Genetic lineage tracing reveals poor angiogenic potential of cardiac endothelial cells.

Abstract Aims Cardiac ischaemia does not elicit an efficient angiogenic response. Indeed, lack of surgical revascularization upon myocardial infarction results in cardiomyocyte death, scarring, and loss of contractile function. Clinical trials aimed at inducing therapeutic revascularization through the delivery of pro-angiogenic molecules after cardiac ischaemia have invariably failed, suggesting that endothelial cells in the heart cannot mount an efficient angiogenic response. To understand why the heart is a poorly angiogenic environment, here we compare the angiogenic response of the cardiac and skeletal muscle using a lineage tracing approach to genetically label sprouting endothelial cells. Methods and results We observed that overexpression of the vascular endothelial growth factor in the skeletal muscle potently stimulated angiogenesis, resulting in the formation of a massive number of new capillaries and arterioles. In contrast, response to the same dose of the same factor in the heart was blunted and consisted in a modest increase in the number of new arterioles. By using Apelin-CreER mice to genetically label sprouting endothelial cells we observed that different pro-angiogenic stimuli activated Apelin expression in both muscle types to a similar extent, however, only in the skeletal muscle, these cells were able to sprout, form elongated vascular tubes activating Notch signalling, and became incorporated into arteries. In the heart, Apelin-positive cells transiently persisted and failed to give rise to new vessels. When we implanted cancer cells in different organs, the abortive angiogenic response in the heart resulted in a reduced expansion of the tumour mass. Conclusion Our genetic lineage tracing indicates that cardiac endothelial cells activate Apelin expression in response to pro-angiogenic stimuli but, different from those of the skeletal muscle, fail to proliferate and form mature and structured vessels. The poor angiogenic potential of the heart is associated with reduced tumour angiogenesis and growth of cancer cells

Synchronized Cyclograms to Assess Inter-Limb Symmetry during Gait in Post-Stroke Patients

The aim of this study was to assess the inter-limb symmetry during gait in post-stroke patients using the synchronized cyclograms technique. In total, 41 individuals with stroke (21 left and 20 right hemiplegic patients; age: 57.9 ± 12.8 years; time stroke event 4.6 ± 1.8 years) and 48 age-, sex-, and height-matched individuals (control group: CG; age: 54.4 ± 12.5 years) were assessed via 3D gait analysis. Raw kinematic data were processed to compute spatio-temporal parameters (speed, stride length, cadence, stance, swing, and double support phases duration) and angle–angle diagrams (synchronized cyclograms), which were characterized in terms of area, orientation, and trend symmetry indices. The results reveal that all spatio-temporal parameters are characterized by abnormal values, with reduced speed, stride length, cadence, and swing phase duration and increased stance and double support phases duration. With respect to inter-limb symmetry, higher values were found in post-stroke individuals for all the considered parameters as patients generally exhibited a cyclogram characterized by larger areas, higher orientation, and trend symmetry parameters with respect to CG. The described alterations of gait asymmetry are important from a clinical point of view as the achievement of symmetry in gait represents a crucial objective in the rehabilitation of hemiplegic people