Binding of Pentagalloyl Glucose to Aortic Wall Proteins: Insights from Peptide Mapping and Simulated Docking Studies.

Pentagalloyl glucose (PGG) is currently being investigated as a non-surgical treatment for abdominal aortic aneurysms (AAAs); however, the molecular mechanisms of action of PGG on the AAA matrix components and the intra-luminal thrombus (ILT) still need to be better understood. To assess these interactions, we utilized peptide fingerprinting and molecular docking simulations to predict the binding of PGG to vascular proteins in normal and aneurysmal aorta, including matrix metalloproteinases (MMPs), cytokines, and fibrin. We performed PGG diffusion studies in pure fibrin gels and human ILT samples.

Pentagalloyl glucose-stabilized decellularized bovine jugular vein valved conduits as pulmonary conduit replacement.

Congenital heart diseases (CHD) are one of the most frequently diagnosed congenital disorders, affecting approximately 40,000 live births annually in the United States. Out of the new patients diagnosed with CHD yearly, an estimated 2,500 patients require a substitute, non-native conduit artery to replace structures congenitally absent or hypoplastic. Devices used for conduit replacement encounter limitations exhibiting varying degrees of stiffness, calcification, susceptibility to infection, thrombosis, and a lack of implant growth capacity.

Structural and biomechanical characterizations of acellular porcine mitral valve scaffolds: anterior leaflets, posterior leaflets, and chordae tendineae.

Mitral valve (MV) tissue engineering is still in its early stage, and one major challenge in MV tissue engineering is to identify appropriate scaffold materials. With the potential of acellular MV scaffolds being demonstrated recently, it is important to have a full understanding of the biomechanics of the native MV components and their acellular scaffolds. In this study, we have successfully characterized the structural and mechanical properties of porcine MV components, including anterior leaflet (AL), posterior leaflet (PL), strut chordae, and basal chordae, before and after decellularization.

VLA4-Enhanced Allogeneic Endothelial Progenitor Cell-Based Therapy Preserves the Aortic Valve Function in a Mouse Model of Dyslipidemia and Diabetes.

The number and function of endothelial progenitor cells (EPCs) are reduced in diabetes, contributing to deteriorated vascular repair and the occurrence of cardiovascular complications. Here, we present the results of treating early diabetic dyslipidemic mice or dyslipidemic with disease-matched EPCs modified to overexpress VLA4 (VLA4-EPCs) as compared with the treatment of EPCs transfected with GFP (GFP-EPCs) as well as EPCs from healthy animals. Organ imaging of injected PKH26-stained cells showed little pulmonary first-pass effects and distribution in highly vascularized organs, with splenic removal from circulation, mostly in non-diabetic animals.

Aortic valve disease in diabetes: Molecular mechanisms and novel therapies.

Valve disease and particularly calcific aortic valve disease (CAVD) and diabetes (DM) are progressive diseases constituting a global health burden for all aging societies (Progress in Cardiovascular Diseases. 2014;56(6):565: Circulation Research. 2021;128(9):1344).

Preclinical Testing of Living Tissue-Engineered Heart Valves for Pediatric Patients, Challenges and Opportunities.

Pediatric patients with cardiac congenital diseases require heart valve implants that can grow with their natural somatic increase in size. Current artificial valves perform poorly in children and cannot grow; thus, living-tissue-engineered valves capable of sustaining matrix homeostasis could overcome the current drawbacks of artificial prostheses and minimize the need for repeat surgeries. To prepare living-tissue-engineered valves, we produced completely acellular ovine pulmonary valves by perfusion.

High Glucose Induced Changes in Human VEC Phenotype in a 3D Hydrogel Derived From Cell-Free Native Aortic Root.

Valvular endothelial cells (VEC) have key roles in maintaining valvular integrity and homeostasis, and dysfunctional VEC are the initiators and major contributors to aortic valve disease in diabetes. Previous studies have shown that HG stimulated an inflammatory phenotype in VEC. Inflammation was shown to induce endothelial to mesenchymal transition (EndMT), a process extensively involved in many pathologies, including calcification of the aortic valve.

Challenges in Perioperative Animal Care for Orthotopic Implantation of Tissue-Engineered Pulmonary Valves in the Ovine Model.

Background: Development of valvular substitutes meeting the performance criteria for surgical correction of congenital heart malformations is a major research challenge. The sheep is probably the most widely used animal model in heart valves regenerative medicine. Although the standard cardiopulmonary bypass (CPB) technique and various anesthetic and surgical protocols are reported to be feasible and safe, they are associated with significant morbidity and mortality rates.

Integrins α4β1 and αVβ3 are Reduced in Endothelial Progenitor Cells from Diabetic Dyslipidemic Mice and May Represent New Targets for Therapy in Aortic Valve Disease.

Diabetes reduces the number and induces dysfunction in circulating endothelial progenitor cells (EPCs) by mechanisms that are still uncovered. This study aims to evaluate the number, viability, phenotype, and function of EPCs in dyslipidemic mice with early diabetes mellitus and EPC infiltration in the aortic valve in order to identify possible therapeutic targets in diabetes-associated cardiovascular disease. A streptozotocin-induced diabetic apolipoprotein E knock-out ApoE) mouse model was used to identify the early and progressive changes, at 4 or 7 days on atherogenic diet after the last streptozotocin or citrate buffer injection.

Chemical stabilization of the extracellular matrix attenuates growth of experimentally induced abdominal aorta aneurysms in a large animal model.

Objective: The goal of the present study was to test the safety and efficacy of chemical stabilization of the arterial extracellular matrix as a novel nonoperative treatment of abdominal aortic aneurysms (AAAs) in a clinically relevant large animal model.

Methods: To achieve matrix stabilization, we used 1,2,3,4,6-pentagalloylglucose (PGG), a noncytotoxic polyphenolic agent capable of binding to and stabilizing elastin and collagen against the action of degrading enzymes. We first optimized the therapeutic PGG formulation and time of exposure by in vitro testing on porcine aortas using phenol histologic staining with iron chloride, elastic recoil assays, and PGG quantification as a function of tissue thickness.

Transcatheter mitral valve replacement (TMVR): annular or apical fixation?

Aims: The aim of this study was to evaluate the impact of two different transcatheter mitral valve replacement (TMVR) fixation strategies on the neo left ventricular outflow tract (neo-LVOT) and aorto-mitral angulation (AMA) after TMVR.

Methods And Results: Two different self-expanding nitinol valved stents were developed for transapical TMVR. In one group, the stents were fixed with an annular fixation system (ANN group, n=6).

Diabetes-induced early molecular and functional changes in aortic heart valves in a murine model of atherosclerosis.

Diabetes contributes directly to the development of cardiovascular aortic valve disease. There is currently no drug therapy available for a dysfunctional valve and this urges the need for additional research to identify distinctive mechanisms of cardiovascular aortic valve disease evolution. The aim of this study was to evaluate changes of valvular aortic lesions induced in a hyperlipemic ApoE mouse model by early type 1 diabetes onset (at 4 and 7 days after streptozotocin induction).

Pentagalloyl Glucose and Its Functional Role in Vascular Health: Biomechanics and Drug-Delivery Characteristics.

Pentagalloyl glucose (PGG) is an elastin-stabilizing polyphenolic compound that has significant biomedical benefits, such as being a free radical sink, an anti-inflammatory agent, anti-diabetic agent, enzymatic resistant properties, etc. This review article focuses on the important benefits of PGG on vascular health, including its role in tissue mechanics, the different modes of pharmacological administration (e.g.

The Effect of Pentagalloyl Glucose on the Wall Mechanics and Inflammatory Activity of Rat Abdominal Aortic Aneurysms.

An abdominal aortic aneurysm (AAA) is a permanent localized expansion of the abdominal aorta with mortality rate of up to 90% after rupture. AAA growth is a process of vascular degeneration accompanied by a reduction in wall strength and an increase in inflammatory activity. It is unclear whether this process can be intervened to attenuate AAA growth, and hence, it is of great clinical interest to develop a technique that can stabilize the AAA.

Detergent-based decellularization strategy preserves macro- and microstructure of heart valves.

Objectives: Biological tissue has great potential to function as bioprostheses in patients for heart valve replacement. As these matrices are mainly xenogenic, the immunogenicity needs to be reduced by decellularization steps. Reseeding of bioscaffolds has tremendous potential to prevent calcification upon implantation, so intact microstructure of the material is mandatory.

Longitudinal Stretching for Maturation of Vascular Tissues Using Magnetic Forces.

Cellular spheroids were studied to determine their use as "bioinks" in the biofabrication of tissue engineered constructs. Specifically, magnetic forces were used to mediate the cyclic longitudinal stretching of tissues composed of Janus magnetic cellular spheroids (JMCSs), as part of a post-processing method for enhancing the deposition and mechanical properties of an extracellular matrix (ECM). The purpose was to accelerate the conventional tissue maturation process via novel post-processing techniques that accelerate the functional, structural, and mechanical mimicking of native tissues.

Iron Oxide Nanoparticles Stimulates Extra-Cellular Matrix Production in Cellular Spheroids.

Nanotechnologies have been integrated into drug delivery, and non-invasive imaging applications, into nanostructured scaffolds for the manipulation of cells. The objective of this work was to determine how the physico-chemical properties of magnetic nanoparticles (MNPs) and their spatial distribution into cellular spheroids stimulated cells to produce an extracellular matrix (ECM). The MNP concentration (0.

A Standardized Dissection Protocol to Generate Aortic Valvular Scaffolds from Porcine Hearts.

Objective: To describe a particular harvesting procedure for isolating intact porcine aortic heart valve roots as potential sources for biologic scaffolds.

Methods: Fresh porcine hearts were brought to the Tissue Engineering and Regenerative Medicine Laboratory at the University of Medicine and Pharmacy in Targu Mures. The aortic roots were extracted from the porcine hearts by anatomical dissection.

Immunomodulatory effects of adipose tissue-derived stem cells on elastin scaffold remodeling in diabetes.

Diabetes is a major risk factor for the progression of vascular disease, contributing to elevated levels of glycoxidation, chronic inflammation and calcification. Tissue engineering emerges as a potential solution for the treatment of vascular diseases however there is a considerable gap in the understanding of how scaffolds and stem cells will perform in patients with diabetes. We hypothesized that adipose tissue-derived stem cells (ASCs) by virtue of their immunosuppressive potential would moderate the diabetes-intensified inflammatory reactions and induce positive construct remodeling.

Bioreactor Conditioning of Valve Scaffolds Seeded Internally with Adult Stem Cells.

The goal of this study was to test the hypothesis that stem cells, as a response to valve-specific extracellular matrix "niches" and mechanical stimuli, would differentiate into valvular interstitial cells (VICs). Porcine aortic root scaffolds were prepared by decellularization. After verifying that roots exhibited adequate hemodynamics , we seeded human adipose-derived stem cells (hADSCs) within the interstitium of the cusps and subjected the valves to pulsatile bioreactor testing in pulmonary pressures and flow conditions.

Stabilized Collagen and Elastin-Based Scaffolds for Mitral Valve Tissue Engineering.

There is a significant clinical need for new approaches to treatment of mitral valve disease. The aim of this study was to develop a tissue-engineered mitral valve scaffold possessing appropriate composition and structure to ensure ideal characteristics of mitral valves, such as large orifice, rapid opening and closure, maintenance of mitral annulus-papillary muscle continuity, in vivo biocompatibility and extended durability. An extracellular matrix-based scaffold was generated, based on the native porcine mitral valve as starting material and a technique for porcine cell removal without causing damage to the matrix components.

Interobserver variability in physician-modified endograft planning by comparison with a three-dimensional printed aortic model.

Background: With the increasing application of fenestrated and physician-modified endografting for aneurysm repair, there is increasing concern about the accuracy of vessel position measurements based on computed tomography scans. Inaccuracies in measurements may result in a "window-shutter" or "eclipsing" phenomenon whereby the fenestration may not overlie the vessel ostium completely. We hypothesized that vessel position measurements from reconstructed imaging do not represent the true vessel position as obtained from a three-dimensional (3D) printed physical model of the visceral aortic segment.