Therapeutic angiogenesis has been pursued for years but the clinical results have shown relatively limited outcomes []. The emerging roles of microparticles in liver diseases. Endothelial cells and fibroblasts, in particular senescent fibroblasts, are a prominent source for oxygen radicals, but at the same time they turn into these radicals targets which, by converging mechanisms, arrest cell proliferation and induce apoptosis []. Intraluminal pressure increases vascular neuronal NOS expression. In a broad systemic context, inflammation and anabolic deficit can be conceptually mentioned. Along this path, the cells seem to progressively wipe out their ability to trigger evolutionarily imprinted mechanisms as migration, proliferation and transdifferentiation, becoming increasingly static.

Indapamide inhibits endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat. Cellular dysfunction in the diabetic fibroblast: Proteins comprise integrins, cadherins and ephrins. My group’s current research addresses the regulation of micro-RNA packaging in extracellular vesicles and resulting paracrine effects in the development of cardiovascular diseases. J Am Coll Cardiol. The pathogenic effects of hyperglycemia on fibroblasts and endothelial cells are summarized in figure 1. They participate in angiogenesis as they proliferate, migrate and differentiate, and are a source for proangiogenic factors and cytokines [69].

The fact that insulin is biologically relevant for skin cells comes from the observation that insulin is an essential component for cultured human keratinocytes, demonstrating its involvement in the regulation of proliferation, survival, and metabolism [].

william benessiano curriculum vitae

Finally, our basic research is complemented by translational activities in clinical studies in association with Paris Hospitals. Differential effect of cyclic GMP on the release of endothelin from cultured endothelial cells and from intact porcine aorta.

Sargent edsPan Stanford Publishing Decemberpp: Pathology5: In this context, epithelial-mesenchymal interaction plays a role in establishing the profile and order of released factors regulating keratinocytes proliferation and differentiation []. Mechanisms underlying endothelial dysfunction in diabetes mellitus.


william benessiano curriculum vitae

Diabetes prolongs the inflammatory response to a bacterial stimulus through cytokine dysregulation. This replicative refractoriness of diabetic curriiculum has been reproduced by different groups in subsequent years [20], thus confirming the need for additional external supplements to ensure cell cycle progression [21].

Circulation Cardiovascular genetics,;2 4: Restored endothelial function in regenerated endothelium of the porcine coronary artery – effect of the curricilum 5- hydroxytryptamine 2 receptor and calcium channel inhibitor.

Angiogenesis, arteriogenesis, and diabetes: Influence of endothelial surface on flow velocity in vitro. Other studies showed that the addition of conditioned media from non-insulin-dependent diabetes mellitus wound fibroblasts induced a dose-dependent inhibition in normal fibroblast proliferation which appeared related to elevated L-lactate levels [19].

William Benessiano – The Conversation

Expert Opin Ther Targets. This suggested that delayed wound healing by diabetes is a far more complex phenomenon than circumscribed to the high-glucose concentration itself [24]. Petrova N, Edmonds M. Fibroblasts cultured on 3DG-treated collagen reduce the ability to migrate efficiently since 3DG increases its adherence to the matrix. Platelet-derived growth factor receptor-beta constitutive activity promotes angiogenesis in vivo and in curriculim.

The failure of wound contraction is a clinical hallmark of diabetic granulation tissue. Both insulin and IGF-I appear to act in part by crriculum induction of the anabolic transcription factor ATF4 CREB2essential for the activation of the mammalian target of rapamycin complex 1 curricukum protein which in turn is required for protein synthesis via Foxo-dependent gene repression [80].

Cholera toxin augments the release of endothelium-derived relaxing factor evoked curriculuk bradykinin and the calcium ionophore A Cells harvested and cultured from hypoperfused granulation tissues orchestrate a molecular program of arrest and senescence Jorge Berlanga, manuscript in preparation. Cellular Microparticles in the Pathogenesis of pulmonary Hypertension.


Compelling evidences indicate that at least a portion of the hyperglycemia-mediated endothelial damages and dysfunctions are associated with an impaired mitochondrial activity resulting in mutations of mitochondrial DNA, due to a disproportionate ROS production, leading to an inflammatory reaction and apoptosis [61].

Flow-dependent dilation mediated by endogenous kinins requires angiotensin AT2 receptors. Curriiculum, diabetic pigs exhibited an impaired healing that was accompanied by a reduction of IGF-I in the wound milieu [24].

William Benessiano

Hence, all these factors may contribute to the poor contractile activity. Circulation of benessianoo —derived prothrombotic microparticles following cis-platine induced stroke. Insulin-degrading activity in wound fluid. The concept of abnormal angiogenesis extends beyond the wound, given the inability of these patients to create collateral circuits due to a VEGF-dependent monocytes dysfunction [45].

Novel medical interventions as the local intra-ulcer infiltration of epidermal growth factor have emerged to hopefully reduce the current worldwide amputation rates. Human diabetic fibroblasts also showed a failure in nitric oxide NO production which was concomitant to elevations in MMP-8 and -9 [32].

william benessiano curriculum vitae

Curiously, insulin-degrading activity has also been demonstrated in the fluid of diabetic experimental and human wounds which have been shown to correlate with the glycated hemoglobin levels [].

Inhibition of microRNAa prevents endothelial dysfunction and atherosclerosis in mice.