Ubiquitous Elevation of Matrix Metalloproteinase-2 Expression in the Vasculature of Patients With Abdominal Aneurysms

Abstract

Patients with AAA have elevated MMP-2 levels in the vasculature remote from the aorta. This finding is due to increased MMP-2 expression from SMCs, a characteristic maintained in tissue culture. These data support both the systemic nature of aneurysmal disease and a primary role of MMP-2 in aneurysm formation.

Loss of Timp3 Gene Leads to Abdominal Aortic Aneurysm Formation in Response to Angiotensin II

“…Ϫ/Ϫ -Ang II mice is particularly interesting because MMP2 has been strongly linked to AAA in patients (46,47), and Mmp2 Ϫ/Ϫ mice are protected against CaCl 2 -induced AAA (48). However, in the absence of TIMP3, MMP2 deletion resulted in adverse outcomes such as inflammation and MMP9 up-regulation.…”

“…However, in the absence of TIMP3, MMP2 deletion resulted in adverse outcomes such as inflammation and MMP9 up-regulation. MMP2 has been shown to play a role in early stages of vascular remodeling such as in aneurysm formation (46,47), whereas MMP9 is suggested to be involved in later stages such as aneurysm expansion (46,49). MMP9 has been identified as the key elastase involved in vascular degeneration and aneurysm (37,50), and it can also degrade other vascular ECM proteins such as basement membrane collagen type IV (51).…”

Increased Medial Degradation With Pseudo-Aneurysm Formation in Apolipoprotein E–Knockout Mice Deficient in Tissue Inhibitor of Metalloproteinases-1

“…For instance, it has been hypothesized that overexpression of gelatinase A (MMP-2) by vascular smooth muscle cells may be responsible for the degradation of the elastin fibers in the early stages of aneurysm development. 24 In human abdominal aortic aneurysms, gelatinase B (MMP-9) and metalloelastase (MMP-12) have been detected by in situ hybridization and immunohistochemistry in the macrophages infiltrating the media. [25][26][27] In apoE0 mice, MMP-3, -9, -12, and -13 have been detected in cells at the base of the plaque, in infiltrating macrophages, and in the inflamed adventitia surrounding sites of medial destruction.…”

The Role of Metalloproteinases in the Development of Aneurysm

“…Both proteins are crucial for a proper function of the arterial wall. An interruption of these two balances may lead to a development of various vascular pathologies including atherosclerosis, formation of aneurysm and inflammation [3][4][5].…”

“…MMPs involved in this pathology can origin both from the cells that physiologically constitute the arterial wall and are stimulated to secrete MMPs, i.e. endothelium, SMC and cells that infiltrate the arterial wall in a response to various stimuli [1,3,[6][7][8][9].…”