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• Aortic Inflammation and Calcification in Abdominal Aortic Aneurysmal Disease
  Anirudh Chandrashekar, Nicos Labropoulos
  Published on: 3 June 2020

• Published on: 3 June 2020

  Aortic Inflammation and Calcification in Abdominal Aortic Aneurysmal Disease

  • Anirudh Chandrashekar, DPhil Student University of Oxford
  • Other Contributors:
    • Nicos Labropoulos, Professor of Surgery and Radiology and Director, Non-Invasive Vascular Laboratory

  The prospective matched-cohort study by Joshi et al., investigated inflammation in both AAA and atherosclerosis using 18-FDG PET to generate non-invasive imaging biomarkers for aneurysm expansion and destabilization[1]. Such work is of great importance as atherosclerosis and AAA often co-exist and share many of the same underlying risk factors and pathologies including vascular inflammation and calcification. However, the magnitude and distribution of these processes both locally and globally were not previously investigated and could provide novel insight into AAA progression.

  It was shown that asymptomatic aortic aneurysms had greater inflammatory activity not only in the aneurysmal region but also throughout the entire aorta when compared to the atherosclerotic cohort. This diffuse inflammation of the aorta in AAA patients is supported by our ongoing work investigating the role of the aneurysm in affecting systemic endothelial change. This is assessed by measuring the flow-mediated dilatation (FMD) of the brachial artery [2, 3]. FMD decreases with increased maximum diameter of the aneurysmal sac and reverses following surgical intervention. This suggests that the local aneurysm itself to be a nidus of stimulus for inciting global change during the aneurysm’s natural history[4].

  Furthermore, they show that aneurysms with intra-luminal thrombi (ILT) demonstrated lower 18-FDG uptake both within the thrombus and in the adjacent aortic wall. Here, the authors...

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  The prospective matched-cohort study by Joshi et al., investigated inflammation in both AAA and atherosclerosis using 18-FDG PET to generate non-invasive imaging biomarkers for aneurysm expansion and destabilization[1]. Such work is of great importance as atherosclerosis and AAA often co-exist and share many of the same underlying risk factors and pathologies including vascular inflammation and calcification. However, the magnitude and distribution of these processes both locally and globally were not previously investigated and could provide novel insight into AAA progression.

  It was shown that asymptomatic aortic aneurysms had greater inflammatory activity not only in the aneurysmal region but also throughout the entire aorta when compared to the atherosclerotic cohort. This diffuse inflammation of the aorta in AAA patients is supported by our ongoing work investigating the role of the aneurysm in affecting systemic endothelial change. This is assessed by measuring the flow-mediated dilatation (FMD) of the brachial artery [2, 3]. FMD decreases with increased maximum diameter of the aneurysmal sac and reverses following surgical intervention. This suggests that the local aneurysm itself to be a nidus of stimulus for inciting global change during the aneurysm’s natural history[4].

  Furthermore, they show that aneurysms with intra-luminal thrombi (ILT) demonstrated lower 18-FDG uptake both within the thrombus and in the adjacent aortic wall. Here, the authors claim that the ILT is metabolically inert and that its inactivity is linked with overall thrombus burden. This question of the ILT’s inflammatory profile and its physiological role in AAA progression is an area of active research that has presented many conflicting reports [5-7]. When examining the biological and mechanical properties of the aortic wall, prior studies have often excluded the ILT from analysis. However, recent in-vitro experiments have begun to characterize its heterogenous inflammatory cell infiltrate and metabolic activity[8]. Our group is currently performing a systematic review investigating the extent of inflammation within the ILT and its impact on the aortic wall and peri-aortic tissue. A majority of studies highlight the ILT as a biologically active structure that secretes a variety of proteolytic factors into the aneurysmal environment[9-12]. Ultimately, this leads to local changes in the underlying vessel wall as well as systemic vascular change [13]. This directly conflicts with the results of this study. Although, it is also possible that there may be insufficient localized metabolic activity to garner a positive signal on an 18-FDG-Uptake PET scan. This finding needs to be elucidated in a larger cohort of AAA patients and such work is underway.

  Finally, the authors investigated the extent of calcification throughout the aorta in AAA patients. In general, vascular calcification has been extensively validated as a risk factor in the cardiovascular field and has been shown to strengthen the AAA rupture risk assessment[14, 15]. However, this is the first study to differentiate calcification patterns in AAA and atherosclerotic patients. They concluded that aortic wall calcification is prominent within the aneurysmal sac, relatively non-existent in the remainder of the aorta, and may be used as a biomarker to gauge AAA progression.

  This study introduces a new method to stratify asymptomatic AAA patients, which may be a powerful addition to current tools for AAA disease management. However, as the authors clearly mentioned, future studies are required to assess their prognostic value.

  References
  1. Joshi, N.V., et al., Greater aortic inflammation and calcification in abdominal aortic aneurysmal disease than atherosclerosis: a prospective matched cohort study. Open Heart, 2020. 7(1): p. e001141.
  2. Bellamkonda, K., et al., Flow Mediated Dilatation as a Biomarker in Vascular Surgery Research. Journal of atherosclerosis and thrombosis, 2017. 24: p. 779-787.
  3. Lee, R., et al., Integrated Physiological and Biochemical Assessments for the Prediction of Growth of Abdominal Aortic Aneurysms in Humans. Annals of surgery, 2019. 270: p. e1-e3.
  4. Lee, R., et al., Flow Mediated Dilatation and Progression of Abdominal Aortic Aneurysms. European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery, 2017. 53: p. 820-829.
  5. Haller, S.J., et al., Intraluminal thrombus is associated with early rupture of abdominal aortic aneurysm. Journal of Vascular Surgery, 2018. 67: p. 1051-1058.e1.
  6. Leach, J.R., et al., On the Relative Impact of Intraluminal Thrombus Heterogeneity on Abdominal Aortic Aneurysm Mechanics. Journal of Biomechanical Engineering, 2019. 141.
  7. Wang, D.H., et al., Mechanical properties and microstructure of intraluminal thrombus from abdominal aortic aneurysm. J Biomech Eng, 2001. 123(6): p. 536-9.
  8. Cassimjee, I., R. lee, and J. Patel, Inflammatory Mediators in Abdominal Aortic Aneurysms. IntechOpen, 2017.
  9. Koole, D., et al., Intraluminal abdominal aortic aneurysm thrombus is associated with disruption of wall integrity. J Vasc Surg, 2013. 57(1): p. 77-83.
  10. Kazi, M., et al., Influence of intraluminal thrombus on structural and cellular composition of abdominal aortic aneurysm wall. J Vasc Surg, 2003. 38(6): p. 1283-92.
  11. Kazi, M., et al., Difference in matrix-degrading protease expression and activity between thrombus-free and thrombus-covered wall of abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol, 2005. 25(7): p. 1341-6.
  12. Piechota-Polanczyk, A., et al., The Abdominal Aortic Aneurysm and Intraluminal Thrombus: Current Concepts of Development and Treatment. Frontiers in cardiovascular medicine, 2015. 2: p. 19.
  13. Touat, Z., et al., Renewal of mural thrombus releases plasma markers and is involved in aortic abdominal aneurysm evolution. Am J Pathol, 2006. 168(3): p. 1022-30.
  14. Buijs, R.V., et al., Calcification as a risk factor for rupture of abdominal aortic aneurysm. Eur J Vasc Endovasc Surg, 2013. 46(5): p. 542-8.
  15. Lindholt, J.S., Aneurysmal wall calcification predicts natural history of small abdominal aortic aneurysms. Atherosclerosis, 2008. 197(2): p. 673-8.

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  Conflict of Interest:
  None declared.

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