scholarly journals Photocrosslinking of Adventitial Collagen in the Porcine Abdominal Aorta: A Preliminary Approach to a Strategy for Prevention of Aneurysmal Rupture

Designs ◽  
2022 ◽  
Vol 6 (1) ◽  
pp. 5
Author(s):  
Traian V. Chirila ◽  
Shuko Suzuki
Keyword(s):  
Therapeutic Strategy ◽  
Potential Method ◽  
Wall Region ◽  
Photochemical Process ◽  
Crosslinking Process ◽  
Enhanced Resistance ◽  
Abdominal Aortic ◽  
Tunica Adventitia ◽  
Adventitial Layer ◽  
Strength And Stiffness

This study was aimed at generating data for designing a potential method to prevent the rupture of the abdominal aortic aneurysm (AAA). We found that the mechanical strength and stiffness of blood vessel walls was enhanced by the crosslinking of adventitial collagen through a photochemical process promoted by ultraviolet-A (UV-A) radiation. The experiments were carried out on samples isolated from 25 normal porcine aortas. The adventitial layer was separated from the other layers and exposed to UV radiation of 365-nm wavelength, in the presence of a riboflavin compound as the photosensitizer. Mechanical testing of 30 specimens, prior to and after exposure, indicated an increase in both strength (ultimate stress) and stiffness (Young’s modulus) of the adventitial specimens following irradiation. The crosslinking process also led to an enhanced resistance to experimental collagenolysis, as determined on six specimens. At this phase of conceptual design, we suggest that by applying this method to an aneurysmal dilated wall region, the stabilization of tunica adventitia may delay or prevent the rupture of the aneurysm and, with further investigation and refinement, can become a therapeutic strategy for arresting the progression of AAA.

Hierarchical Structure of a Natural Composite: Insect Cuticle

1991 ◽  
Vol 255 ◽  
Author(s):  
Stephen L. Gunderson ◽  
Katie E. Gunnison ◽  
John W. Sawvel
Keyword(s):  
Load Transfer ◽  
Natural Fiber ◽  
Polymeric Composite ◽  
Shear Stiffness ◽  
Insect Cuticle ◽  
Protein Matrix ◽  
Crosslinking Process ◽  
The Matrix ◽  
Improved Performance ◽  
Strength And Stiffness

AbstractThe insect cuticle is an excellent example of a natural, fiber-reinforced, polymeric composite consisting of chitin fibers embedded in a protein matrix. Optical and electron microscopy have been used to examine the structure and interaction of the constituents of the bessbeetle (Odontotaenius disjunctus) cuticle from the molecular to the macroscopic levels.Molecular chains of the polysaccharide chitin (N-acetylglucosamine) are grouped together to form “fibrils” which are either dispersed throughout the matrix or combined to form larger “fibers”. The fibers are unidirectionally oriented within individual sheets or laminae which are stacked on top of one another at various angles forming a laminated structure.The protein matrix is ductile upon initial deposition but then undergoes a crosslinking process which increases its shear stiffness, thereby improving load transfer between fibers. The matrix is bound to the chitin via beta linkages holding it together at both the fibril and fiber levels. The matrix has a fibrous morphology which provides adequate toughness in spite of the high degree of crosslinking.Reference is made to designs observed in the bessbeetle cuticle which could be applied to man-made composites for improved performance primarily in the areas of damage tolerance and strength and stiffness coupled with low weight. For these designs to be implemented using synthetic materials, new or modified processing and fabrication methods are needed.

scholarly journals Tissue-specific tolerance in fatal Covid-19

2020 ◽  
Author(s):  
David A Dorward ◽  
Clark D Russell ◽  
In Hwa Um ◽  
Mustafa Elshani ◽  
Stuart D Armstrong ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Reticuloendothelial System ◽  
Lymphoid Tissues ◽  
Therapeutic Approaches ◽  
Tissue Specific ◽  
Cell Responses ◽  
Enhanced Resistance ◽  
Organ Specific ◽  
Reactive Plasmacytosis ◽  
Specific Tolerance

Successful host defence against a pathogen can involve resistance or tolerance, with implications for prioritising either antimicrobial or immunomodulatory therapeutic approaches. Hyper-inflammation occurs in Covid-19 and is associated with worse outcomes. The efficacy of dexamethasone in preventing mortality in critical Covid-19 suggests that inflammation has a causal role in death. Whether this deleterious inflammation is primarily a direct response to the presence of SARS-CoV-2 requiring enhanced resistance, or an independent immunopathologic process necessitating enhanced tolerance, is unknown. Here we report an aberrant immune response in fatal Covid-19, principally involving the lung and reticuloendothelial system, that is not clearly topologically associated with the virus, indicating tissue-specific tolerance of SARS-CoV-2. We found that inflammation and organ dysfunction in fatal Covid-19 did not map to the widespread tissue and cellular distribution of SARS-CoV-2 RNA and protein, both between and within tissues. A monocyte/myeloid-rich vasculitis was identified in the lung, along with an influx of macrophages/monocytes into the parenchyma. In addition, stereotyped abnormal reticulo-endothelial responses (reactive plasmacytosis and iron-laden macrophages) were present and dissociated from the presence of virus in lymphoid tissues. Our results support virus-independent immunopathology being one of the primary mechanisms underlying fatal Covid-19. This supports prioritising pathogen tolerance as a therapeutic strategy in Covid-19, by better understanding non-injurious organ-specific viral tolerance mechanisms and targeting aberrant macrophage and plasma cell responses.

Hemodynamic Changes in an Actively Rupturing Abdominal Aortic Aneurysm

2021 ◽  
pp. 1-8
Author(s):  
Davis B. McClarty ◽  
David C.S. Kuhn ◽  
April J. Boyd
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Flow Velocity ◽  
Structural Changes ◽  
Hemodynamic Changes ◽  
Cross Sectional ◽  
Recirculation Flow ◽  
Abdominal Aortic ◽  
Appreciable Increase ◽  
Adventitial Layer

Computational fluid dynamics were used to assess hemodynamic changes in an actively rupturing abdominal aortic aneurysm (AAA) over a 9-day period. Active migration of contrast from the lumen into the thickest region of intraluminal thrombus (ILT) was demonstrated until it ultimately breached the adventitial layer. Four days after symptom onset, there was a discrete disruption of adventitial calcium with bleb formation at the site of future rupture. Rupture occurred in a region of low wall shear stress and was associated with a marked increase in AAA diameter from 6.6 to 8.4 cm. The cross-sectional area of the flow lumen increased across all time points from 6.28 to 12.08 cm<sup>2</sup>. The increase in luminal area preceded the increase in AAA diameter and was characterized by an overall deceleration in recirculation flow velocity with a coinciding increase in flow velocity penetrating the ILT. We show that there are significant hemodynamic and structural changes in the AAA flow lumen in advance of any appreciable increase in aortic diameter or rupture. The significant increase in AAA diameter with rupture suggests that AAA may actually rupture at smaller sizes than those measured on day of rupture. These findings have implications for algorithms the predict AAA rupture risk.

Abstract 16757: Immunomodulatory Hydrogel Promotes Survival of Mesenchymal Stem Cells in a Rat Model of Myocardial Infarction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Michaela Olthoff ◽  
Naveen Nagaiah ◽  
Federico Franchi ◽  
Weiang Yan ◽  
Sanjiv Dhingra ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Strategy ◽  
Sinapic Acid ◽  
Firefly Luciferase ◽  
Potential Method ◽  
Cmv Promoter ◽  
Significant Damage ◽  
Anti Inflammatory

Introduction: Stem cell (SC) therapy is a potential method of repairing the heart after injury. However, SCs have been shown to have poor survival after transplantation, at least in part, due to a hostile pro-inflammatory ischemic myocardium. Thus, there is significant interest in the identification of strategies that can increase the retention/survival of SCs after transplantation. Here we seek to investigate whether the use of an immunomodulatory hydrogel, containing anti-inflammatory sinapic acid (SA), promotes the survival of SCs after transplantation. Methods: Myocardial infarction was induced in rats followed by the delayed delivery of A) mesenchymal stem cells (MSCs), B) MSCs in a hydrogel without SA or C) MSCs in a hydrogel containing SA (10μM). Delivery of MSCs (7.5 x 10 5 in 30μL) occurred 7 days after MI, representing the subacute stage and to minimize acute inflammation. Survival of MSCs, stably expressing firefly luciferase under the constitutive CMV promoter, was followed longitudinally using bioluminescence imaging. Results: Panels A-C provide representative images of the viability of MSCs in different groups, with the quantification shown in panel D. There were no differences in survival when MSCs were delivered alone (A) or in a hydrogel without SA (B). However, the survival of MSCs was significantly increased when they were transplanted in a hydrogel with the anti-inflammatory SA (C). Conclusions: Here we provide evidence of the potential for an immunomodulatory hydrogel to enhance the viability of MSCs after infarction, which may lead to improvement of cardiac function. Furthermore, use of this hydrogel in combination with stem cells could be a potential therapeutic strategy for ameliorating cardiac repair after significant damage.

scholarly journals Recent Advances in Pharmacotherapy Development for Abdominal Aortic Aneurysm

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Koichi Yoshimura ◽  
Hiroki Aoki
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Therapeutic Strategy ◽  
Unmet Need ◽  
Common Disease ◽  
Inflammatory Signaling ◽  
Proinflammatory Mediators ◽  
Abdominal Aortic ◽  
Tissue Degradation ◽  
Pharmacologic Inhibition

Abdominal aortic aneurysm (AAA) is a common disease causing segmental expansion and rupture of the aorta with a high mortality rate. The lack of nonsurgical treatment represents a large and unmet need in terms of pharmacotherapy. Advances in AAA research revealed that activation of inflammatory signaling pathways through proinflammatory mediators shifts the balance of extracellular matrix (ECM) metabolism toward tissue degradation. This idea is supported by experimental evidence in animal models that pharmacologic intervention at each pathological step can prevent AAA development. Previously, we identified c-Jun N-terminal kinase (JNK), a pro-inflammatory signaling molecule, as a therapeutic target for AAA. Abnormal activation of JNK in AAA tissue regulates multiple pathological processes in a coordinated manner. Pharmacologic inhibition of JNK tips the ECM balance back towards repair rather than degradation. Interventions targeting signaling molecules such as JNK in order to manipulate multiple pathological processes may be an ideal therapeutic strategy for AAA. Furthermore, the development of biomarkers as well as appropriate drug delivery systems is essential to produce clinically practical pharmacotherapy for AAA.

Abstract 106: Prevention of Abdominal Aortic Aneurysm by Anti-MiRNA-712 or Anti-miR-205 in Angiotensin II--Infused Mice

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Chanwoo Kim ◽  
Sandeep Kumar ◽  
Dong Ju Son ◽  
In-Hwan Jang ◽  
Hanjoong Jo
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Therapeutic Strategy ◽  
Vascular Wall ◽  
Matrix Metalloproteases ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Cysteine Rich Protein ◽  
Endogenous Inhibitors ◽  
Abdominal Aortic

Abdominal aortic aneurysm (AAA) is characterized by weakening of the vessel wall, followed by progressive expansion of the diseased aortic segment. MicroRNAs (miRNAs) have emerged as key regulator of gene expression in the cardiovascular diseases and may play a key role in therapeutically targeting AAA development. Although,vascular wall degradation by matrix metalloproteases (MMPs) is the key mechanism in AAA development, their targeting through miRNAs have never been studied. We identified microRNA-712 (miR-712) as a novel Angiotensin II(AngII)-sensitive miRNA which is upregulated in the abdominal aortic endothelium of AngII-infused mice. Mechanistically, we identified that miR-712 directly regulates two key endogenous inhibitors of MMP: tissue inhibitor of metalloproteinase 3 (TIMP3) and reversion inducing cysteine-rich protein with kazal motifs (RECK). Furthermore, inhibition of miR-712 by subcutaneous injection of anti-miR-712 significantly decreased MMP activity in the AngII-infused abdominal aorta wall, prevented the dilatation of aortae and significantly reduced AAA incidence from 80% (8/10) to 20% (2/10), compared to its mismatched control in ApoE -/- mice. Interestingly, based on the seeding sequence, we identified miR-205 as the human homolog of miR-712. miR-205 was also upregulated by AngII treatment and like miR-712 regulated MMPs activity via TIMP3 and RECK. Moreover, inhibition of miR-205 dramatically inhibits AngII-induced AAA development. We also found that miR-205 was significantly upregulated in the aortic sections of AAA patients in comparison to the healthy controls. Our findings demonstrate that AngII-sensitive miRNAs, miR-712 and miR-205, regulate MMP activity through TIMP3 and RECK and play important role in the pathogenesis of AAA. These results suggest that targeting these miRNAs using their inhibitors may hold promise as a therapeutic strategy to prevent the development of AAA.

scholarly journals Endothelium as a Potential Target for Treatment of Abdominal Aortic Aneurysm

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Jingyuan Sun ◽  
Hongping Deng ◽  
Zhen Zhou ◽  
Xiaoxing Xiong ◽  
Ling Gao
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Endothelial Dysfunction ◽  
Aortic Aneurysm ◽  
Vascular Wall ◽  
High Rate ◽  
Differential Correlation ◽  
Abdominal Aortic ◽  
Enos Uncoupling ◽  
Adventitial Layer ◽  
New Perspective

Abdominal aortic aneurysm (AAA) was previously ascribed to weaken defective medial arterial/adventitial layers, for example, smooth muscle/fibroblast cells. Therefore, besides surgical repair, medications targeting the medial layer to strengthen the aortic wall are the most feasible treatment strategy for AAA. However, so far, it is unclear whether such drugs have any beneficial effect on AAA prognosis, rate of aneurysm growth, rupture, or survival. Notably, clinical studies have shown that AAA is highly associated with endothelial dysfunction in the aged population. Additionally, animal models of endothelial dysfunction and endothelial nitric oxide synthase (eNOS) uncoupling had a very high rate of AAA formation, indicating there is crucial involvement of the endothelium and a possible pharmacological solution targeting the endothelium in AAA treatment. Endothelial cells have been found to trigger vascular wall remodeling by releasing proteases, or recruiting macrophages along with other neutrophils, into the medial layer. Moreover, inflammation and oxidative stress of the arterial wall were induced by endothelial dysfunction. Interestingly, there is a paradoxical differential correlation between diabetes and aneurysm formation in retinal capillaries and the aorta. Deciphering the significance of such a difference may explain current unsuccessful AAA medications and offer a solution to this treatment challenge. It is now believed that AAA and atherosclerosis are two separate but related diseases, based on their different clinical patterns which have further complicated the puzzle. Therefore, a thorough investigation of the interaction between endothelium and medial/adventitial layer may provide us a better understanding and new perspective on AAA formation, especially after taking into account the importance of endothelium in the development of AAA. Moreover, a novel medication strategy replacing the currently used, but suboptimal treatments for AAA, could be informed with this analysis.

Modulated structures in (Bi,Pb)-Sr-Ca-Cu-O films

1990 ◽  
Vol 48 (4) ◽  
pp. 62-63
Author(s):  
Shozo Ikeda ◽  
Hirotoshi Hayakawa ◽  
Daniel R. Dietderich
Keyword(s):  
Rf Magnetron Sputtering ◽  
Potential Method ◽  
High Tc ◽  
Bscco System ◽  
Heat Treated ◽  
Modulated Structures ◽  
High Tc Phase ◽  
Deposited Films ◽  
Sputtering System

Pb addition makes easier to form the high Tc phase in the BSCCO system. However, Pb easily vaporized at high temperature. A controlled Pb potential method has been applied to grow the high Tc phase in films. Initially, films are deposited on cleaved MgO substrates using an rf magnetron sputtering system. These amorphous as-deposited films are heat treated in a sealed gold capsule along with a large pellet of Pb-added BSCCO. Details of the process and characterization of the films have been reported elsewhere (1). Films trated for 0.5h at 850° C contain mainly the low Tc phase with a small amount of the high Tc phase. Hawever, films treated for 3h at 850°C consist mainly of the high Tc phase. This film is superconductive with a Tc(zero) of 106K. The Pb/Bi ratio of the films, analysed by SEM- EDS, are 0.12 and 0.18 for heat tratment times of 0.5 and 3h, respectively. The present study investigates the modulated structures of these films using HREM.

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