Mast cells associate with neovessels in the media and adventitia of abdominal aortic aneurysms

Abstract

The results support participation of MCs in the pathogenesis of AAA, particularly regarding neovascularization of aortic wall.

Biochemomechanics of Intraluminal Thrombus in Abdominal Aortic Aneurysms

“…This importance of elastin breakdown products stimulating neovascularization (as opposed to just hypoxia from a thickening ILT) may explain, in part, why significant differences in neovascularization were noted between aneurysmal walls and control aorta but not between thick versus thin thrombus covered aneurysmal walls [65] or thrombus covered versus noncovered aneurysmal walls [76]. Faisal et al [73] similarly showed that a laminin peptide found in AAAs, due to release from the degrading ECM, can upregulate uPA and MMP-9 in macrophages.…”

“…Similarly, proteases, degradation products, antigens, and other soluble biomolecules may be transported radially through the aneurysmal wall toward the adventitia, which can play a major role in arterial responses to disease, including fibroblast activation, neovascularization, immunoinflammation, and fibrosis [78]. It is also likely that the permeability increases as the endothelial lining is lost [76] and the organized structure of the healthy aortic wall is degraded [51]. Along these lines, recent attempts at modeling the thrombus and aneurysmal wall as porohyperelastic structures [86,87] may provide insight into the complex interstitial fluid flows in thrombus-laden AAAs.…”

“…Interestingly, ILT correlated positively with wall levels of pro-and active MMP-2, elastase, and plasmin, whereas total wall MMP-9, MMP-2 activation, plasmin activity, and microparticle release correlated with aneurysm diameter. The potential importance of these and other factors in future modeling and therapeutic efforts is highlighted by the attenuation of aneurysmal development in various experimental models of AAA by depletion of neutrophils, T-cells, macrophages, or mast cells [76,90], inhibition of platelet activation [91], inhibition of neutrophil recruitment [92,93], knockout of plasminogen [67], deficiency of uPA [94], knockout of MMP-2, -9, or -12 [95,96], or increases in PAI-1 [97], TIMP-1 [98], or catalase [99].…”

“…Compared to a thrombus-free wall, the wall beneath an ILT may have increased inflammation and neovascularization as well as fewer elastic fibers and smooth muscle cells, many of which are apoptotic [100]. An increase in phenotypically synthetic SMCs, many with elongated processes suggesting ongoing migration, has also been noted [76,100]. In comparison, an aneurysmal wall without ILT can have a dense collagenous matrix with phenotypically contractile SMCs and increased staining for a-actin [100], although expression of MMP-1, -7, -9, and -12 can be higher than in the covered wall [101].…”

“…The shoulder also appears to be a site of increased MMP-9 activity, decreased medial thickness, fewer intact lamellar units, and increased phosphorylated c-Jun N-terminal kinase (JNK), inflammation, and neovascularization [66]. Notably, JNK may be a pivotal intracellular signaling molecule in SMCs and macrophages that can be upregulated by a plethora of biomolecules frequently associated with AAAs, including MMP-2 and 9, Ang-II, histamine, interleukins, IFN-c, and tumor necrosis factor a (TNF-a) [66,76]. Interestingly, expression of both TNF-a and its activating enzyme TACE are not only higher in AAAs compared to control aortas, they are also higher in the neck compared with the apex of the lesion, where they colocalize with macrophages of the media and adventitia.…”