scholarly journals Moderate aerobic exercise prevents matrix degradation and death in a mouse model of aortic dissection and aneurysm

2021 ◽  
Vol 320 (5) ◽  
pp. H1786-H1801
Author(s):  
Brittany O. Aicher ◽  
Jackie Zhang ◽  
Selen C. Muratoglu ◽  
Rebeca Galisteo ◽  
Allison L. Arai ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mouse Model ◽  
Aerobic Exercise ◽  
Thoracic Aortic Aneurysm ◽  
Lysyl Oxidase ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Matrix Degradation ◽  
Aortic Aneurysm And Dissection ◽  
Oxidase Inhibition

Moderate aerobic exercise was shown to significantly reduce mortality, extracellular matrix degradation, and thoracic aortic aneurysm and dissection formation associated with lysyl oxidase inhibition in a mouse model. Gene expression suggested a reversal of TGF-β, inflammation, and extracellular matrix remodeling pathway dysregulation, along with augmented elastogenesis with exercise.

scholarly journals Lysyl oxidase inhibition drives the transdifferentiation from lung adenocarcinoma to squamous cell carcinoma in mice

2018 ◽  
Author(s):  
Shun Yao ◽  
Xiangkun Han ◽  
Xinyuan Tong ◽  
Fuming Li ◽  
Zhen Qin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Mouse Model ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lysyl Oxidase ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Oxidase Inhibition ◽  
Model Independent

AbstractLKB1 is frequently mutated in human non-small cell lung cancer (NSCLC) and Lkb1 deletion in mice triggered the lung adenocarcinoma (ADC) to squamous cell carcinoma (SCC) transdifferentiation (AST) through lysyl oxidase (LOX)-dependent extracellular matrix remodeling. Here we show that pharmacological inhibition of lysyl oxidase in KrasG12D/Trp53L/L mouse model, which is known to produce lung ADC only, triggers the ADC-to-SCC transdifferentiation independent of LKB1 status. Treatments of two different inhibitors of lysyl oxidase decrease collagen deposition and promote redox accumulation, and eventually trigger the AST. Importantly, these transited SCC show strong resistance to lysyl oxidase inhibition in stark contrast to ADC. Collectively, these findings establish a new AST mouse model independent of LKB1 inactivation status.

Extracellular matrix remodeling is associated with the survival of cardiomyocytes in the subendocardial region of the ischemic myocardium

2021 ◽  
pp. 153537022110420
Author(s):  
Qing Chu ◽  
Ying Xiao ◽  
Xin Song ◽  
Y James Kang
Keyword(s):  
Extracellular Matrix ◽  
Connexin 43 ◽  
Amine Oxidase ◽  
Lysyl Oxidase ◽  
Significant Loss ◽  
Extracellular Matrix Remodeling ◽  
Coronary Artery Ligation ◽  
Matrix Remodeling ◽  
Artery Ligation ◽  
Junction Protein

A significant amount of cardiomyocytes in subendocardial region survive from ischemic insults. In order to understand the mechanism by which these cardiomyocytes survive, the present study was undertaken to examine changes in these surviving cardiomyocytes and their extracellular matrix. Male C57BL/6 mice aged 8–12 weeks old were subjected to a permanent left anterior descending coronary artery ligation to induce ischemic injury. The hearts were collected at 1, 4, 7, or 28 days after the surgery and examined by histology. At day 1 after left anterior descending ligation, there was a significant loss of cardiomyocytes through apoptosis, but a proportion of cardiomyocytes were surviving in the subendocardial region. The surviving cardiomyocytes were gradually changed from rod-shaped to round-shaped, and appeared disconnected. Connexin 43, an important gap junction protein, was significantly decreased, and collagen I and III deposition was significantly increased in the extracellular matrix. Furthermore, lysyl oxidase, a copper-dependent amine oxidase catalyzing the cross-linking of collagens, was significantly increased in the extracellular matrix, paralleled with the surviving cardiomyocytes. Inhibition of lysyl oxidase activity reduced the number of surviving cardiomyocytes. Thus, the extracellular matrix remodeling is correlated with the deformation of cardiomyocytes, and the electrical disconnection between the surviving cardiomyocytes due to connexin 43 depletion and the increase in lysyl oxidase would help these deformed cardiomyocytes survive under ischemic conditions.

scholarly journals Molecular characterization of lysyl oxidase-mediated extracellular matrix remodeling during mouse decidualization

FEBS Letters ◽  
2017 ◽  
Vol 591 (10) ◽  
pp. 1394-1407 ◽  
Author(s):  
Shu-Yun Li ◽  
Jia-qi Yan ◽  
Zhuo Song ◽  
Yue-Fang Liu ◽  
Min-Jie Song ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Molecular Characterization ◽  
Lysyl Oxidase ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling

scholarly journals Vitamin D deficiency promotes large rupture-prone abdominal aortic aneurysms and cholecalciferol supplementation limits progression of aneurysms in a mouse model

2020 ◽  
Vol 134 (18) ◽  
pp. 2521-2534 ◽  
Author(s):  
Vianne Nsengiyumva ◽  
Smriti M. Krishna ◽  
Corey S. Moran ◽  
Joseph V. Moxon ◽  
Susan K. Morton ◽  
...  
Keyword(s):  
Vitamin D ◽  
Extracellular Matrix ◽  
Mouse Model ◽  
Vitamin D Deficiency ◽  
Ex Vivo ◽  
Aortic Aneurysms ◽  
Matrix Metalloproteinase 2 ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Abdominal Aortic

Abstract Vitamin D deficiency has been associated with human abdominal aortic aneurysm (AAA); however, its role in AAA pathogenesis is unclear. The aim of the present study was to investigate the effect of vitamin D deficiency on AAA development and examine if administering cholecalciferol (CCF) could limit growth of established AAA within the angiotensin-II (AngII) infused apolipoprotein E-deficient mouse model. Mice were rendered vitamin D deficiency through dietary restriction and during AngII infusion developed larger AAAs as assessed by ultrasound and ex vivo morphometry that ruptured more commonly (48% vs. 19%; P=0.028) than controls. Vitamin D deficiency was associated with increased aortic expression of osteopontin and matrix metalloproteinase-2 and -9 than controls. CCF administration to mice with established aortic aneurysms limited AAA growth as assessed by ultrasound (P<0.001) and ex vivo morphometry (P=0.036) and reduced rupture rate (8% vs. 46%; P=0.031). This effect was associated with up-regulation of circulating and aortic sclerostin. Incubation of human aortic smooth muscle cells with 1,25-dihyroxyvitamin D3 (the active metabolite of vitamin D) for 48 h induced up-regulation of sclerostin (P<0.001) and changed the expression of a range of other genes important in extracellular matrix remodeling. The present study suggests that vitamin D deficiency promotes development of large rupture-prone aortic aneurysms in an experimental model. CCF administration limited both growth and rupture of established aneurysms. These effects of vitamin D appeared to be mediated via changes in genes involved in extracellular matrix remodeling, particularly sclerostin.

Abstract 195: Sulforaphane Protects Against Subarachnoid Hemorrhage and Alters the Expression of Inflammatory and Extracellular Matrix Remodeling Genes in a Mouse Model of Intracranial Aneurysm

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Crissey L Pascale ◽  
David M Sawyer ◽  
Lauren A Pace ◽  
Brannan E O’Neill ◽  
Devon O’Donnell ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Subarachnoid Hemorrhage ◽  
Treatment Group ◽  
Mouse Model ◽  
Intracranial Aneurysm ◽  
Lower Incidence ◽  
Control Group ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Rt Pcr

Introduction: Oxidative stress has been shown to play an important role in the pathogenesis of intracranial aneurysm (IA). Sulforaphane is an isothiocyanate that exhibits antioxidant properties via the Nrf2 transcription factor. We tested whether sulforaphane would protect against IA formation and subarachnoid hemorrhage (SAH) in a mouse model. Methods: C57BL/6 mice were treated intraperitoneally with either 0.5mg/kg/day of sulforaphane (treatment group, n = 32) or a vehicle solution (control group, n = 26) prior to being subjected to a well-established IA induction protocol involving unilateral nephrectomy, mineralocorticoid administration, and intracranial injection of elastase. Sulforaphane/vehicle treatments were begun seven days prior to elastase injection, and continued daily for the duration of the experiment. Animals were followed for 14 days until sacrifice, with measurement of the number of aneurysms formed and ruptured in each animal. Intracranial vessel tissue was collected, pooled, and analyzed using real-time PCR (RT-PCR) with experiments performed in triplicate (n = 3). Results: There was a lower incidence of IA in the treatment group (1.06 +/- 0.24 per animal) than in the control group (1.54 +/- 0.33), but this trend did not reach significance. The incidence of SAH in the treatment group (0.53 +/- 0.09 per animal) was approximately 50% lower than in the control group (1.08 +/- 0.21, p = 0.012). RT-PCR showed significant (p < 0.05) differences in the expression of interferon gamma, matrix metalloproteinase 9, collagen Ia2, interleukin-6, myosin heavy chain, and SM22 between the treatment and control groups. Conclusions: Treatment with sulforaphane resulted in a significantly lower incidence of SAH in a mouse model of IA. The expression of genes involved in inflammation and extracellular matrix remodeling were altered by sulforaphane administration.

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