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  • Using the juxtarenal PPE the induction of juxta

    2021-01-14

    Using the juxtarenal PPE, the induction of juxta- and suprarenal aneurysms is described herein (Fig. 3A). The infra-/suprarenal part of the 873 can now be investigated separately, taking into account different embryological backgrounds and varying reactivity to differing stimuli (reviewed by Lindsay and Dietz and Majevsky). In an exploratory study, with limited power owing to small sample size (n = 3 mice), TGF-β expression and its canonical activation by pSMAD2/3, an important conductor of aneurysm development based on previous research, was investigated.3, 32 A difference in the gene expression or protein level, suggestive of equal TGF-β activity, could not be demonstrated in the present study (Fig. S3A; see Supplementary Material).33, 34 Although pathogenesis and phenotype differ tremendously between PPE and the other most common AAA mouse model, the AngII model, juxtarenal PPE can help to seclude model specific effects between the two, and to distinguish distinct features of aneurysm progression. This is of great value, as translational research approaches in recent years have depended on possible target evaluation from either or both of the two models. However, the value of the present observations, and the role of differential aneurysm formation in relation to its aortic localisation, needs further detailed studies and analysis. The aortoiliac PPE takes the model beyond the aortic bifurcation and allows for mimicking of additional human pathologies (Fig. 3B). Although a frequent disease in humans, alone or in combination with AAA, iliac aneurysms in an animal model have never been described previously. A bifurcation type aneurysm has been induced in rabbit carotid arteries and can provide additional insight regarding the contribution of flow diversion to aneurysm formation.25, 35 Size restricts endovascular research in mice, but the combination of PPE modifications presented here enables the mimicking of different types of aortic aneurysm morphologies for imaging and molecular studies in future translational research (Figure 2, Figure 3).
    Conclusion The PPE model, especially in later stages of aneurysm growth, shows the closest pathophysiological similarity to end stage human AAA disease with regard to the characteristics of the vessel wall. While the classic PPE model is a sufficient model for in vivo drug testing in aneurysm research, flow modulation and extended elastase perfusion to the juxtarenal and aortoiliac vessels mimic distinct aneurysm morphologies, and allow further elucidation of the basic mechanisms underlying aneurysm formation of the aorta for translational research.
    Conflicts of Interest
    Funding
    Acknowledgments
    Introduction Skin ageing processes are generally divided into intrinsic and extrinsic, both responsible for drastic changes in skin structure and elasticity. The intrinsic or chronological skin ageing is irremediably related to the passage of time, although it is also influenced by the inherited genes. Conversely, the extrinsic skin ageing is caused by environmental factors, such as chronic exposure to sunlight (photoageing) or pollutants, and it is influenced by miscellaneous lifestyle components (i.e. smoking and diet) (Farage et al., 2008). In particular, photoageing is caused by overexposure to UV radiations, which increases the production of reactive oxygen species (ROS) (Rittié and Fisher, 2002), causing lipid peroxidation, DNA damage, and proteins alterations. Moreover, ROS can also contribute to skin ageing by direct activation of enzymes responsible for the cleavage of extracellular matrix (ECM) components (Mukherjee et al., 2011; Rittié and Fisher, 2002). Natural products from plants are widely used as cosmetic or cosmeceutical ingredients because of their capability to slow down the intrinsic skin ageing processes and to contrast the extrinsic ones. Plants anti-ageing properties are generally attributed to their antioxidant metabolites, which minimize free radical activity and protect skin against solar radiations (Sahu et al., 2013). Additionally, several plant metabolites are also reported to modulate the activity of enzymes involved in the ageing processes (Cefali et al., 2016; Mukherjee et al., 2011). Among these enzymatic targets of cosmetic interest, elastase and tyrosinase are of remarkable importance.