elastin and epigallocatechin-gallate

Tissue engineered vascular grafts possess several advantages over synthetic or autologous grafts, including increased availability and reduced rates of infection and thrombosis. Engineered grafts constructed from human induced pluripotent stem cell derivatives further offer enhanced reproducibility in graft production. One notable obstacle to clinical application of these grafts is the lack of elastin in the vessel wall, which would serve to endow compliance in addition to mechanical strength. This study establishes the ability of the polyphenol compound epigallocatechin gallate, a principal component of green tea, to facilitate the extracellular formation of elastin fibers in vascular smooth muscle cells derived from human induced pluripotent stem cells. Further, this study describes the creation of a doxycycline-inducible elastin expression system to uncouple elastin production from vascular smooth muscle cell proliferative capacity to permit fiber formation in conditions conducive to robust tissue engineering.

Topics: Catechin; Elastin; Humans; Induced Pluripotent Stem Cells; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Reproducibility of Results; Tissue Engineering

The lifetime of bioprosthetic heart valves (BHVs) is limited by the mechanical damage and calcification. The major components of BHVs are collagen and elastin. Collagen could be well protected by glutaraldehyde (GLUT) crosslinking, while elastin is not stabilized and has a high risk of degradation, which could lead to the calcification of BHVs. We aimed to develop methods for stabilizing elastin and decreasing calcification. We investigated the combined tannic acid (TA) or epigallocatechin gallate (EGCG) with ferric chloride to stabilize elastin and prevent calcification. We found that the amount of TA/EGCG bound to elastin was in a time-dependent pattern and this reaction showed better efficiency in acidic condition and ethanol-water mixed solvents. Moreover, Fe

Topics: Animals; Bioprosthesis; Calcinosis; Catechin; Chlorides; Collagen; Cross-Linking Reagents; Elastin; Ferric Compounds; Glutaral; Heart Valve Prosthesis; Male; Pericardium; Polyphenols; Protein Stability; Rats, Sprague-Dawley; Swine; Tannins; Tensile Strength

Valvular heart diseases lead to over 300,000 heart valve replacements worldwide each year. Commercially available bioprosthetic heart valves (BHVs) are mostly made from porcine or bovine pericardiums which were crosslinked by glutaraldehyde (GLUT). However, valve failures can occur within 10 years due to progressive degradation and calcification. GLUT could crosslink collagen but it fails to stabilize elastin. In this current study, we developed a new BHVs preparation strategy named as "GLUT/TE/LOXL/EGCG" that utilizes exogenous tropoelastin (TE)/lysyl oxidase (LOXL) and epigallocatechin gallate (EGCG) to increase the elastin content as well as the stabilization of elastin. The feeding ratios of tropoelastin and lysyl oxidase were optimized. The contents of desmosine and insoluble elastin, biomechanics, cytotoxicity, hemocompatibility, in vivo componential stability and anti-calcification potential were characterized. Pericardiums with increased elastin content had improved the mechanical properties. GLUT/TE/LOXL/EGCG-treated pericardiums had similar cytotoxicity and coagulation properties compared to GLUT and GLUT/EGCG control. We demonstrated that GLUT/TE/LOXL/EGCG-treated pericardiums had high amount of insoluble elastin in 90 days' rat subdermal implantation model, and better resistance for calcification. This new tropoelastin and lysyl oxidase treatments strategy would be a promising method to make BHVs which have better structural stability and anti-calcification properties.

Topics: Animals; Biomechanical Phenomena; Bioprosthesis; Calcinosis; Catechin; Cross-Linking Reagents; Elastin; Glutaral; Heart Valve Prosthesis; Male; Pericardium; Protein Stability; Protein-Lysine 6-Oxidase; Rats, Sprague-Dawley; Swine; Tropoelastin

Inflammation-mediated elastin destruction in the aortic medial layer is related to progression of abdominal aortic aneurysm (AAA). Epigallocatechin-3-gallate (EGCG), a major component of green tea polyphenols, reportedly increases elastin synthesis in vitro and may possess anti-inflammatory effects. We used a rat model to investigate whether EGCG could prevent AAA progression.. The abdominal aortic diameter was significantly smaller in the EGCG group than in the control group on day 28 (2.9 ± 0.2 vs 2.3 ± 0.1 mm; P < .0001). The medial layer wall thickness and elastin content were significantly greater in the EGCG group than in the control group on day 28 (68.4 ± 13.6 vs 46.7 ± 13.4 μm [P < .001] and 20.3 ± 4.6 vs 9.5 ± 3.6% [P < .0001], respectively). Gene expression levels of tropoelastin and lysyl oxidase were significantly higher in the EGCG group immediately before AAA induction, indicating promoted elastoregeneration by EGCG administration (tropoelastin: 0.59 ± 0.36 control vs 1.24 ± 0.36 EGCG [P < .05], lysyl oxidase: 0.77 ± 0.45 control vs 1.34 ± 0.4 EGCG [P < .05]) (fold increase). Gene expression levels of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, were significantly downregulated in the EGCG group (1.82 ± 0.71 vs 0.97 ± 0.59 [P < .05] and 3.91 ± 3.24 vs 0.89 ± 0.59 [P < .05], respectively). On day 7, gene expression levels and gelatinolytic activity of matrix metalloproteinase 9 were significantly lower in the EGCG group (1.41 ± 0.86 vs 0.51 ± 0.42 [P < .05] and 1.00 ± 0.17 vs 0.29 ± 0.12 [P < .0001], respectively), whereas gene expression levels of tissue inhibitors of metalloproteinase-1 were significantly higher in the EGCG group (0.96 ± 0.11 vs 1.14 ± 0.09; P < .05).. EGCG attenuated AAA progression in a rat model by preserving the aortic thickness and elastin content of the medial layer through regeneration of elastin, as mediated by anti-inflammatory effects, and subsequent reduction of matrix metalloproteinase activity.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Calcium Chloride; Catechin; Collagen; Cytokines; Dilatation, Pathologic; Disease Models, Animal; Disease Progression; Elastin; Gene Expression Regulation; Inflammation Mediators; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 9; Pancreatic Elastase; Phytotherapy; Plant Extracts; Plants, Medicinal; Polyphenols; Protein-Lysine 6-Oxidase; Rats, Sprague-Dawley; Tea; Time Factors; Tropoelastin

Abdominal aortic aneurysms (AAA) are progressive dilatations of infra-renal aorta causing structural weakening rendering the aorta prone to rupture. AAA can be potentially stabilized by inhibiting inflammatory enzymes such as matrix metalloproteinases (MMP); however, active regression of AAA is not possible without new elastic fiber regeneration. Here we report the elastogenic benefit of direct delivery of polyphenols such as pentagalloyl glucose (PGG), epigallocatechin gallate (EGCG), and catechin, to smooth muscle cells obtained either from healthy or from aneurysmal rat aorta. Addition of 10 μg/ml PGG and ECGC induce elastin synthesis, organization, and crosslinking while catechin does not. Our results indicate that polyphenols bind to monomeric tropoelastin and enhance coacervation, aid in crosslinking of elastin by increasing lysyl oxidase (LOX) synthesis, and by blocking MMP-2 activity. Thus, polyphenol treatments leads to increased mature elastin fibers synthesis without increasing the production of intracellular tropoelastin.

Topics: Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Catechin; Cells, Cultured; Elastic Tissue; Elastin; Fibrillins; Hydrolyzable Tannins; Kinetics; Male; Matrix Metalloproteinase 2; Microfilament Proteins; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Polyphenols; Protein-Lysine 6-Oxidase; Rats; Rats, Sprague-Dawley; Regeneration; Tropoelastin