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Regulation of circulating progenitor cells in left ventricular dysfunction.

ABSTRACT: Reductions in numbers of circulating progenitor cells (CD34+ cell subsets) have been demonstrated in patients at risk for, or in the presence of, cardiovascular disease. The mediators of these reductions remain undefined. To determine whether neurohumoral factors might regulate circulating CD34+ cell subsets in vivo, we studied complementary canine models of left ventricular (LV) dysfunction.A pacing model of severe LV dysfunction and a hypertensive renal wrap model in which dogs were randomized to receive deoxycorticosterone acetate (DOCA) were studied. Circulating CD34+ cell subsets including hematopoietic precursor cells (HPCs: CD34+/CD45(dim)/VEGFR2-) and endothelial progenitor cells (EPCs: CD34+/CD45-/VEGFR2+) were quantified. Additionally, the effect of mineralocorticoid excess on circulating progenitor cells in normal dogs was studied. The majority of circulating CD34+ cells expressed CD45dimly and did not express VEGFR2, consistent with an HPC phenotype. HPCs were decreased in response to pacing, and this decrease correlated with plasma aldosterone levels (Spearman rank correlation=-0.67, P=0.03). In the hypertensive renal wrap model, administration of DOCA resulted in decreased HPCs. No changes were seen in EPCs in either model. Normal dogs treated with DOCA exhibited a decrease in HPCs in peripheral blood but not bone marrow associated with decreased telomerase activity.This is the first study to demonstrate that mineralocorticoid excess, either endogenous or exogenous, results in reduction in HPCs. These data suggest that mineralocorticoids may induce accelerated senescence of progenitor cells, leading to their reduced survival and decline in numbers.

SUBMITTER: Boilson BA

PROVIDER: S-EPMC3096994 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Regulation of circulating progenitor cells in left ventricular dysfunction.

Boilson Barry A BA Larsen Katarina K Harbuzariu Adriana A Delacroix Sinny S Korinek Josef J Froehlich Harald H Bailey Kent R KR Scott Christopher G CG Shapiro Brian P BP Boerrigter Guido G Chen Horng H HH Redfield Margaret M MM Burnett John C JC Simari Robert D RD

Circulation. Heart failure 20100623 5

<h4>Background</h4>Reductions in numbers of circulating progenitor cells (CD34+ cell subsets) have been demonstrated in patients at risk for, or in the presence of, cardiovascular disease. The mediators of these reductions remain undefined. To determine whether neurohumoral factors might regulate circulating CD34+ cell subsets in vivo, we studied complementary canine models of left ventricular (LV) dysfunction.<h4>Methods and results</h4>A pacing model of severe LV dysfunction and a hypertensive ...[more]

PMID: 20573992

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Project description:BackgroundCardiac magnetic resonance (CMR) has been used to diagnose and risk-stratify patients with left ventricular noncompaction (LVNC). The prognostic value of CMR parameters for LVNC, especially feature tracking (CMR-FT), is not well known in LVNC patients with left ventricular dysfunction. The present study aimed to investigate whether the combination of CMR-FT with traditional CMR parameters can increase the prognostic value of CMR for LVNC patients with reduced left ventricular ejection fraction (LVEF).MethodsA total of 123 candidates were retrospectively included in this multicenter study and 55 LVNC patients (mean age, 45.7 ± 16.2 years; 61.8% men) remained after applying the exclusion criteria. Clinical features, left ventricular (LV) function parameters, global and segment myocardial strain, and late gadolinium enhancement (LGE) were evaluated. The outcomes include the composite events of cardiovascular death, heart transplantation, hospitalization for heart failure, thromboembolic events, and ventricular arrhythmias.ResultsAfter a median follow-up of 5.17 years (interquartile range: 0.17 to 10.58 years), 24 (36.8%) patients experienced at least one major adverse cardiovascular event (MACE). The myocardial strain parameters of patients with events were lower than those of patients without events. In the univariable Cox analysis, LVEF, the presence of LGE, global longitudinal strain (GLS) and segmental strains, including longitudinal strain at the apical level and radial and circumferential strain at the basal level, were significantly associated with MACEs. In the multivariate analysis, LGE (hazard ratio (HR) 3.452, 95% CI 1.133 to 10.518, p = 0.029) was a strong predictor of MACEs and significantly improved the predictive value (chi-square of the model after adding LGE: 7.51 vs. 13.47, p = 0.009). However, myocardial strain parameters were not statistically significant for the prediction of MACEs after adjusting for age, body mass index, LVEF and the presence of LGE and did not increase the prognostic value (chi-square of the model after adding GLS: 13.47 vs. 14.14, p = 0.411) in the multivariate model.ConclusionsThe combination of CMR-FT with traditional CMR parameters may not increase the prognostic value of CMR in LVNC patients with reduced LVEF, while the presence of LGE was a strong independent predictor of MACEs and significantly improved the predictive value.

Dataset Information

Regulation of circulating progenitor cells in left ventricular dysfunction.

Publications

Regulation of circulating progenitor cells in left ventricular dysfunction.

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