Association of CD14+ monocyte-derived progenitor cells with cardiac allograft vasculopathy.

OBJECTIVE: The pathogenesis of cardiac allograft vasculopathy after heart transplant remains controversial. Histologically, cardiac allograft vasculopathy is characterized by intimal hyperplasia of the coronary arteries induced by infiltrating cells. The origin of these infiltrating cells in cardiac allograft vasculopathy is unclear. Endothelial progenitor cells are reportedly involved in cardiac allograft vasculopathy; however, the role of CD14(+) monocyte-derived progenitor cells in cardiac allograft vasculopathy pathogenesis remains unknown. METHODS: Monocyte-derived progenitor cells were isolated from blood mononuclear cell fractions obtained from 25 patients with cardiac allograft vasculopathy and 25 patients without cardiac allograft vasculopathy. RESULTS: Both patients with cardiac allograft vasculopathy and those without cardiac allograft vasculopathy had CD45(+), CD34(+), CD14(+), CD141(-), CD31(-) monocyte-derived progenitor cells that differentiated into mesenchymal lineages. Monocyte-derived progenitor cells formed significantly higher numbers of colonies in patients with cardiac allograft vasculopathy than in those without cardiac allograft vasculopathy; this correlated with posttransplant follow-up time. Importantly, monocyte-derived progenitor cells from patients with cardiac allograft vasculopathy expressed significantly more α smooth muscle actin and proliferated at a higher rate than did monocyte-derived progenitor cells of patients without cardiac allograft vasculopathy. In vitro experiments suggested a paracrine control mechanism in proliferation of monocyte-derived progenitor cells in cardiac allograft vasculopathy. CONCLUSIONS: These results indicate that monocyte-derived progenitor cells are associated with cardiac allograft vasculopathy, have the ability to transdifferentiate into smooth muscle cells, and thus may contribute to intimal hyperplasia of coronary arteries in cardiac allograft vasculopathy. Targeting monocyte-derived progenitor cell recruitment could be beneficial in cardiac allograft vasculopathy treatment.

Two-dimensional speckle-tracking strain echocardiography in long-term heart transplant patients: a study comparing deformation parameters and ejection fraction derived from echocardiography and multislice computed tomography.

AIMS: Longitudinal strain determined by speckle tracking is a sensitive parameter to detect systolic left ventricular dysfunction. In this study, we assessed regional and global longitudinal strain values in long-term heart transplants and compared deformation indices with ejection fraction as determined by transthoracic echocardiography (TTE) and multislice computed tomographic coronary angiography (MSCTA). METHODS AND RESULTS: TTE and MSCTA were prospectively performed in 31 transplant patients (10.6 years post-transplantation) and in 42 control subjects. Grey-scale apical views were recorded for speckle tracking (EchoPAC 7.0, GE) of the 16 segments of the left ventricle. The presence of coronary artery disease (CAD) was assessed by MSCTA. Strain analysis was performed in 1168 segments [496 in transplant patients (42.5%), 672 in control subjects (57.7%)]. Global longitudinal peak systolic strain was significantly lower in the transplant recipients than in the healthy population (-13.9 ± 4.2 vs. -17.4 ± 5.8%, P< 0.01). This was still the case after exclusion of the nine transplant patients with CAD (-14.1 ± 4.4 vs. -17.4 ± 5.8%, P=0.03). Transplant patients exhibited significantly lower regional strain values in 9 of the 16 segments. Left ventricular ejection fraction (%) (MSCTA/Simpsons method) was 60.7 ± 10.1%/60.2 ± 6.7% in transplant recipients vs. 64.7 ± 6.4%/63.0 ± 6.2% in the healthy population, P=ns. CONCLUSION: Even though 'healthy' heart transplants without CAD exhibit normal ejection fraction, deformation indices are reduced in this population when compared with control subjects. Our findings suggests that strain analysis is more sensitive than assessment of ejection fraction for the detection of abnormalities of systolic function.

Optimized arterial trees supplying hollow organs.

Computer models of arterial trees can be generated from optimization principles using the algorithm of constrained constructive optimization (CCO). Up to now this algorithm could handle only tissue areas of convex shape, without concavities. CCO is now generalized to cope also with non-convex organ shapes, possibly featuring external as well as internal concavities. This allows the modeling of a much larger class of interesting real arterial systems. The concept of a generalized domain-potential was developed to represent arbitrary non-convex shapes mathematically and incorporate them as boundary conditions to optimization. Domain-potentials may be derived from analytical representations as well as from finite element triangulations obtained from organ images. To demonstrate the feasibility of the concept, the optimized growth of an arterial tree model is confined to some part of an elliptical shell, representing the free wall of the left ventricle of the heart.

Heterogeneous perfusion is a consequence of uniform shear stress in optimized arterial tree models.

Using optimized computer models of arterial trees we demonstrate that flow heterogeneity is a necessary consequence of a uniform shear stress distribution. Model trees are generated and optimized under different modes of boundary conditions. In one mode flow is delivered to the tissue as homogeneously as possible. Although this primary goal can be achieved, resulting shear stresses between blood and the vessel walls show very large spread. In a second mode, models are optimized under the condition of uniform shear stress in all segments which in turn renders flow distribution heterogeneous. Both homogeneous perfusion and uniform shear stress are desirable goals in real arterial trees but each of these goals can only be approached at the expense of the other. While the present paper refers only to optimized models, we assume that this dual relation between the heterogeneities in flow and shear stress may represent a more general principle of vascular systems.