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Relationship between BMP2/9 Levels and Spinal Function and Quality of Life in Patients with Severe Scoliosis after PVCR. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:7008898. [PMID: 34745296 PMCID: PMC8570867 DOI: 10.1155/2021/7008898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 10/04/2021] [Indexed: 11/17/2022]
Abstract
Objective To explore the relationship between (bone fusion associated protein) bone morphogenetic protein (BMP)2 and BMP9 and spinal function and quality of life in patients with severe scoliosis after posterior vertebral column resection (PVCR). Methods 78 cases of severe scoliosis treated with PVCR surgery in our hospital from January 2015 to April 2018 were selected and set as the observation group, and 80 health examiners in the same period were selected and set as the control group. The ELISA method was used to detect the levels of BMP2 and BMP9 in the two groups. Also, the relationship between the recovery of spinal function, quality of life, and serum BMP2 and BMP9 in the observation group was analyzed. The receiver operating characteristic curve was used to evaluate the predictive value of BMP2 and BMP9 for complications after PVCR. Results One month after PVCR, the serum BMP2 and BMP9 levels of patients with severe scoliosis were higher than those of healthy people (P < 0.05). One year after PVCR, Pearson correlation analysis showed that serum levels of BMP2 and BMP9 in patients with scoliosis were positively correlated with ODI scores (r = 0.778, P < 0.001; r = 0.746, P < 0.001), SRS-22 scores (r = 0.758, P < 0.001; r = 0.722, P < 0.001), and Cobb angle correction rate (r = 0.838, P < 0.001; r = 0.802, P < 0.001). Conclusion The levels of BMP2 and BMP9 of patients with scoliosis after PVCR are higher than those of healthy people. After 1-year follow-up, the patients' serum BMP2 and BMP9 levels were positively correlated with spinal function recovery, quality of life, and surgical efficacy. Among them, BMP2 and BMP9 had the highest correlation with PVCR surgical efficacy. Paying attention to the serum BMP2 and BMP9 levels of patients with scoliosis has certain clinical significance.
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Lei X, Liu Q, Li S, Zhang Z, Yang X. Effects of fluid shear stress on expression of focal adhesion kinase in MG-63 human osteoblast-like cells on different surface modification of titanium. Bioengineered 2021; 12:4962-4971. [PMID: 34374319 PMCID: PMC8806473 DOI: 10.1080/21655979.2021.1962686] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
This study aimed to investigate the effect of fluid shear stress (FSS) on cell proliferation and expression of focal adhesion kinase (FAK) in MG-63 cells on different modified titanium surfaces. MG63 cells were cultured on three different surfaces: glass slide, polished treatment (PT) titanium surface and sandblasted/acid-etched surfaces (SLA) titanium surface. The surface topography and roughness were evaluated by scanning electron microscopy (SEM) and atomic force microscopy (AFM), respectively. The cells were subjected to FSS, and the cell appearance before and after the stress was evaluated. MTT assay was applied to estimate cell proliferation. The mRNA and protein levels of FAK were determined by qRT-PCR and western blotting. Titanium plates demonstrated different surface microtopography. Parameter Ra values of SLA group were around 3.4 µm, which was higher than PT group. Exposure to the FSS of 12 dynes/cm2 significantly induced positive upregulation of cellular proliferation and the expression of FAK, which were directly correlated with the duration of exposure and surface. Cells in SLA group were able to endurance the longtime of FSS, especially under the FSS of 16 dynes/cm2. SLA surface had a positive influence on the expression of FAK. Different surface modifications created different microtopography of titanium plates. Cell proliferation and the mRNA and protein expression of FAK were stimulated by FSS and regulated by a marked synergistic effect of surface topography and the level and duration of FSS.
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Affiliation(s)
- Xin Lei
- Department of Stomatology, Shenzhen Longhua District Central Hospital, Shenzhen, China
| | - Qiong Liu
- Stomatological Hospital, Southern Medical University, Guangzhou Guangdong, China
| | - Shiyi Li
- Stomatological Hospital, Southern Medical University, Guangzhou Guangdong, China
| | - Zhaoqiang Zhang
- Stomatological Hospital, Southern Medical University, Guangzhou Guangdong, China
| | - Xiaoyu Yang
- Stomatological Hospital, Southern Medical University, Guangzhou Guangdong, China
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Shar JA, Keswani SG, Grande-Allen KJ, Sucosky P. Computational Assessment of Valvular Dysfunction in Discrete Subaortic Stenosis: A Parametric Study. Cardiovasc Eng Technol 2021; 12:559-575. [PMID: 33432514 DOI: 10.1007/s13239-020-00513-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Accepted: 12/22/2020] [Indexed: 01/16/2023]
Abstract
PURPOSE Discrete subaortic stenosis (DSS) is a left-ventricular outflow tract (LVOT) obstruction caused by a membranous lesion. DSS is associated with steep aortoseptal angles (AoSAs) and is a risk factor for aortic regurgitation (AR). However, the etiology of AR secondary to DSS remains unknown. This study aimed at quantifying computationally the impact of AoSA steepening and DSS on aortic valve (AV) hemodynamics and AR. METHODS An LV geometry reconstructed from cine-MRI data was connected to an AV geometry to generate a unified 2D LV-AV model. Six geometrical variants were considered: unobstructed (CTRL) and DSS-obstructed LVOT (DSS), each reflecting three AoSA variations (110°, 120°, 130°). Fluid-structure interaction simulations were run to compute LVOT flow, AV leaflet dynamics, and regurgitant fraction (RF). RESULTS AoSA steepening and DSS generated vortex dynamics alterations and stenotic flow conditions. While the CTRL-110° model generated the highest degree of leaflet opening asymmetry, DSS preferentially altered superior leaflet kinematics, and caused leaflet-dependent alterations in systolic fluttering. LVOT steepening and DSS subjected the leaflets to increasing WSS overloads (up to 94% increase in temporal shear magnitude), while DSS also increased WSS bidirectionality on the inferior leaflet belly (+ 0.30-point in oscillatory shear index). Although AoSA steepening and DSS increased diastolic transvalvular backflow, regurgitant fractions (RF < 7%) remained below the threshold defining clinical mild AR. CONCLUSIONS The mechanical interactions between AV leaflets and LVOT steepening/DSS hemodynamic derangements do not cause AR. However, the leaflet WSS abnormalities predicted in those anatomies provide new support to a mechanobiological etiology of AR secondary to DSS.
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Affiliation(s)
- Jason A Shar
- Department of Mechanical and Materials Engineering, Wright State University, Dayton, USA
| | - Sundeep G Keswani
- Division of Pediatric Surgery, Department of Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, USA
| | | | - Philippe Sucosky
- Department of Mechanical Engineering, Kennesaw State University, 840 Polytechnic Lane, Marietta, GA, 30060, USA.
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Yang P, Troncone L, Augur ZM, Kim SSJ, McNeil ME, Yu PB. The role of bone morphogenetic protein signaling in vascular calcification. Bone 2020; 141:115542. [PMID: 32736145 PMCID: PMC8185454 DOI: 10.1016/j.bone.2020.115542] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 07/02/2020] [Accepted: 07/04/2020] [Indexed: 01/10/2023]
Abstract
Vascular calcification is associated with atherosclerosis, chronic kidney disease, and diabetes, and results from processes resembling endochondral or intramembranous ossification, or from processes that are distinct from ossification. Bone morphogenetic proteins (BMP), as well as other ligands, receptors, and regulators of the transforming growth factor beta (TGFβ) family regulate vascular and valvular calcification by modulating the phenotypic plasticity of multipotent progenitor lineages associated with the vasculature or valves. While osteogenic ligands BMP2 and BMP4 appear to be both markers and drivers of vascular calcification, particularly in atherosclerosis, BMP7 may serve to protect against calcification in chronic kidney disease. BMP signaling regulators such as matrix Gla protein and BMP-binding endothelial regulator protein (BMPER) play protective roles in vascular calcification. The effects of BMP signaling molecules in vascular calcification are context-dependent, tissue-dependent, and cell-type specific. Here we review the current knowledge on mechanisms by which BMP signaling regulates vascular calcification and the potential therapeutic implications.
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Affiliation(s)
- Peiran Yang
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Luca Troncone
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Zachary M Augur
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Stephanie S J Kim
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Megan E McNeil
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Paul B Yu
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
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Shar JA, Brown KN, Keswani SG, Grande-Allen J, Sucosky P. Impact of Aortoseptal Angle Abnormalities and Discrete Subaortic Stenosis on Left-Ventricular Outflow Tract Hemodynamics: Preliminary Computational Assessment. Front Bioeng Biotechnol 2020; 8:114. [PMID: 32175314 PMCID: PMC7056880 DOI: 10.3389/fbioe.2020.00114] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 02/04/2020] [Indexed: 12/27/2022] Open
Abstract
Discrete subaortic stenosis (DSS) is an obstruction of the left ventricular outflow tract (LVOT) due to the formation of a fibromuscular membrane upstream of the aortic valve. DSS is a major risk factor for aortic regurgitation (AR), which often persists after surgical resection of the membrane. While the etiology of DSS and secondary AR is largely unknown, the frequent association between DSS and aortoseptal angle (AoSA) abnormalities has supported the emergence of a mechanobiological pathway by which hemodynamic stress alterations on the septal wall could trigger a biological cascade leading to fibrosis and membrane formation. The resulting LVOT flow disturbances could activate the valve endothelium and contribute to AR. In an effort to assess this hypothetical mechano-etiology, this study aimed at isolating computationally the effects of AoSA abnormalities on septal wall shear stress (WSS), and the impact of DSS on LVOT hemodynamics. Two-dimensional computational fluid dynamics models featuring a normal AoSA (N-LV), a steep AoSA (S-LV), and a steep AoSA with a DSS lesion (DSS-LV) were designed to compute the flow in patient-specific left ventricles (LVs). Boundary conditions consisted of transient velocity profiles at the mitral inlet and LVOT outlet, and patient-specific LV wall motion. The deformation of the DSS lesion was computed using a two-way fluid-structure interaction modeling strategy. Turbulence was accounted for via implementation of the k-ω turbulence model. While the N-LV and S-LV models generated similar LVOT flow characteristics, the DSS-LV model resulted in an asymmetric LVOT jet-like structure, subaortic stenotic conditions (up to 2.4-fold increase in peak velocity, 45% reduction in effective jet diameter vs. N-LV/S-LV), increased vorticity (2.8-fold increase) and turbulence (5- and 3-order-of-magnitude increase in turbulent kinetic energy and Reynolds shear stress, respectively). The steep AoSA subjected the septal wall to a 23% and 69% overload in temporal shear magnitude and gradient, respectively, without any substantial change in oscillatory shear index. This study reveals the existence of WSS overloads on septal wall regions prone to DSS lesion formation in steep LVOTs, and the development of highly turbulent, stenotic and asymmetric flow in DSS LVOTs, which support a possible mechano etiology for DSS and secondary AR.
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Affiliation(s)
- Jason A. Shar
- Department of Mechanical and Materials Engineering, Wright State University, Dayton, OH, United States
| | - Kathleen N. Brown
- Department of Bioengineering, Rice University, Houston, TX, United States
| | - Sundeep G. Keswani
- Division of Pediatric Surgery, Texas Children’s Hospital, Houston, TX, United States
- Department of Surgery, Baylor College of Medicine, Houston, TX, United States
| | - Jane Grande-Allen
- Department of Bioengineering, Rice University, Houston, TX, United States
| | - Philippe Sucosky
- Department of Mechanical and Materials Engineering, Wright State University, Dayton, OH, United States
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Liu J, Cornelius K, Graham M, Leonard T, Tipton A, Yorde A, Sucosky P. Design and Computational Validation of a Novel Bioreactor for Conditioning Vascular Tissue to Time-Varying Multidirectional Fluid Shear Stress. Cardiovasc Eng Technol 2019; 10:531-542. [PMID: 31309526 DOI: 10.1007/s13239-019-00426-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Accepted: 07/04/2019] [Indexed: 12/31/2022]
Abstract
PURPOSE The cardiovascular endothelium experiences pulsatile and multidirectional fluid wall shear stress (WSS). While the effects of non-physiologic WSS magnitude and pulsatility on cardiovascular function have been studied extensively, the impact of directional abnormalities remains unknown due to the challenge to replicate this characteristic in vitro. To address this gap, this study aimed at designing a bioreactor capable of subjecting cardiovascular tissue to time-varying WSS magnitude and directionality. METHODS The device consisted of a modified cone-and-plate bioreactor. The cone rotation generates a fluid flow subjecting tissue to desired WSS magnitude, while WSS directionality is achieved by altering the alignment of the tissue relative to the flow at each instant of time. Computational fluid dynamics was used to verify the device ability to replicate the native WSS of the proximal aorta. Cone and tissue mount velocities were determined using an iterative optimization procedure. RESULTS Using conditions derived from cone-and-plate theory, the initial simulations yielded root-mean-square errors of 22.8 and 8.4% in WSS magnitude and angle, respectively, between the predicted and the target signals over one cycle, relative to the time-averaged target values. The conditions obtained after two optimization iterations reduced those errors to 3.5 and 0.5%, respectively, and generated 0.2% and 0.01% difference in time-averaged WSS magnitude and angle, respectively, relative to the target waveforms. CONCLUSIONS A bioreactor capable of generating simultaneously desired time-varying WSS magnitude and directionality was designed and validated computationally. The ability to subject tissue to in vivo-like WSS will provide new insights into cardiovascular mechanobiology and disease.
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Affiliation(s)
- Janet Liu
- Department of Mechanical and Materials Engineering, Wright State University, 257 Russ Engineering Center, Dayton, OH, 45435, USA
| | - Kurtis Cornelius
- Department of Mechanical and Materials Engineering, Wright State University, 257 Russ Engineering Center, Dayton, OH, 45435, USA
| | - Mathew Graham
- Department of Mechanical and Materials Engineering, Wright State University, 257 Russ Engineering Center, Dayton, OH, 45435, USA
| | - Tremayne Leonard
- Department of Mechanical and Materials Engineering, Wright State University, 257 Russ Engineering Center, Dayton, OH, 45435, USA
| | - Austin Tipton
- Department of Mechanical and Materials Engineering, Wright State University, 257 Russ Engineering Center, Dayton, OH, 45435, USA
| | - Abram Yorde
- Department of Mechanical and Materials Engineering, Wright State University, 257 Russ Engineering Center, Dayton, OH, 45435, USA
| | - Philippe Sucosky
- Department of Mechanical and Materials Engineering, Wright State University, 257 Russ Engineering Center, Dayton, OH, 45435, USA.
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Massé DD, Shar JA, Brown KN, Keswani SG, Grande-Allen KJ, Sucosky P. Discrete Subaortic Stenosis: Perspective Roadmap to a Complex Disease. Front Cardiovasc Med 2018; 5:122. [PMID: 30320123 PMCID: PMC6166095 DOI: 10.3389/fcvm.2018.00122] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 08/17/2018] [Indexed: 12/13/2022] Open
Abstract
Discrete subaortic stenosis (DSS) is a congenital heart disease that results in the formation of a fibro-membranous tissue, causing an increased pressure gradient in the left ventricular outflow tract (LVOT). While surgical resection of the membrane has shown some success in eliminating the obstruction, it poses significant risks associated with anesthesia, sternotomy, and heart bypass, and it remains associated with a high rate of recurrence. Although a genetic etiology had been initially proposed, the association between DSS and left ventricle (LV) geometrical abnormalities has provided more support to a hemodynamic etiology by which congenital or post-surgical LVOT geometric derangements could generate abnormal shear forces on the septal wall, triggering in turn a fibrotic response. Validating this hypothetical etiology and understanding the mechanobiological processes by which altered shear forces induce fibrosis in the LVOT are major knowledge gaps. This perspective paper describes the current state of knowledge of DSS, articulates the research needs to yield mechanistic insights into a significant pathologic process that is poorly understood, and proposes several strategies aimed at elucidating the potential mechanobiological synergies responsible for DSS pathogenesis. The proposed roadmap has the potential to improve DSS management by identifying early targets for prevention of the fibrotic lesion, and may also prove beneficial in other fibrotic cardiovascular diseases associated with altered flow.
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Affiliation(s)
- Danielle D Massé
- Department of Mechanical and Materials Engineering, Wright State University, Dayton, OH, United States
| | - Jason A Shar
- Department of Mechanical and Materials Engineering, Wright State University, Dayton, OH, United States
| | - Kathleen N Brown
- Department of Bioengineering, Rice University, Houston, TX, United States
| | - Sundeep G Keswani
- Division of Pediatric Surgery, Texas Children's Hospital, Houston, TX, United States.,Department of Surgery, Baylor College of Medicine, Houston, TX, United States
| | | | - Philippe Sucosky
- Department of Mechanical and Materials Engineering, Wright State University, Dayton, OH, United States
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8
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Cao K, Sucosky P. Computational comparison of regional stress and deformation characteristics in tricuspid and bicuspid aortic valve leaflets. INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING 2017; 33:e02798. [PMID: 27138991 DOI: 10.1002/cnm.2798] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2015] [Revised: 03/22/2016] [Accepted: 04/20/2016] [Indexed: 06/05/2023]
Abstract
The bicuspid aortic valve (BAV) is the most common congenital valvular defect and a major risk factor for secondary calcific aortic valve disease. While hemodynamics is presumed to be a potential contributor to this complication, the validation of this theory has been hampered by the limited knowledge of the mechanical stress abnormalities experienced by BAV leaflets and their dependence on the heterogeneous BAV fusion patterns. The objective of this study was to compare computationally the regional and temporal fluid wall shear stress (WSS) and structural deformation characteristics in tricuspid aortic valve (TAV), type-0, and type-I BAV leaflets. Arbitrary Lagrangian-Eulerian fluid-structure interaction models were designed to simulate the flow and leaflet dynamics in idealized TAV, type-0, and type-I BAV geometries subjected to physiologic transvalvular pressure. The regional leaflet mechanics was quantified in terms of temporal shear magnitude (TSM), oscillatory shear index (OSI), temporal shear gradient (TSG), and stretch. The simulations identified regions of WSS overloads and increased WSS bidirectionality (174% increase in temporal shear magnitude, 0.10 increase in OSI on type-0 leaflets) in BAV leaflets relative to TAV leaflets. BAV leaflets also experienced larger radial deformations than TAV leaflets (4% increase in type-0 BAV leaflets). Type-I BAV leaflets exhibited contrasted WSS environments marked by WSS overloads on the non-coronary leaflet and sub-physiologic WSS levels on the fused leaflet. This study provides important insights into the mechanical characteristics of BAV leaflets, which may further our understanding of the role played by hemodynamic forces in BAV disease. Copyright © 2016 John Wiley & Sons, Ltd.
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Affiliation(s)
- K Cao
- Department of Aerospace and Mechanical Engineering, University of Notre Dame, 365 Fitzpatrick Hall, Notre Dame, IN, 46556, USA
| | - P Sucosky
- Department of Mechanical and Materials Engineering, Wright State University, 3640 Colonel Glenn Highway, Dayton, OH, 45435, USA
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Atkins SK, McNally A, Sucosky P. Mechanobiology in Cardiovascular Disease Management: Potential Strategies and Current Needs. Front Bioeng Biotechnol 2016; 4:79. [PMID: 27777927 PMCID: PMC5056184 DOI: 10.3389/fbioe.2016.00079] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2016] [Accepted: 09/26/2016] [Indexed: 01/17/2023] Open
Affiliation(s)
- Samantha K Atkins
- Department of Aerospace and Mechanical Engineering, University of Notre Dame , Notre Dame, IN , USA
| | - Andrew McNally
- Department of Aerospace and Mechanical Engineering, University of Notre Dame , Notre Dame, IN , USA
| | - Philippe Sucosky
- Department of Materials and Mechanical Engineering, Wright State University , Dayton, OH , USA
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Cao K, Sucosky P. Aortic valve leaflet wall shear stress characterization revisited: impact of coronary flow. Comput Methods Biomech Biomed Engin 2016; 20:468-470. [PMID: 27712083 DOI: 10.1080/10255842.2016.1244266] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Computational characterizations of aortic valve hemodynamics have typically discarded the effects of coronary flow. The objective of this study was to complement our previous fluid-structure interaction aortic valve model with a physiologic coronary circulation model to quantify the impact of coronary flow on aortic sinus hemodynamics and leaflet wall shear stress (WSS). Coronary flow suppressed vortex development in the two coronary sinuses and altered WSS magnitude and directionality on the three leaflets, with the most substantial differences occurring in the belly and tip regions.
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Affiliation(s)
- K Cao
- a Department of Aerospace and Mechanical Engineering , University of Notre Dame , Notre Dame , IN , USA
| | - P Sucosky
- b Department of Mechanical and Materials Engineering , Wright State University , Dayton , OH , USA
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Atkins SK, Moore AN, Sucosky P. Bicuspid aortic valve hemodynamics does not promote remodeling in porcine aortic wall concavity. World J Cardiol 2016; 8:89-97. [PMID: 26839660 PMCID: PMC4728110 DOI: 10.4330/wjc.v8.i1.89] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2015] [Revised: 10/30/2015] [Accepted: 12/04/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the role of type-I left-right bicuspid aortic valve (LR-BAV) hemodynamic stresses in the remodeling of the thoracic ascending aorta (AA) concavity, in the absence of underlying genetic or structural defects.
METHODS: Transient wall shear stress (WSS) profiles in the concavity of tricuspid aortic valve (TAV) and LR-BAV AAs were obtained computationally. Tissue specimens excised from the concavity of normal (non-dilated) porcine AAs were subjected for 48 h to those stress environments using a shear stress bioreactor. Tissue remodeling was characterized in terms of matrix metalloproteinase (MMP) expression and activity via immunostaining and gelatin zymography.
RESULTS: Immunostaining semi-quantification results indicated no significant difference in MMP-2 and MMP-9 expression between the tissue groups exposed to TAV and LR-BAV AA WSS (P = 0.80 and P = 0.19, respectively). Zymography densitometry revealed no difference in MMP-2 activity (total activity, active form and latent form) between the groups subjected to TAV AA and LR-BAV AA WSS (P = 0.08, P = 0.15 and P = 0.59, respectively).
CONCLUSION: The hemodynamic stress environment present in the concavity of type-I LR-BAV AA does not cause any significant change in proteolytic enzyme expression and activity as compared to that present in the TAV AA.
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