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. 2021 Sep;62(3):499-506.
doi: 10.1007/s13353-021-00642-3. Epub 2021 Jun 6.

Expression gradient of metalloproteinases and their inhibitors from proximal to distal segments of abdominal aortic aneurysm

Aleksandra Augusciak-Duma  1 , Karolina L Stepien  2 , Marta Lesiak  2 , Ewa Gutmajster  3 , Agnieszka Fus-Kujawa  2 , Malwina Botor  2 , Aleksander L Sieron  2
Affiliations

Expression gradient of metalloproteinases and their inhibitors from proximal to distal segments of abdominal aortic aneurysm

Aleksandra Augusciak-Duma et al. J Appl Genet. 2021 Sep.

Abstract

Abdominal aortic aneurysm refers to abnormal, asymmetric distension of the infrarenal aortic wall due to pathological remodelling of the extracellular matrix. The distribution of enzymes remodelling the extracellular matrix and their expression patterns in the affected tissue are largely unknown. The goal of this work was to investigate the expression profiles of 20 selected genes coding for metalloproteinases and their inhibitors in the proximal to the distal direction of the abdominal aortic aneurysm. RNA samples were purified from four lengthwise fragments of aneurysm and border tissue obtained from 29 patients. The quantities of selected mRNAs were determined by real-time PCR to reveal the expression patterns. The genes of interest encode collagenases (MMP1, MMP8, MMP13), gelatinases (MMP2, MMP9), stromelysins (MMP3, MMP7, MMP10, MMP11, MMP12), membrane-type MMPs (MMP14, MMP15, MMP16), tissue inhibitors of metalloproteinases (TIMP1, TIMP2, TIMP3, TIMP4), and ADAMTS proteinases (ADAMTS1, ADAMTS8, and ADAMTS13). It was found that MMP, TIMP, and ADAMTS are expressed in all parts of the aneurysm with different patterns. A developed aneurysm has such a disturbed expression of the main participants in extracellular matrix remodelling that it is difficult to infer the causes of the disorder development. MMP12 secreted by macrophages at the onset of inflammation may initiate extracellular matrix remodelling, which, if not controlled, initiates a feedback loop leading to aneurysm formation.

Keywords: Abdominal aortic aneurysm; Angiogenesis; Extracellular matrix; Metalloproteases; Remodelling.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Abdominal aortic aneurysm collected during an open aortic repair (OAR) schematically showing the plan of partitioning of the tissue. From each segment, pieces of ~ 4 mm × 4 mm × 2–4 mm were subjected immediately to RNA isolation and purification (boxed)
Fig. 2
Fig. 2
Relative expression of selected genes encoding matrix metalloproteinases and matrix metalloprotease inhibitors in aneurysm and surrounding tissues representing the four gene groups. Non-parametric Mann–Whitney test and T-test (for MMP11) were performed (* p < 0.05, ** p < 0.05). a, group I; b, group II; c, group III; and d, group IV. The grey line represents the trend in the expression gradient
See this image and copyright information in PMC

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