The Detrimental Role of Intraluminal Thrombus Outweighs Protective Advantage in Abdominal Aortic Aneurysm Pathogenesis: The Implications for the Anti-Platelet Therapy

Abstract

Abdominal aortic aneurysm (AAA) is a common cardiovascular disease resulting in morbidity and mortality in older adults due to rupture. Currently, AAA treatment relies entirely on invasive surgical treatments, including open repair and endovascular, which carry risks for small aneurysms (diameter < 55 mm). There is an increasing need for the development of pharmacological intervention for early AAA. Over the last decade, it has been increasingly recognized that intraluminal thrombus (ILT) is involved in the growth, remodeling, and rupture of AAA. ILT has been described as having both biomechanically protective and biochemically destructive properties. Platelets are the second most abundant cells in blood circulation and play an integral role in the formation, expansion, and proteolytic activity of ILT. However, the role of platelets in the ILT-potentiated AAA progression/rupture remains unclear. Researchers are seeking pharmaceutical treatment strategies (e.g., anti-thrombotic/anti-platelet therapies) to prevent ILT formation or expansion in early AAA. In this review, we mainly focus on the following: (a) the formation/deposition of ILT in the progression of AAA; (b) the dual role of ILT in the progression of AAA (protective or detrimental); (c) the function of platelet activity in ILT formation; (d) the application of anti-platelet drugs in AAA. Herein, we present challenges and future work, which may motivate researchers to better explain the potential role of ILT in the pathogenesis of AAA and develop anti-platelet drugs for early AAA.

Effect of Antiplatelet Agents on Abdominal Aortic Aneurysm Process: A Systematic Review and Meta-Analysis

“…The results of our meta-analysis suggest that antiplatelet agents do not affect AAA process, either in terms of sac expansion, reduction, or rupture. Although some of the findings hold opposite opinions, an increasing number of studies suggest that the effectiveness of antiplatelet agents in slowing the expansion of AAA may be due to the antiplatelet agents’ capacity to decrease platelet-derived cytokines expression and plasminogen activation, and to diminish the infiltration of platelets and macrophages within the vascular wall [ 11 , 13 , 22 , 23 ]. Our findings may be different, as meta-analysis does not demonstrate any significant differences in growth rates in patients taking antiplatelet agents (MD = –0.04, 95% CI = [–0.37, 0.30]) (Fig.…”

“…They showed that aspirin and therapeutic anticoagulants were not significantly associated with HO-1 expression ( p 0.05) and were unable to induce HO-1 gene overexpression to provide protection against oxidative stress cells. On the other hand, some researchers suggest that antiplatelet agents may indirectly slow down AAA expansion by inhibiting the progression of intraluminal thrombus (ILT) [ 23 , 27 ]. ILT-induced AAA diameter growth and rupture are the results of a combination of mechanisms, including laminar-to-turbulent flow changes due to altered hemodynamics; anterior wall deposition due to asymmetric spatial distribution of ILT in the AAA capsule [ 23 , 28 , 29 ].…”

“…On the other hand, some researchers suggest that antiplatelet agents may indirectly slow down AAA expansion by inhibiting the progression of intraluminal thrombus (ILT) [ 23 , 27 ]. ILT-induced AAA diameter growth and rupture are the results of a combination of mechanisms, including laminar-to-turbulent flow changes due to altered hemodynamics; anterior wall deposition due to asymmetric spatial distribution of ILT in the AAA capsule [ 23 , 28 , 29 ]. However, part of the studies conclude that the effect of antiplatelet agents on ILT is limited.…”

The role of asymmetry and volume of thrombotic masses in the formation of local deformation of the aneurysmal-altered vascular wall: An in vivo study and mathematical modeling

“…An in-depth analysis of these deformational changes may reveal additional factors that play a role in the rupture of the aortic wall. Undoubtedly, one of these factors is the intraluminal thrombus, the influence of which has been repeatedly confirmed [ 16 , 17 ]. While previous observations have noted the influence of the symmetry of the intraluminal thrombus location [ 18 ]and its density [ 19 , 20 ], a mechanical representation of this influence on both aneurysm rupture and the occurrence of thromboembolic complications has not been presented.…”