Circulating endothelial progenitor cells are actively involved in the reparative mechanisms of stable ischemic myocardium

Background: Myocardial fibrosis (MF) is an adverse correlate of severe aortic valve stenosis (SAVS). microRNA expression modulates different pathophysiological pathways in cardiovascular disease. In particular miRNA­21, has been associated to MF due to pressure overload. Non­invasive estimation of MF, using speckle­tracking echocardiography (2D­STE), could be useful in determining early myocardial damage. Purpose: To analyze the correlation between 2D­STE parameters, MF, plasmatic and tissue miRNA­21 in SAVS. Methods: We evaluated 36 consecutive patients (75.2±8 y.o., 63% F) with SAVS and preserved ejection fraction (EF), undergoing to surgical aortic valve replacement (AVR; Euroscore II 2.28±1.13%; Logistic Euroscore: 6±4.1%). Clinical, ECG, biohumoral evaluation (including plasma miRNA­21) and a complete echocardiography, including 2D­STE, was performed before AVR. 28 patients eventually underwent AVR and, in 23 of them, a basal interventricular septum biopsy was performed. MF and tissue miRNA­21 expression (micro­dissection) were evaluated in each sample. Results: All patients with SAVS (AVAi 0.33±0.1 cm2/m2; V max 4.4±0.4 m/sec; Mean Grad. 50±9 mmHg) showed concentric hypertrophy (LVMi 147±20.7 g/m2, RWT 0.51±0.07), diastolic dysfunction and increased Valvulo­Arterial Impedance (ZVA: 5.9±2.3 mmHg/ml/m2). Despite a preserved EF (66±11%), an altered global and septal deformation (Global longitudinal strain, GLS −13±6.1; Global longitudinal strain rate, GLSr −0.8±0.2 1/sec; Global early diastolic Sr, GLSrE 1±0.35 1/sec; Septal longitudinal strain, SLS −8.6±2.8%; SL­Sr −0,6±0.1 1/sec; SL­SrE 0.6±0.29 1/sec) were observed. We found a significant association between MF and 2D­STE parameters, stroke volume and end­diastolic pressure (all p<0.05). Tissue miRNA­21 was mainly expressed in fibrous tissue than in myocardium (p<0.0001). Myocardial miRNA­21 was associated with AVAi (r=0.46; p=0.043) and cardiac index (r=0.5; p=0.02) while fibrous tissue miRNA­21 was associated to GLS (r=0.8; p=0.0003), GLSrE (r=−0.72; p=0.005), SLS (r=0.6; p=0.01), SL­Sr (r=0.54; p=0.03), SL­SrE (r=0.5; p=0.04) and PAPs (r=0.66; p=0.004). Plasma miRNA­21 was associated to MF (r=0.5; p=0.02) and septal longitudinal strain (r=0.38; p=0.037). Conclusions: In SAVS with preserved EF, MF is associated to impaired myocardial deformation. miRNA­21 has a potential pathophysiological role in fibrogenesis. Non­invasive evaluation of plasmatic miRNA­21 and 2D­STE could be useful in risk stratification, to optimize the timing of surgery in SAVS patients

Endothelial progenitor cells: An appraisal of relevant data from bench to bedside

The mobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow is well known to be present in several clinical settings, including acute coronary syndrome, heart failure, diabetes and peripheral vascular disease. The aim of this review was to explore the current literature focusing on the great opportunity that EPCs can have in terms of regenerative medicine

Role of circulating endothelial progenitor cells in the reparative mechanisms of stable ischemic myocardium

Background: Mobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow in patients with acute myocardial infarction has strong scientific evidence; less is known about EPC mobilization in patients with stable coronary artery disease (CAD). The aim of this study was to investigate the association of stable ischemic heart disease with EPC levels in tissue and blood. Methods: Fifty-five consecutive patients admitted to a single treatment center for valve or coronary artery bypass grafting (CABG) surgeries were included in the study. Blood samples were collected in the morning before surgery and analyzed by flow-cytometry to determine peripheral EPC levels (EPC/ml). Tissue EPC (CD34 + VEGFR2. +) levels were assessed on a right atrial appendage segment. Results: Mean age was 76. ±. 5. years, 48% were men, and 53% had CAD The number of CD34. + VEGFR2. + cells in the tissue of patients with CAD was significantly higher (p <. 0.005) and circulating EPC showed a tendency to be reduced by approximately 20% in peripheral blood of patients with CAD when compared to those without CAD. Conclusion: Patients with stable CAD had higher EPC density values (EPC/mm2) and were more likely to have lower EPC blood levels when compare with normal controls

Perspectives in noninvasive imaging for chronic coronary syndromes

Both the latest European guidelines on chronic coronary syndromes and the American guidelines on chest pain have underlined the importance of noninvasive imaging to select patients to be referred to invasive angiography. Nevertheless, although coronary stenosis has long been considered the main determinant of inducible ischemia and symptoms, growing evidence has demonstrated the importance of other underlying mechanisms (e.g., vasospasm, microvascular disease, energetic inefficiency). The search for a pathophysiology-driven treatment of these patients has therefore emerged as an important objective of multimodality imaging, integrating “anatomical” and “functional” information. We here provide an up-to-date guide for the choice and the interpretation of the currently available noninvasive anatomical and/or functional tests, focusing on emerging techniques (e.g., coronary flow velocity reserve, stress-cardiac magnetic resonance, hybrid imaging, functional-coronary computed tomography angiography, etc.), which could provide deeper pathophysiological insights to refine diagnostic and therapeutic pathways in the next future