I016 Extracellular matrix remodelling in abdominal aortic aneurysm: involvement of LOXL2 and TG2 reticulation enzymes

AbstractAbdominal 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.

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Interactions of biomechanics with extracellular matrix components in abdominal aortic aneurysm wall

Atherosclerosis ◽

10.1016/j.atherosclerosis.2015.04.914 ◽

2015 ◽

Vol 241 (1) ◽

pp. e185

Author(s):

F. Tanios ◽

M.G. Gee ◽

J. Pelisek ◽

S. Kehl ◽

V. Grabher-Meier ◽

...

Keyword(s):

Extracellular Matrix ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Aneurysm Wall ◽

Abdominal Aortic ◽

Extracellular Matrix Components ◽

Abdominal Aortic Aneurysm Wall ◽

Matrix Components

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Suppression of abdominal aortic aneurysm formation by inhibition of prolyl hydroxylase domain protein through attenuation of inflammation and extracellular matrix disruption

Clinical Science ◽

10.1042/cs20130435 ◽

2014 ◽

Vol 126 (9) ◽

pp. 671-678 ◽

Cited By ~ 20

Author(s):

Aya Watanabe ◽

Toshihiro Ichiki ◽

Chikahiro Sankoda ◽

Yusuke Takahara ◽

Jiro Ikeda ◽

...

Keyword(s):

Extracellular Matrix ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Cobalt Chloride ◽

Prolyl Hydroxylase ◽

Abdominal Aneurysm ◽

Aneurysm Formation ◽

Abdominal Aortic ◽

Domain Protein ◽

Prolyl Hydroxylase Domain

Inhibition of prolyl hydroxylase domain protein by cobalt chloride suppressed calcium chloride-induced abdominal aneurysm formation in mice.

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PPARδ reduces abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E-deficient mice by regulating extracellular matrix homeostasis and inflammatory responses

International Journal of Cardiology ◽

10.1016/j.ijcard.2014.03.138 ◽

2014 ◽

Vol 174 (1) ◽

pp. 43-50 ◽

Cited By ~ 11

Author(s):

Jung Seok Hwang ◽

Hyo Jung Kim ◽

Gyeongwha Kim ◽

Eun Sil Kang ◽

Sun Ah. Ham ◽

...

Keyword(s):

Extracellular Matrix ◽

Abdominal Aortic Aneurysm ◽

Angiotensin Ii ◽

Aortic Aneurysm ◽

Apolipoprotein E ◽

Inflammatory Responses ◽

Aneurysm Formation ◽

Abdominal Aortic ◽

Deficient Mice

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Interaction of Biomechanics with Extracellular Matrix Components in Abdominal Aortic Aneurysm Wall

European Journal of Vascular and Endovascular Surgery ◽

10.1016/j.ejvs.2015.03.021 ◽

2015 ◽

Vol 50 (2) ◽

pp. 167-174 ◽

Cited By ~ 11

Author(s):

F. Tanios ◽

M.W. Gee ◽

J. Pelisek ◽

S. Kehl ◽

J. Biehler ◽

...

Keyword(s):

Extracellular Matrix ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Aneurysm Wall ◽

Abdominal Aortic ◽

Extracellular Matrix Components ◽

Abdominal Aortic Aneurysm Wall ◽

Matrix Components

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Inducible Depletion of Calpain-2 Mitigates Abdominal Aortic Aneurysm in Mice

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.315546 ◽

2021 ◽

Author(s):

Latha Muniappan ◽

Michihiro Okuyama ◽

Aida Javidan ◽

Devi Thiagarajan ◽

Weihua Jiang ◽

...

Keyword(s):

Extracellular Matrix ◽

Smooth Muscle ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Structural Integrity ◽

Mesenchymal Cell ◽

Ang Ii ◽

Structural Protein ◽

Abdominal Aortic ◽

Calpain 2

Objective: Cytoskeletal structural proteins maintain cell structural integrity by bridging extracellular matrix with contractile filaments. During abdominal aortic aneurysm (AAA) development, (1) aortic medial degeneration is associated with loss of smooth muscle cell integrity and (2) fibrogenic mesenchymal cells mediate extracellular matrix remodeling. Calpains cleave cytoskeletal proteins that maintain cell structural integrity. Pharmacological inhibition of calpains exert beneficial effects on Ang II (angiotensin II)–induced AAAs in LDLR −/− (low-density receptor deficient) mice. Here, we evaluated the functional contribution of fibrogenic mesenchymal cells-derived calpain-2 on (1) cytoskeletal structural protein and extracellular matrix alterations and (2) AAA progression. Approach and Results: Calpain-2 protein and cytoskeletal protein (filamin and talin) fragmentation are significantly elevated in human and Ang II–induced AAAs in mice. To examine the relative contribution of calpain-2 in AAA development, calpain-2 floxed mice in an LDLr −/− background were bred to mice with a tamoxifen-inducible form of Cre under control of either the ubiquitous promoter, chicken β-actin, or fibrogenic mesenchymal cell-specific promoter, Col1α2. Ubiquitous or fibrogenic mesenchymal cell-specific depletion of calpain-2 in mice suppressed Ang II–induced AAAs, filamin/talin fragmentation, while promoting extracellular matrix protein, collagen in the aortas. Calpain-2 silencing in aortic smooth muscle cells or fibroblasts reduced Ang II–induced filamin fragmentation. In addition, silencing of filamin in aortic SMCs significantly reduced collagen protein. Furthermore, calpain-2 deficiency suppressed rupture of established Ang II–induced AAAs in mice. Conclusions: Our studies implicate that calpain-2 deficiency prevents (1) Ang II–induced cytoskeletal structural protein fragmentation and AAA development and (2) stabilize and suppress rupture of established AAAs in mice.

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Circular RNA RBM33 contributes to extracellular matrix degradation via miR-4268/EPHB2 axis in abdominal aortic aneurysm

PeerJ ◽

10.7717/peerj.12232 ◽

2021 ◽

Vol 9 ◽

pp. e12232

Author(s):

Shizhi Wang ◽

Qingwen Yuan ◽

Wenpeng Zhao ◽

Weimin Zhou

Keyword(s):

Extracellular Matrix ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Matrix Metalloproteinase 2 ◽

Luciferase Reporter ◽

Circular Rnas ◽

Ang Ii ◽

Abdominal Aortic ◽

Gene Assay ◽

Ecm Degradation

Background Abdominal aortic aneurysm (AAA) is a complex vascular disease involving expansion of the abdominal aorta. Extracellular matrix (ECM) degradation is crucial to AAA pathogenesis, however, the specific molecular mechanism remains unclear. This study aimed to investigate differentially expressed circular RNAs (DEcircRNAs) involved in ECM degradation of AAA. Methods Transcriptome sequencing was used to analyze the DEcircRNAs between the AAA tissues and normal tissues. The expression of circRNAs in tissues and cells was validated using quantitative reverse transcription PCR (RT-qPCR). Overexpression of circRNAs in vascular smooth muscle cells (VSMCs) treated with angiotensin II (Ang II) was employed to explore its effect on ECM degradation of AAA. Bioinformatic technology, luciferase reporter gene assay, RT-qPCR, and rescue experiment were employed to evaluate the regulatory mechanism of circRNA. Results We identified 65 DEcircRNAs in AAA tissues compared with normal abdominal aortic tissues, including 30 up-regulated and 35 down-regulated circRNAs, which were mainly involved in inflammation and ECM-related functions and pathways. Moreover, circRBM33 was significantly increased in AAA tissues and Ang II-induced VSMCs compared with control samples. Overexpression of circRBM33 increased the expression of ECM-related molecule matrix metalloproteinase-2 and reduced the tissue inhibitor of matrix metalloproteinases-1 expression. Mechanistically, miR-4268 targeted binding to circRBM33 and inhibited the luciferase activity of circRBM33. Overexpression of circRBM33 induced the expression of EPH receptor B2 (EPHB2), and this effect was countered by miR-4268 mimics. Conclusions Overall, our data suggest that circRBM33 might be involved in AAA progression by regulating ECM degradation via the miR-4268/EPHB2 axis.

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