Peripheral arterial occlusive disease (PAOD) is a globally-prevalent cardiovascular disease in which atherosclerotic plaques narrow arterial lumen diameters and restrict blood flow to downstream tissues. The impact of these occlusions can be mitigated by collateral vessels that connect parallel arterial branches and act as natural bypasses to maintain perfusion. In animal models that lack collateral arterioles, capillaries that connect terminal arteriolar segments can arterialize and form functional collaterals following an ischemic event; however, in the early stages of development, vasodilation is impaired. We explored the mechanism of impaired vasodilation in arterialized collateral capillaries (ACCs) and pre-existing collaterals (PECs) by evaluating endothelial-dependent vasodilation and endothelial-independent reactivity at day seven following the ischemic event. We also evaluated functional vasodilation in mature ACCs and PECs at day 21 by applying vasodilation inhibitors during the electrical stimulation of muscle contraction. Arterial occlusion was performed by ligating the cranial-lateral spinotrapezius feed artery in Balb/C mice, a strain that either lacks native arteriolar collaterals or contains a single collateral arteriole (~50% of mice), as opposed to the C57Bl/6 strain, which each contain 10 or more collateral arterioles. At seven days post-surgery, both vasodilation and vasoconstriction were impaired in ACCs when compared to terminal arterioles of similar size in unoperated limbs, but still exhibited significant changes when compared to baseline. The comparable reactivity in both endothelial-dependent and independent vasodilation at day-seven in ACCs indicates that vascular smooth muscle cells are likely responsible for the impairment, as they may still be developing, rearranging, or both, and are not yet fully capable of regulating diameter in immature ACCs. However, by 21 days post-ligation, ACCs regained the capacity to dilate in response to muscle contraction, and utilized similar vasodilation pathways as control vessels. At seven days post-ligation, PECs had impaired endothelialindependent dilation, but successful endothelial-dependent dilation, indicating the use of alternative pathways to dilate. Unlike ACCs, the PECs never completely restored vasodilation capabilities by day 21, which may be due to a variation in smooth muscle phenotype, sensitivity to vasoactive agents, and/or limited growth factor expression. For future work, evaluating collateral formation and vasodilation in a diseased model and investigating molecular variations in the smooth muscle may yield additional knowledge that can improve therapies for patients during ischemic events.

Les anévrysmes se développant au niveau des fistules artério-veineuses (FAV), représentent une complication rare mais potentiellement mortelle dont la physiopathologie reste inexplorée. Jusqu’à présent la pratique courante était de les remplacer par un segment prothétique. Nous avons proposé un nouveau traitement chirurgical consistant en une anévrysmorraphie veineuse renforcée extérieurement par une exoprothèse. Notre premier objectif a été de rapporter les résultats à un an de cette nouvelle technique. Dans un second temps nous avons perfusé ex vivo des veines saphènes humaines renforcées par la même exoprothèse dans des conditions hémodynamiques de shear stress (SS) artériel en faisant varier la pression. L’analyse morphologique a montré le développement d’une hyperplasie intimale dans la veine sans et avec exoprothèse à haute pression. L’analyse des gènes et des protéines impliqués dans le remodelage vasculaire n’a pas montré de différence entre la veine nue et la veine renforcée mais nous a permis de mieux caractériser le rôle du SS et de la pression dans le mécanisme de l’artérialisation veineuse. Notre troisième objectif a été de décrire le remodelage anévrysmal des FAV. A partir d’une tissuthèque constituée d’échantillons de veines prélevées chez les patients opérés, nous avons comparé la veine artérialisée anévrysmale à la veine non artérialisée non anévrysmale. Les métalloprotéinases et leurs inhibiteurs participent activement à ce remodelage. Les anévrysmes régulièrement ponctionnés ont un profil inflammatoire qui influence la nature de ce remodelage. / Aneurysm complicating arteriovenous fistula (AVF) is a rare but potentially life-threatening complication. To date, its pathobiology remains unexplored and prosthetic replacement constitutes the conventionnal treatment. We have proposed a new surgical technique consisting in a venous aneurysmorraphy reinforced by an exoprosthesis. Our first goal was to evaluate the one-year results in terms of patency and aneurysm recurrence. Secondly, we have studied the impact of the exoprosthesis on human saphenous veins perfused ex vivo and submitted to different flow conditions consisting in an arterial shear stress (SS) in association with a low or a high pressure setting. Morphological analysis revealed an intimal hyperplasia in veins with and without exoprosthesis under high pressure. Analysis of the proteins and genes involved in the vascular remodeling did not showed an exoprosthesis effect but allowed us to better decipher the selective role played by SS and pressure in the arterialization process. Thirdly, we have collected tissue samples from patients operated and compared aneurysmal arterialized veins to non-aneurysmal non-arterialized veins. Metalloproteinases and their inhibitors actively participate in the remodeling. In aneurysms frequently cannulated inflammation influence the remodeling process.