superior to other known indexes of post-infarct reperfusion in predicting left ventricular remodeling: results of the multicenter AMICI study

J Am Coll Cardiol

(2008)

A.M. Leone et al.

From bone marrow to the arterial wall: the ongoing tale of endothelial progenitor cells

Eur Heart J

(2009)

A.M. Leone et al.

Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function

Eur Heart J

(2005)

R. Wyderka et al.

Mobilization of CD34+CXCR4+ stem/progenitor cells and the parameters of left ventricular function and remodeling in 1-year follow-up of patients with acute myocardial infarction

Mediators Inflamm

(2012)

W. Wojakowski et al.

Mobilization of CD34(+), CD117(+), CXCR4(+), c-met(+) stem cells is correlated with left ventricular ejection fraction and plasma NT-proBNP levels in patients with acute myocardial infarction

Eur Heart J

(2006)

Cited by (12)

Imbalance between the circulating endothelium-derived apoptotic microparticles and the endothelial colony-forming units of progenitor cells in patients undergoing diagnostic coronary angiography
2021, Advances in Medical Sciences
Citation Excerpt :
Circulating EPCs play an important role in endothelial repair and regeneration [35]. The presence of colony-forming units of EPCs or high circulating levels of these progenitor cells is associated with reduced microvascular obstruction after AMI, leading to lower left ventricular remodeling [36,37]. Conversely, an inverse correlation between EPCs and several risk factors for CAD has been described [12,19,38,39].
The involvement of the circulating endothelium-derived microparticles (EMPs) and the endothelial progenitor cells (EPCs) has been shown in the pathogenesis of coronary artery disease (CAD). The current study aimed to explore whether the Friesinger index is associated with the levels of the apoptotic CD144+/CD31+/annexin V+ EMPs and the number of endothelial colony-forming units of progenitor cells in patients undergoing coronary angiography.
Fifty-seven patients with a median age of 62 years (range: 48–84 years) were enrolled. Quantification of the apoptotic CD144⁺/CD31⁺/annexin V⁺ EMPs was performed by flow cytometry. The number of endothelial colony-forming units defined by CFU-Hill was assessed by cell culture.
There was a positive correlation between the Friesinger index and the circulating levels of the apoptotic CD144⁺/CD31⁺/annexin V⁺ EMPs (rho=0.817, p<0.001), whereas a negative correlation was found with the number of CFU-Hill (rho = − 0.649, p<0.001). Multivariable logistic analysis showed that the risk of having moderate/severe CAD was five times greater among male patients (OR:5.32; 95% CI: 1.19 - 16.33; p=0.038) and almost one and a half times higher among those with a higher level of apoptotic CD144⁺/CD31⁺/annexin V⁺ EMPs (OR:1.74; 95% CI: 1.23 - 2.28; p=0.001). Finally, the circulating levels of apoptotic EMPs labelled for CD144⁺/CD31⁺/annexin V⁺ presented a good discrimination of moderate/severe CAD, with an AUC of 0.85 (95% CI = 0.74 - 0.96; p< 0.001).
Moderate or severe CAD is associated with increased levels of apoptotic EMPs and reduced EPC colony-forming capacity, increasing the occurrence of endothelial injuries.
Dual role of circulating endothelial progenitor cells in stent struts endothelialisation and neointimal regrowth: A substudy of the IN-PACT CORO trial
2015, Cardiovascular Revascularization Medicine
Citation Excerpt :
Initial evidence from our group, however, support the potential application of at least one type of DCB to a subset of de novo lesions [10]. Endothelial progenitor cells (EPCs) are bone marrow derived elements with homeostatic and reparative properties [11], increased in the blood of patients with acute ST elevation myocardial infarction and linked to reduced left ventricular remodelling [12]. EPCs have also been controversially invoked to explain stent endothelialisation, as the regeneration of endothelium is considered to involve either EPC homing from blood flow at the site of injury, or endothelium regrowth from both sides of the stented part of the vessel [13].
Endothelialisation is a crucial event after percutaneous coronary intervention (PCI). Endothelial progenitor cells (EPCs) are bone marrow derived elements with reparative properties. We aimed to assess the relationship between circulating EPC levels and stent neointimal hyperplasia (NIH) using frequency domain optical coherence tomography (FD-OCT).
Patients undergoing elective PCI to native vessels and randomised to bare metal stent (BMS) alone versus BMS plus drug coated balloon (DCB) were included. At six months, angiographic follow-up and FD-OCT were performed to measure percentage neointimal hyperplasia volume obstruction (%NIHV), and percentage of uncovered stent struts (%US). Venous blood samples were obtained before the procedure and at six months to detect CD34+CD45dimKDR + EPC levels.
Twenty patients were enrolled. A significant relationship was observed between baseline EPC levels and %NIHV (R: 0.63, p: 0.03) and %US (R: − 0.56, p: 0.01) at follow-up. Both EPC levels and DCB use were independently related to %NIHV (β: 0.55; p < 0.001 and β: − 0.51; p: 0.001, respectively), while only EPC levels were independently associated to %US (β: − 0.52; p: 0.01). Higher %NIHV (p: 0.004) and lower %US (p: 0.005) were observed in patients with stable or increasing EPC level.
Our study shows a relationship between EPC levels and stent strut coverage, supporting a dual role for these cells in favouring stent endothelialisation but also NIH growth.
Improving cardiovascular outcomes in rheumatic diseases: Therapeutic potential of circulating endothelial progenitor cells
2014, Pharmacology and Therapeutics
Citation Excerpt :
In the acute stages following MI, there is a marked release of CD34+/CD45dim/KDR+ cells into the coronary circulation compared to the peripheral circulation. The number of these cells correlates with the size of the infarct (Porto et al., 2013). The stimulus for this release after vascular injury remains unknown, but is unlikely to be due to a systemic inflammation as bacterial antigens induce an acute inflammatory response but not the mobilisation of either CD34+/KDR+ or CD34+/CD133+/KDR+ cells.
Patients with Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) have a significantly increased risk of cardiovascular disease (CVD). The reason for this is unclear but may be due, at least in part, to the failure of endothelial repair mechanisms. Over the last 15 years there has been much interest in the mechanisms of endothelial renewal and its potential as a therapy for CVD. In the circulation there are two distinct populations of cells; myeloid angiogenic cells (MACs) which augment repair by the paracrine secretion of angiogenic factors, and outgrowth endothelial cells (OECs) which are true endothelial progenitor cells (EPCs) and promote vasculogenesis by differentiating into mature endothelium. There are marked abnormalities in the number and function of these cells in patients with RA and SLE. Inflammatory cytokines including interferon-alpha (IFNα) and tumour-necrosis factor alpha (TNFα) both impair MAC and OEC function ex vivo and may therefore contribute to the CVD risk in these patients. Whilst administration of mononuclear cells, MACs and other progenitors has improved cardiovascular outcomes in the acute setting, this is not a viable option in chronic disease. The pharmacological manipulation of MAC/OEC function in vivo however has the potential to significantly improve endothelial repair and thus reduce CVD in this high risk population.
Dose-dependent impact of statin therapy intensity on circulating progenitor cells in patients undergoing percutaneous coronary intervention for the treatment of acute versus chronic coronary syndrome
2022, PLoS ONE
Pathogenetic rationale for using an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and an antioxidant coenzyme Q<inf>10</inf>in the treatment and prevention of cardiovascular disease
2021, Cardiovascular Therapy and Prevention (Russian Federation)
Intrinsic Vascular Repair by Endothelial Progenitor Cells in Acute Coronary Syndromes: an Update Overview
2019, Stem Cell Reviews and Reports

View all citing articles on Scopus

: This study was supported by grant from the Fondazione Cassa di Risparmio di Roma (Rome, Italy) to UNICATT Cord Blood Bank of the Catholic University of the Sacred Heart of Rome.

: See page 790 for disclosure information.

View full text

Coronary artery diseaseEndothelial Progenitor Cells, Microvascular Obstruction, and Left Ventricular Remodeling in Patients With ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Section snippets

Methods

Results

Discussion

Acknowledgment

Blood

Atherosclerosis

J Am Coll Cardiol

Am Heart J

Am Heart J

J Am Coll Cardiol

J Am Coll Cardiol

Am Heart J

J Am Coll Cardiol

Int J Cardiol

J Am Coll Cardiol

From bone marrow to the arterial wall: the ongoing tale of endothelial progenitor cells

Eur Heart J

Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function

Eur Heart J

Mobilization of CD34+CXCR4+ stem/progenitor cells and the parameters of left ventricular function and remodeling in 1-year follow-up of patients with acute myocardial infarction

Mediators Inflamm

Mobilization of CD34(+), CD117(+), CXCR4(+), c-met(+) stem cells is correlated with left ventricular ejection fraction and plasma NT-proBNP levels in patients with acute myocardial infarction

Eur Heart J

Coronary artery disease
Endothelial Progenitor Cells, Microvascular Obstruction, and Left Ventricular Remodeling in Patients With ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention