Extracellular Matrix Remodelling and Abdominal Aortic Aneurysm

Ratnadeep Basu Zamaneh Kassiri

doi:10.4172/2155-9880.1000259

Abstract

Aorta is the largest artery in the body. Aortic wall is comprised of an intricate arrangement of extracellular matrix (ECM) structural proteins, primarily collagen and elastin, and layers of vascular smooth muscle cells. This gives the aortic wall the tensile strength to withstand the pressure of blood pumped from the heart during systole, and the elasticity to expand and accommodate the left ventricular stroke volume and to, subsequently, recoil to its original diameter and push the blood forward for systemic perfusion. Aortic aneurysm involves structural degradation of the aortic wall and focal dilatation of the aortic lumen. It is a devastating health problem with no effective treatment. Current management strategies for AAA patients include antihypertensive drugs and surgical repair for severe cases of AAA which are not without limitations and complications. A number of proteases (matrix metalloproteinases, serine and cystein proteases), and their inhibitors (tissue inhibitor of metalloproteases and cystatin) have been shown to contribute to AAA development and progression. In this review we will summarize the published literature on the role of ECM-regulatory proteins, mainly proteases and their inhibitors, in aortic function and aneurysm formation, with a focus on abdominal aortic aneurysm.

Highlights

Aorta, the largest artery in the body, does not merely serve as a conduit to distribute blood from the heart to the body, but plays important roles in multiple aspects of the cardiovascular system, including perfusion of the myocardium and the peripheral tissue, and arterial function [1]
The growing list of genetically modified mice with targeted matrix metalloproteases (MMPs), proteases, or tissue inhibitor of metalloproteinase (TIMPs) subjected to different models of aortic aneurysm provide valuable insight into the role of these extracellular matrix (ECM)-regulatory proteins in development and progression of Abdominal aortic aneurysm (AAA) (Table 1)
MMP8 deficiency in mice did not alter the size of elastase-induced AAAs, whereas neutrophil depletion prevented AAA through a mechanism independent from MMP2 and MMP9 pathways [59].This study demonstrates that additional factors produced by neutrophils are essential in AAA formation

Summary

Introduction

The largest artery in the body, does not merely serve as a conduit to distribute blood from the heart to the body, but plays important roles in multiple aspects of the cardiovascular system, including perfusion of the myocardium and the peripheral tissue, and arterial function [1]. The main cause of aneurysm is structural damage to the media and adventitia and loss of VSMCs [15], leading to hemodynamic changes, increased wall stress, lumen dilatation and eventually rupture of the aortic wall This can explain the higher prevalence of aneurysm in the abdominal aorta which contains a lower number of lamellar units, decreased elastin content and poorer vasa vasorum supply of nutrients and oxygen to the SMC. The growing list of genetically modified mice with targeted MMPs, proteases, or TIMPs subjected to different models of aortic aneurysm provide valuable insight into the role of these ECM-regulatory proteins in development and progression of AAA (Table 1). Elevated MMP2 activation was detected in the abdominal aorta after 2 weeks of Ang II infusion, ablation of MMP2 in TIMP3-/mice exacerbated AAA dilation and increased the rate of aortic rupture, primarily due to heightened inflammation. Treatment with a broad spectrum MMP inhibitor (PD166793) prevented AAA formation in TIMP3-/- and TIMP3-/-/MMP2-/- mice [48]

C WT-Ang II

Findings

Conclusion