• 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • Our results showed that in elastase induced AAA TGF


    Our results showed that in elastase-induced AAA, TGF-β neutralization finely tunes macrophage phenotype. Note that several studies have already addressed the role of M1 markers, such as IL-6 and IL-1β, or M2 markers, including IL-10 and TGF-β.4, 9, 10, 11 The expression and the role of ARG1 in AAA have been so far poorly investigated, and this is the reason that we focused on this M2 marker. We investigated ARG1 protein expression in human infrarenal AAA tissue and showed the presence of ARG1-positive cells located mainly in the adventitia, whereas no staining was observed in healthy aortic tissue. ARG1 is an enzyme that converts arginine to produce urea and ornithine. Ornithine can serve as a precursor for the production of proline, an amino SB408124 that can be used for the synthesis of proline-rich proteins, such as collagen. Collagen represents a main component of the ECM, which is vastly degraded during AAA development. Several studies have demonstrated that arginine supplementation increases collagen deposition in rodent and human and favors wound healing.23, 24 In addition, ARG1 promotes VSMC proliferation, and in vitro studies revealed that ARG1 overexpression in smooth muscle cells suppressed lipopolysaccharide-induced tumor necrosis factor α release and inhibited monocyte chemotaxis and migration.25, 26 Hence, ARG1 could potentially play a role in pathways relevant for AAA disease, such as ECM remodeling, VSMC homeostasis, and regulation of inflammatory response. Whereas ARG1 expression increased with AAA progression, further experimental approaches using ARG1-deficient mice are required to determine whether the increase of ARG1 has a pathogenic or a protective compensatory role in AAA development. Last, AAA is frequently associated with atherosclerosis, and several studies have addressed the role of ARG1 in the disease. A first study revealed a higher expression of ARG1 in macrophages in rabbits with genetically determined low atherosclerotic response compared with those with high atherosclerotic response, suggesting its role in atherosclerosis resistance. Besides macrophages, ARG1 can also be detected in endothelial cells and VSMCs. Intriguingly, a study revealed that even though ARG1-specific deletion in hematopoietic cells increased foam cell formation, no significant effect was identified on atherosclerosis, including plaque size and stability as well as plaque macrophage content in the aortic root. To determine whether the global increase of ARG1 or the increase of the macrophage subtype that expresses ARG1 plays a role in AAA, it would be useful to use mice that specifically lack ARG1 in macrophages. Taken together, these results highlight a complex role of ARG1 that may differ according to cell subsets. Further studies using genetic models of ARG1 deletion would be of interest to better understand its role during AAA formation and progression.
    Author contributions
    Introduction The senile plaque, associated with activated microglia and astrocytes, is the pathological hallmark in the brains of patients with Alzheimer's disease (AD). Extracellular accumulation of insoluble amyloid-β protein (Aβ) is the main component of the plaque that induces synaptic dysfunction and neuronal loss resulting in progressive dementia [1]. Quantitative analyses have shown that, on average, 60% of all plaques contain Aβ42 and 31% contain Aβ40, and that the newly deposited Aβ was only partially co-localized with pre-existing Aβ and apolipoprotein-E (ApoE) [2]. Neurons produce Aβs by the proteolytic cleavage of amyloid precursor protein (APP), and are normally cleared though efflux into the peripheral circulation [3]. Aβs are then degraded by insulin-degrading enzymes secreted from astrocytes [4]. Impaired clearance of soluble Aβ rather than its overproduction is implicated in Aβ accumulation. The burden of extracellular Aβ induces an increase in intraneuronal Aβ accumulation [5] that is derived from internalized Aβ by neurons from the extracellular space. This occurs through ApoE-dependent and ApoE-independent pathways [6] and from intrinsic Aβ that escapes exocytosis after APP processing in the endocytic compartment [7].