scholarly journals MiR-191 as a Key Molecule in Aneurysmal Aortic Remodeling

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1611
Author(s):  
Sabina Lichołai ◽  
Dorota Studzińska ◽  
Hanna Plutecka ◽  
Tomasz Gubała ◽  
Wojciech Szczeklik ◽  
...  

Abdominal aortic aneurysms (AAA) are a complex disease with an unclear pathomechanism. A positive family history is emphasized as a significant risk factor, and a nonspecific model of inheritance suggests participation of epigenetic regulation in the pathogenesis of this disease. Past studies have implicated microRNAs in the development of AAA; therefore in this project, we measured miR-191 levels in AAA patients and compared them with a control group. We found that miR-191 levels were significantly elevated in aneurysmal patients, although this did not correlate with the available clinical data. We then developed an in vitro model where, using cells with an endothelial phenotype, we determined the effect of miR-191 on the transcriptome using RNA sequencing. Subsequent pathway analysis established that some of the perturbations mediated by miR-191 can be explained by several processes which have long been observed and described in literature as accompanying the development of abdominal aortic aneurysms.

2013 ◽  
Vol 35 (6) ◽  
pp. 800-809 ◽  
Author(s):  
Valérie Deplano ◽  
Clark Meyer ◽  
Carine Guivier-Curien ◽  
Eric Bertrand

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Kiana M Samadzadeh ◽  
Anthony Nguyen ◽  
Kevin C Chun ◽  
Eugene S Lee

Purpose: The pleiotropic effects of statin drugs on reducing inflammation have been well regarded in decreasing AAA expansion. We hypothesize that increased monocyte activity plays a central role in AAA formation and expansion. This study examines whether statins can prevent monocyte cell adhesion, transmigration, and matrix metalloproteinase (MMP) and inhibitor (TIMP) concentrations in AAA patients compared to non-AAA patients. Methods: Peripheral blood was collected for monocyte and serum isolation from control (n=4) and AAA (n=8) patients. Monocyte adhesion and transmigration were assessed under untreated, statin treated, and statin + mevalonate (statin inhibitor) treated conditions in vitro. Luminex assays determined MMP and TIMP concentrations from cell culture and patient serum. Results: Untreated AAA patient monocytes showed higher levels of adhesion (p=0.05) and transmigration (p=0.04) compared to control subjects (Figure 1A & 1B). Statin treatment caused a decrease in AAA monocyte adherence to the endothelium (p=0.03) and high concentrations of mevalonate reversed statin treatment effects (p=0.04) (Figure 1A). A similar trend was noted in monocyte transmigration (Figure 1B). Higher concentrations of MMP-9 were found in AAA patient serum compared to controls (p=0.01) (Figure 1C). TIMP-4 concentration were decreased in AAA patients compared to controls (p=0.02) (Figure 1D). Conclusions: Statins reduce monocyte interaction with the endothelium in vitro, leading to decreased levels of MMP-9 and increased levels of TIMP-4, implying a possible mechanism by which statins reduce AAA expansion.


2008 ◽  
Vol 15 (4) ◽  
pp. 468-484 ◽  
Author(s):  
Timothy J. Corbett ◽  
Anthony Callanan ◽  
Liam G. Morris ◽  
Barry J. Doyle ◽  
Pierce A. Grace ◽  
...  

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nao Inoue ◽  
Michiko Muramatsu ◽  
Denan Jin ◽  
Shinji Takai ◽  
Tetsuya Hayashi ◽  
...  

Chymase promotes not only angiotensin II production but also matrix metalloproteinase (MMP)-9 activation, which have a critical role on development of abdominal aortic aneurysms (AAAs). The purpose of this study is to examine the effects of chymase inhibitor, NK3201, on the MMP-9 activity and development of AAA in the angiotensin II-induced apolipoprotein E (apoE)-deficient mice. Method: Angiotensin II (1000ng/kg/min) (vehicle group) or saline (control group) were infused into 16-week-old male apoE-deficient mice for 4 weeks. To examine the effect of chymase inhibition for AAA, we administered NK3201 (30mg/kg/day) to angiotensin II-infused group (NK3201-treated group) for the same period. At the end of angiotensin II infusion, we measured the diameters of suprarenal and infrarenal aorta. AAA severities were scored using the suprarenal aortic diameter/infrarenal aortic diameter ratio and presence of thrombus formation, i.e. under 2.0 was 0, from 2.0 to 2.5 was 1, from 2.5 to 3.0 was 2, over 3.0 was 3, and presence of thrombus was 4. We also determined the chymase and MMP-9 activities using total aorta. Results: The scores that reflected the progression and severity of AAA were increased in vehicle group compared with control group ( 2.35±0.30 vs. 0.27±0.12, p<0.01). This progression was inhibited in NK3201-treated group compared with vehicle group (1.13±0.35, p<0.05 vs. vehicle group). Chymase activity was significantly increased in vehicle group compared with control group. MMP-9 activity was also increased in vehicle group, however it was decreased significantly in NK3201-treated group.Discussion: We demonstrated that chymase inhibition could reduce AAA progression through inhibition of MMP-9 in angiotensin II-induced apoE-deficient mice. Chymase inhibitor might be a novel strategy for preventing AAAs.


2020 ◽  
Vol 54 (7) ◽  
pp. 573-578
Author(s):  
Tiffany W. Liang ◽  
S. Keisin Wang ◽  
Paul D. Dimusto ◽  
Christopher M. McAninch ◽  
Charles W. Acher ◽  
...  

Objective: The attempt to repair a ruptured abdominal aortic aneurysm carries a significant risk of perioperative mortality. The relationship between body mass index (BMI) and outcomes after repair of ruptured abdominal aortic aneurysms (AAAs) has not been well defined. We report the association of BMI with outcomes after ruptured AAA repair. Methods: Patients undergoing ruptured AAA repairs between 2008 and 2017 at 2 tertiary academic centers were included in this retrospective study. Demographics (including BMI), type of repair, length of stay, and admission mortality risk scores were gathered and analyzed using bivariate and multivariate logistic regressions. Adjusted odds ratio (AOR) was reported with 95% CIs and P values from the multivariate analysis. The primary outcome was 30-day mortality. Akaike information criterion (AIC) and c-statistics were used to assess the predictive power of models including physiologic score with or without BMI. Results: A total of 202 patients underwent repair of ruptured AAA. In bivariate relationship, increased BMI was significantly associated with 30-day mortality. With multivariate analysis, adjusting for demographics, type of procedure, and physiologic score, for each kg/m2 increase in BMI, an 8% increase in the likelihood of perioperative mortality (AOR = 1.08, 95% CI: 1.01-1.17; P = .04) was observed. Conclusion: When adjusted for admission risk score, type of procedure, and demographics, obesity was associated with increased 30-day mortality. With BMI as an additional data point, the c-statistics and AIC comparisons indicated that we would have a greater ability to preoperatively estimate mortality after ruptured AAA repair. Consideration could be made to include BMI in future mortality risk scoring systems for ruptured AAA.


Author(s):  
O. Karaarslan Cengiz ◽  
G. Nergizoglu

The risk of cardiovascular disease begins to increase from the early stages of chronic kidney disease (CKD). Abdominal aortic aneurysms are the most common arterial aneurysms of peripheral arterial diseases. The frequency of abdominal aortic aneurysm varies according to the population studied. This study aimed to determine the prevalence of abdominal aortic aneurysm in patients with stage 3-4  CKD and investigate  CKD is a risk factor for abdominal aortic aneurysm formation. Methods. Patients aged 55 years and older who were followed up in the internal medicine outpatient clinics were enrolled. Two hundred CKD patients with glomerular filtration rates between 15-59 mL/min per 1.73 m2 were included in the study group, and 110 patients with glomerular filtration rates of 60 mL/min per 1.73 m2 or above were assigned to the control group. An ultrasonography device with a 3.5 MHz probe was used for screening. Abdominal aortic diameters of 3 cm and above were accepted as abdominal aortic aneurysms. Results. Eighteen patients in the study group (9%) and four in the control group (3.6%) had an abdominal aortic aneurysm. The prevalence of abdominal aortic aneurysms was higher in the  CKD  group. However, the difference was not statistically significant (p=0.078). Moreover, the median aortic diameter was 21.8 mm (14-44 mm) in the study group, compared to 21.0 mm (14-46 mm) in the control group. The prevalence of the abdominal aortic aneurysm was 14.9% in stage 4  CKD patients and 6% in stage 3  CKD patients (p=0.038). Conclusion. An abdominal aortic aneurysm is more common in patients with  CKD although it does not reach statistical significance. The median aortic diameter was significantly wider in CKD patients compared to the control group . The prevalence of abdominal aortic aneurysm increased with an increase in the CKD stage .


Author(s):  
Timothy J. Corbett ◽  
Barry J. Doyle ◽  
Anthony Callanan ◽  
Tim M. McGloughlin

A vast amount of experimental research has been undertaken in the past decade to investigate different aspects of preoperative and postoperative abdominal aortic aneurysms (AAAs). Much of this research has been based on the use of mock arteries in an in vitro flow loop to mimic the behaviour of the abdominal aorta in vivo [1]. These models should be reproducible, have consistent material properties, consistent thickness and be physiological in behaviour.


Author(s):  
Lingli Liu ◽  
Fuxing Zhang ◽  
Rui Wang ◽  
Robin Shandas

Abdominal aortic aneurysms (AAAs) are localized balloon-shaped expansions commonly found in the infrarenal segment of the abdominal aorta, between the renal arteries and the iliac bifurcation. Abdominal aortic aneurysm rupture has been estimated to occur in as much as 3%–9% of the population, and represents the 13th leading cause of death in the United States, producing more than 10,000 deaths annually [1]. Thus, determining the significant factors for aneurysm growth and rupture has become an important clinical goal. From a biomechanical standpoint, AAA rupture risk is related to certain mechanical and hemodynamic factors such as localized flow fields and velocity patterns, and flow-induced stresses within the fluid and in the aneurysm structure [2]. Disturbed flow patterns at different levels have also been found to trigger responses within medial and adventitial layers by altering intercellular communication mechanisms. Thus, localized hemodynamics proximal, within and distal to AAA formations play an important role in modulating the disease process, and non-invasive and easy-to-implement methods to characterize and quantify these complex hemodynamics would be tremendously useful.


Aorta ◽  
2015 ◽  
Vol 03 (01) ◽  
pp. 9-15 ◽  
Author(s):  
Rachel Rolph ◽  
Matthew Waltham ◽  
Alberto Smith ◽  
Helena Kuivaniemi

AbstractRecent technological advances have allowed researchers to interrogate the genetic basis of abdominal aortic aneurysms in great detail. The results from these studies are expected to transform our understanding of this complex disease with both multiple genetic and environmental risk factors. Clinicians need to keep abreast of these genetic findings and understand the implications for their practice. Patients will become increasingly informed on genetic risk, and a new era of individualized risk assessment for AAA is just beginning. This brief update aims to provide the clinician with a succinct précis of the recent progress in this area.


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