Expression of tissue inhibitors of metalloproteinases type 1 and type 2 in the leaflets of explanted bioprosthetic heart valves: a new pathogenetic parallel between structural valve degeneration and calcific aortic stenosis

Objective: to study cellular and lipid infiltration, as well as the expression of tissue inhibitors of metalloproteinases (TIMP) types 1 and 2 in biological prosthetic heart valves (BPHVs) explanted due to dysfunction.Material and Methods. We examined 17 leaflets from 6 BPHVs, dissected from the aortic and mitral positions during valve replacement. For microscopic analysis, fragments of the BPHV leaflets were frozen and serial sections were made using a cryotome. In order to study cellular infiltration and the degree of degenerative changes in the prosthetic biomaterial, the sections were stained with Gill’s hematoxylin and eosin; Oil Red O stain was used to assess lipid deposition. Immunohistochemistry was used for cell typing and detection of TIMP-1/-2. The stained samples were analyzed by light microscopy.Results. Cellular and lipid infiltration of xenogeneic tissues was detected in all BPHV flaps studied. Recipient cells coexpressed pan-leukocyte and macrophage markers PTPRC/CD45 and CD68. Positive staining for TIMP-1/-2 co-localized with cell clusters but was absent in acellular sections.Conclusion. Cells infiltrating xenogeneic BPHV tissues express TIMP-1/-2. This suggests that BPHV immune rejection pathophysiology is partially similar to that of calcific aortic stenosis.

Download Full-text

Percutaneous implantation of prosthetic heart valves: From animal model to first human implantation in calcific aortic stenosis

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(03)82753-5 ◽

2003 ◽

Vol 41 (6) ◽

pp. 508 ◽

Cited By ~ 4

Author(s):

Alain Cribier ◽

Helene Eltchaninoff ◽

Christophe Tron ◽

Fabrice Bauer ◽

Genevieve Derumeaux ◽

...

Keyword(s):

Animal Model ◽

Aortic Stenosis ◽

Heart Valves ◽

Prosthetic Heart Valves ◽

Calcific Aortic Stenosis ◽

Human Implantation

Download Full-text

Bioprosthetic Heart Valves: Impact of Implantation on Biomaterials

ISRN Biomaterials ◽

10.5402/2013/728791 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 43

Author(s):

Pooja Singhal ◽

Adriana Luk ◽

Jagdish Butany

Keyword(s):

Heart Disease ◽

Heart Valves ◽

Prosthetic Heart Valves ◽

Bioprosthetic Heart Valves ◽

Modes Of Failure ◽

Mechanical Valves ◽

Different Types ◽

Patient Groups ◽

Bioprosthetic Valves

Prosthetic heart valves are commonly used in the treatment of valvular heart disease. Mechanical valves are more durable than the bioprosthetic valves; however, the need for long-term anticoagulant therapy renders them unsuitable for some patient groups. In this paper we discuss the different types and models of bioprosthesis, and in particular, pericardial bioprosthesis. We also discuss the preimplantation preparation processes, as well as their postimplantation changes and modes of failure.

Download Full-text

TExpression of matrix metalloproteinases 1, 2, 9, 12 in xenogenic tissues of epoxy-crosslinked bioprosthetic heart valves explanted due to dysfunction

Russian Journal of Cardiology ◽

10.15829/1560-4071-2020-3978 ◽

2020 ◽

Vol 25 (10) ◽

pp. 3978

Author(s):

A. E. Kostyunin ◽

T. V. Glushkova

Keyword(s):

Matrix Metalloproteinases ◽

Heart Valves ◽

Immune Cell ◽

Blood Clot ◽

Expression Patterns ◽

Bioprosthetic Valve ◽

Positive Staining ◽

Intense Staining ◽

Bioprosthetic Heart Valves ◽

Microscopic Studies

Aim. To study the expression patterns of matrix metalloproteinases (MMPs) -1, -2, -9, -12 in the leaflets of the epoxy-treated bioprostheses explanted due to dysfunction and to identify the pathways for the accumulation of these enzymes in the xenogenic tissues.Methods. 19 leaflets from seven epoxy-treated bioprostheses (Kemcor (n = 2), PeriCor (n = 2), UniLine (n = 2) and TiAra (n = 1)) explanted from the mitral or aortic positions during repeat heart valve replacements were included in a study. Sections for microscopic studies were cut on a standard rotary microtome. Cell typing and the expression of MMP-1, -2, -9, -12 were evaluated using immunohistochemical staining with the antibodies against PTPRC/CD45, CD68, neutrophil myeloperoxidase and the corresponding MMPs. Stained samples were examined by light microscopy.Results. Sporadic cell infiltrates, mainly composed of macrophages (PTPRC/CD45+, CD68+), were found in 17 leaflets from six explanted bioprostheses. Positive staining for MMP-1, -2, -9, -12 was colocalized with immune cell infiltrates. It is worth noting that MMP-9 staining was visualized even in the absence of cell infiltration, while more intense staining was found in the areas with a loose extracellular matrix. There were no signs of macrophage infiltration or MMP expression in xenotissues of pericardial bioprostheses failed due to thrombosis and explanted two days after implantation. However, a blood clot formed on its surface showed intense MMP-9 staining and included a large proportion of neutrophils positive for myeloperoxidase.Conclusion. Macrophages and other immune cells that infiltrate xenotissues of epoxy-treated bioprostheses are sources of MMP-1, -2, -9, -12. In addition, MMP-9 can diffuse into bioprosthetic valve leaflets from blood plasma of patients. Thus, MMPs deposition in xenotissues may contribute to the leaflet ruptures and calcifications leading to the development of bioprosthetic valve dysfunction.

Download Full-text

906 Differential expression of receptor activator of nuclear factor kappa B ligand and osteoprotegerin in calcific aortic stenosis

European Heart Journal ◽

10.1016/s0195-668x(03)94208-4 ◽

2003 ◽

Vol 24 (5) ◽

pp. 149

Author(s):

J KADEN

Keyword(s):

Aortic Stenosis ◽

Differential Expression ◽

Nuclear Factor Kappa B ◽

Nuclear Factor ◽

Calcific Aortic Stenosis ◽

Nuclear Factor Kappa ◽

Receptor Activator

Download Full-text

904 Aortic valve calcification is influenced by gender and associated with polymorphisms of the interleukin 10 and ccr5 gene in patients with degenerative calcific aortic stenosis

European Heart Journal ◽

10.1016/s0195-668x(03)94206-0 ◽

2003 ◽

Vol 24 (5) ◽

pp. 149

Author(s):

J ORTLEPP

Keyword(s):

Aortic Valve ◽

Aortic Stenosis ◽

Interleukin 10 ◽

Aortic Valve Calcification ◽

Ccr5 Gene ◽

Calcific Aortic Stenosis ◽

Valve Calcification

Download Full-text

Thrombosis of Surgical Bioprosthetic Heart Valves-Insights from Reports to International Medical Device Vigilance Systems

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0037-1598875 ◽

2017 ◽

Vol 65 (S 01) ◽

pp. S1-S110

Author(s):

C. Gestrich ◽

J.E. Klein ◽

B. Toctam ◽

G.D. Dürr ◽

J.M. Sinning ◽

...

Keyword(s):

Medical Device ◽

Heart Valves ◽

International Medical ◽

Bioprosthetic Heart Valves

Download Full-text

The Effect of Dipyridamole and RA 233 on Human Platelet Function in Vitro

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648112 ◽

1973 ◽

Vol 29 (03) ◽

pp. 694-700 ◽

Cited By ~ 4

Author(s):

Paul L. Rifkin ◽

Marjorie B. Zucker

Keyword(s):

Mechanism Of Action ◽

Human Blood ◽

Glass Bead ◽

Heart Valves ◽

Human Platelet ◽

Drug Effects ◽

Simple Relation ◽

Prosthetic Heart Valves ◽

Induced Aggregation

SummaryDipyridamole (Persantin) is reported to prolong platelet survival and inhibit embolism in patients with prosthetic heart valves, but its mechanism of action is unknown. Fifty jxM dipyridamole failed to reduce the high percentage of platelets retained when heparinized human blood was passed through a glass bead column, but prolonged the inhibition of retention caused by disturbing blood in vitro. Possibly the prostheses act like disturbance. Although RA 233 was as effective as dipyridamole in inhibiting the return of retention, it was less effective in preventing the uptake of adenosine into erythrocytes, and more active in inhibiting ADP-induced aggregation and release. Thus there is no simple relation between these drug effects.

Download Full-text

The role of matrix metalloproteinase 9 and its inhibitors in scarring processes following surgery for primary open-angle glaucoma

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/0031-2991.2019.04.72-80 ◽

2019 ◽

pp. 72-80

Author(s):

Е.В. Маркелова ◽

О.В. Овчинникова ◽

А.С. Хохлова ◽

Л.П. Догадова ◽

А.В. Костюшко ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Postoperative Period ◽

Open Angle Glaucoma ◽

Matrix Metalloproteinase 9 ◽

Tissue Inhibitors Of Metalloproteinases ◽

Open Angle ◽

Tissue Inhibitors ◽

Surgery Outcome ◽

Metalloproteinase 9

Оперативное вмешательство - один из основных методов лечения глаукомы. Однако развитие избыточного рубцевания созданных путей оттока определяет результат хирургического лечения в отдаленные сроки. Процессы рубцевания на данный момент недостаточно изучены. Цель исследования - оценка роли матриксной металлопротеиназы-9, ее ингибиторов в процессах рубцевания у больных с первичной открытоугольной глаукомой после оперативного лечения. Методика. Для выявления возможных маркеров избыточного рубцевания методом твердофазного иммуноферментного анализа определяли содержание матриксных металлопротеиназ-9, тканевых ингибиторов металлопротеиназ 2 и -3 в слезной жидкости у 37 пациентов с активной стадией первичной остроугольной глаукомы в динамике послеоперационного периода. Средний возраст пациентов составил 52,8 лет. В зависимости от исхода оперативного вмешательства все пациенты были разделены на 2 группы - с благоприятным исходом (без избыточного рубцевания) и с неблагоприятным исходом (с избыточным рубцеванием) на месте сформированных дополнительных путей оттока внутриглазной жидкости в послеоперационном периоде. Группа контроля включала 20 человек в возрасте от 50 до 66 лет без сопутствующей офтальмологической и соматической патологии в стадии обострения. Результаты. В динамике показано изменение концентрации матриксной металлопротеиназы-9 и ее ингибиторов в послеоперационном периоде. Анализ данных свидетельствует об обратной зависимости уровня матриксной металлопротеиназы-9 и тканевых ингибиторов металлопротеиназы 2 и 3 типов с исходом операции - чем выше концентрация металлопротеиназы-9 и ниже концентрация тканевых ингибиторов металлопротеиназ 2, -3 в слезной жидкости, тем выше вероятность неблагоприятного исхода в виде рубцевания сформированных дополнительных путей оттока внутриглазной жидкости в послеоперационном периоде. Заключение. Мониторинг уровня металлопротеиназ и их тканевых ингибиторов после проведения хирургического лечения пациентов с первичной открытоугольной глаукомой позволяет прогнозировать раннее рубцевание, дает возможность разработки новых методов лечения как в раннем, так и в позднем послеоперационном периоде. Surgery is one of the major treatments for glaucoma; however excessive scarring of created outflow patways affects the long-term outcome. At the present time, scarring processes are not sufficiently studied. Aim. To evaluate the role of matrix metalloproteinase 9 and its inhibitors in scarring after surgical treatment of open-angle glaucoma. Methods. Concentrations of matrix metalloproteinase 9 and tissue inhibitors of metalloproteinases 2 and 3 were measured in tear fluid of 37 patients (mean age, 52.8) with active primary open-angle glaucoma in dynamics during the postoperative period to identify possible markers of excessive scarring. Based on the surgery outcome, all patients were divided into two groups, with a favorable outcome (without excessive scarring) and an unfavorable outcome (with excessive scarring) in the created additional outflow pathways for the intraocular fluid in the postoperative period. The control group included 20 subjects aged 50-66 without eye disease or somatic disease at exacerbation stage. Results. Analysis of changes in concentrations of matrix metalloproteinase 9 and its inhibitors in the postoperative period showed their inverse relationship with the surgery outcome. The higher was the metalloproteinase 9 level and the lower the level of tissue inhibitors of metalloproteinases 2 and 3 the higher was the probability of unfavorable outcome evident as excessive scarring of the formed additional pathways for tear fluid outflow in the postoperative period. Conclusion. Postoperative monitoring of metalloproteinases and their tissue inhibitors allows to predict early scarring and to develop new treatments both in early and late postoperative periods.

Download Full-text