Using Molecular Targets to Predict and Treat Aortic Aneurysms

Abstract

Aortic aneurysms are life-threatening vascular diseases associated with high morbidity, and usually require prophylactic surgical intervention. Current preventative management of aortic aneurysms relies on the diameter and other anatomic parameters of the aorta, but these have been demonstrated to be insufficient predictive factors of disease progression and potential complications. Studies on pathophysiology of aortic aneurysms could fill this need, which already indicated the significance of specific molecules in aortic aneurysms. These molecules provide more accurate prediction, and they also serve as therapeutic targets, some of which are in preclinical stage. In this review, we summarized the inadequacies and achievements of current clinical prediction standards, discussed the molecular targets in prediction and treatment, and especially emphasized the molecules that have shown potentials in early diagnosis, accurate risk assessment and target treatment of aortic aneurysm at early stage.

Keywords: aortic aneurysm; diagnosis; molecular target; risk stratification; treatment; vascular imaging.

Fig. 1.

Aorta anatomic parameters of AA. (A) 3D modelled CT images of the aorta of a female aged 24 years (a) and a female aged 85 years (b). Reproduced with permission from BMJ Publishing Group Ltd. [17]. (B) 3D wall stress distributions of the two abdominal aortic aneurysm models: (a) unaltered model, (b) no-calcification model. Reproduced with permission from Elsevier [18].

Fig. 2.

Application of different molecular targets in different imaging techniques. (A) The FDG-uptake in the dissected aortic wall shown in CT, PET, PET/CT and 2 months, 2 years, 3 years follow-up with CT. Reproduced with permission from BMJ Publishing Group Ltd. [43]. ${\mathrm{(B)}}^{99m}$Tc-MAG3-anti-CD11b SPECT/CT images with pathological and immunohistochemical confirmation. Reproduced under CC-BY 4.0 license from Springer Nature [56]. (C) ${\mathrm{(a,b)}}^{99m}$Tc-RYM1 imaging of carotid aneurysm, carotid arteries ex vivo photography (a) and autoradiography (b) without (left) and with (right) pre-injection of excess of MMP inhibitor RYM; ${\mathrm{(c,d)}}^{99m}$Tc-RYM1 SPECT/CT images of abdominal aortic aneurysm animals model, (c) low remodeling group, (d) aneurysm group, Arrows: areas of maximal tracer uptake in aorta. This research was originally published in JNM. Toczek J et al. [57] Preclinical Evaluation of RYM1, a Matrix Metalloproteinase-Targeted Tracer for Imaging Aneurysm. J Nucl Med. 2017; 58: 1318–1323. © SNMMI . (D) Representative MRI images of mice after injection with CG and CDR, following BAPN administration for 0, 2, and 4 weeks. Mice were examined by BL after MR imaging. The red arrows for the CG or CDR groups indicate the same position. CG: DOTA-Gd, CDR: Col-IV-DOTA-RhB, BLI: bioluminescence imaging. Reproduced under CC-BY 4.0 license from Ivyspring International Publisher [58]. (E) In vivo imaging of MMP activation in aneurysm. left (L): carotid arteries aneurysmal; right (R): control. This research was originally published in JNM. Razavian M et al. [59] Molecular imaging of matrix metalloproteinase activation to predict murine aneurysm expansion in vivo. J Nucl Med. 2010; 51: 1107–1115. © SNMMI .

Fig. 3.

Nanoparticles of different molecular targets. (A) Structure of rapamycin-incorporated nanoparticles. Reproduced under CC-BY 4.0 license from Plos One [107]. (B) Schematic of ROS-responsive nanoplatform. Reproduced with permission from Elsevier [108]. (C) Schematic diagram illustrating the preparation of TP-Gd/miRNA-ColIV complexes and the resultant targeted gene therapy. Reproduced under CC-BY 4.0 license from Springer Nature [109].