scholarly journals The Etiological Heterogeneity of Bicuspid Aortopathy between Ascending and Root Morphotype

2020 ◽  
Vol 23 (6) ◽  
pp. E913-E919
Author(s):  
Fei Li ◽  
Xuan Li ◽  
Yue-tang Wang ◽  
Cun-tao Yu ◽  
Gang Yin ◽  
...  
Keyword(s):  
Shear Stress ◽  
Elastic Fiber ◽  
Ascending Aorta ◽  
Aortic Tissue ◽  
Intrinsic Pathway ◽  
Regional Wall ◽  
Factors Associated ◽  
Elastin Degradation ◽  
Fiber Thickness ◽  
Etiological Heterogeneity

Background: Valve-related hemodynamics and intrinsically regulated matrix proteases are 2 determined pathogenetic factors associated with medial elastin degeneration in bicuspid aortopathy. This study analyzed the association between elastic fiber deterioration and the 2 pathogenetic factors in ascending and root morphotypes, aiming to elucidate the etiological heterogeneity between the 2 morphotypes. Methods: Four-dimensional flow cardiac magnetic resonance was used to measure the regional wall shear stress (WSS) on the ascending aorta, and matrix metalloproteinase (MMP) expression was assessed by immunoblotting. After histopathology analysis of aortic tissue, we assessed whether elevated regional WSS and increased MMP expression corresponded with medial elastin thinning. Results: Increased regional WSS corresponded with medial elastin thinning in both morphotypes. Increased expression of different MMP isoforms corresponded with medial elastin degeneration in bicuspid aortopathy. The significantly increased expression of MMP-2 corresponded with a decrease of elastic fiber thickness in the ascending morphotype (P = .046), whereas elastic fiber thinning was associated with high levels of MMP-3 expression (P = .012) in the root morphotype. No association was observed between regional WSS and MMP expression. Conclusion: There is no difference in the effect of valve-related hemodynamics between ascending and root morphotype, and MMPs are not involved in the process of elastic fiber degeneration induced by increased WSS. The increased expression of different MMP isoforms was observed in the context of elastic fiber degeneration between the 2 morphotypes, implying that heterogeneity between them is revealed in the different intrinsic pathway of medial elastin degradation.

scholarly journals Simultaneous Upregulation of Elastolytic and Elastogenic Factors Are Necessary for Regulated Collateral Diameter Expansion

2022 ◽  
Vol 8 ◽  
Author(s):  
Elizabeth Andraska ◽  
Nolan Skirtich ◽  
Dylan McCreary ◽  
Rohan Kulkarni ◽  
Edith Tzeng ◽  
...  
Keyword(s):  
Shear Stress ◽  
Elastic Fiber ◽  
Elastic Fibers ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Shear ◽  
High Shear Stress ◽  
Luminal Diameter ◽  
Time Points ◽  
Bonferroni Adjustment ◽  
Elastin Degradation

Background: During arteriogenesis, outward remodeling of the arterial wall expands luminal diameter to produce increased conductance in developing collaterals. We have previously shown that diameter expansion without loss of internal elastic lamina (IEL) integrity requires both degradation of elastic fibers and LOX-mediated repair. The aim of this study was to investigate the expression of genes involved in remodeling of the extracellular matrix (ECM) using a model of arteriogenesis.Methods: Sprague-Dawley rats underwent femoral artery ligation with distal arteriovenous fistula (FAL + AVF) placement. Profunda femoral arteries (PFA) were harvested for analysis at various time points. Serum desmosine, an amino acid found exclusively in elastin, was evaluated with enzyme-linked immunosorbent assay (ELISA) as a marker of tissue elastolysis. Tissue mRNA isolated from FAL + AVF exposed PFAs was compared to the contralateral sham-operated using qPCR. HCAECs were cultured under low shear stress (8 dyn·s/cm2) for 24 h and then exposed to high shear stress (40 dyn·s/cm2) for 2–6 h. Primers used included FBN-1, FBN-2, Timp-2, LOX-1, Trop-E, Cath-K, Cath-S, MMP-2, MMP-9, FBLN-4, and FBLN-5 and were normalized to GAPDH. mRNA fold changes were quantified using the 2-ΔΔCq method. Comparisons between time points were made with non-parametric ANOVA analysis with Bonferroni adjustment.Results: PFAs showed IEL reorganization during arteriogenesis. Serum desmosine levels are significantly elevated at 2 days and one week, with a return to baseline thereafter (p < 0.01). Expression of ECM structural proteins (FBN-1, FBN-2, FBLN-4, FBLN-5, Tropoelastin, TIMP-2, LOX-1) and elastolytic proteins (MMP-2, MMP-9, Cathepsin S, Cathepsin K) exhibited an early peak (p < 0.05) relative to sham PFAs. After two weeks, expression returned to baseline. HCAECs demonstrated upregulation of FBN-2, FBLN-5, LOX-1 and Trop-E at 4 h of high shear stress, as well as elastolytic protein MMP-2.Conclusions: Elastin degradation begins early in arteriogenesis and is mediated by local upregulation of elastolytic genes. Elastolysis appears to be simultaneously balanced by production of elastic fiber components which may facilitate stabilization of the IEL. Endothelial cells are central to initiation of arteriogenesis and begin ECM remodeling in response to altered shear stress.

Association of Regional Wall Shear Stress and Progressive Ascending Aorta Dilation in Bicuspid Aortic Valve

2021 ◽  
Author(s):  
Gilles Soulat ◽  
Michael B. Scott ◽  
Bradley D. Allen ◽  
Ryan Avery ◽  
Robert O. Bonow ◽  
...  
Keyword(s):  
Shear Stress ◽  
Aortic Valve ◽  
Wall Shear Stress ◽  
Bicuspid Aortic Valve ◽  
Ascending Aorta ◽  
Regional Wall ◽  
Wall Shear

scholarly journals Dill Extract Induces Elastic Fiber Neosynthesis and Functional Improvement in the Ascending Aorta of Aged Mice with Reversal of Age-Dependent Cardiac Hypertrophy and Involvement of Lysyl Oxidase-Like-1

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 173 ◽  
Author(s):  
Wassim Fhayli ◽  
Quentin Boëté ◽  
Nadjib Kihal ◽  
Valérie Cenizo ◽  
Pascal Sommer ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Lysyl Oxidase ◽  
Elastic Fiber ◽  
Ascending Aorta ◽  
Functional Improvement ◽  
Elastic Fibers ◽  
Aged Mice ◽  
Age Related ◽  
And Function

Elastic fibers (90% elastin, 10% fibrillin-rich microfibrils) are synthesized only in early life and adolescence mainly by the vascular smooth muscle cells through the cross-linking of its soluble precursor, tropoelastin. Elastic fibers endow the large elastic arteries with resilience and elasticity. Normal vascular aging is associated with arterial remodeling and stiffening, especially due to the end of production and degradation of elastic fibers, leading to altered cardiovascular function. Several pharmacological treatments stimulate the production of elastin and elastic fibers. In particular, dill extract (DE) has been demonstrated to stimulate elastin production in vitro in dermal equivalent models and in skin fibroblasts to increase lysyl oxidase–like-1 (LOXL-1) gene expression, an enzyme contributing to tropoelastin crosslinking and elastin formation. Here, we have investigated the effects of a chronic treatment (three months) of aged male mice with DE (5% or 10% v/v, in drinking water) on the structure and function of the ascending aorta. DE treatment, especially at 10%, of aged mice protected pre-existing elastic lamellae, reactivated tropoelastin and LOXL-1 expressions, induced elastic fiber neo-synthesis, and decreased the stiffness of the aging aortic wall, probably explaining the reversal of the age-related cardiac hypertrophy also observed following the treatment. DE could thus be considered as an anti-aging product for the cardiovascular system.

scholarly journals Factors Associated With Callus in Patients with Diabetes, Focused on Plantar Shear Stress During Gait

2016 ◽  
Vol 10 (6) ◽  
pp. 1353-1359 ◽  
Author(s):  
Masako Hamatani ◽  
Taketoshi Mori ◽  
Makoto Oe ◽  
Hiroshi Noguchi ◽  
Kimie Takehara ◽  
...  
Keyword(s):  
Shear Stress ◽  
Factors Associated ◽  
Patients With Diabetes

scholarly journals Surgical Aortic Arch Intervention at the time of Extended Ascending Aortic Replacement is Associated with Increased Mortality

2021 ◽  
Author(s):  
Michael Bowdish ◽  
Daniel Logsdon ◽  
Ramsey Elsayed ◽  
Wendy Mack ◽  
Brittany Abt ◽  
...  
Keyword(s):  
Aortic Arch ◽  
Ascending Aorta ◽  
Conservative Approach ◽  
Factors Associated ◽  
Aortic Replacement ◽  
Ascending Aortic Replacement ◽  
Aortic Arch Repair ◽  
Multivariable Models ◽  
Patch Technique

Objective: To compare outcomes of hemiarch versus total arch repair during extended ascending aortic replacement. Methods: Between 2004 and 2017, 261 patients underwent hemiarch (n=149, 57%) or total arch repair (aortic debranching or Carrell patch technique, n=112, 43%) in the setting of extended replacement of the ascending aorta. Median follow-up was 17.2 (IQR 4.2–39.1) months. Multivariable models considering preoperative and intraoperative factors associated with mortality and aortic reintervention were constructed. Results: Survival was 89.0, 81.3, and 73.5% vs. 76.4, 69.5, and 61.7% at 1, 3, and 5 years in the hemiarch versus total arch groups, respectively (log-rank p=0.010). After adjustment for preoperative and intraoperative factors, the presence of a total arch repair (adjusted HR 2.53, 95% CI 1.39 – 4.62, p=0.003), and increasing age (adjusted HR per 10 years of age, 1.76, 95% CI 1.37 – 2.28, p<0.001) were associated with increased mortality. The cumulative incidence of aortic reintervention with death as a competing outcome was 2.6, 2.6, and 4.4% and 5.0, 10.3, and 11.9% in the hemiarch and total arch groups, respectively. After adjustment, the presence of a total arch repair was significantly associated with need for aortic reintervention (SHR 3.21, 95% CI 1.01 – 10.2, p=0.047). Conclusions: Overall survival after aortic arch repair in the setting of extended ascending aortic replacement is excellent, however, total arch repair and increasing age are associated with higher mortality and reintervention rates. A conservative approach to aortic arch repair can be prudent, especially in those of advanced age.

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