fibrin and Heart-Valve-Diseases

Aortic valve disease is the most common valvular heart disease leading to valve replacement. The efficacy of pharmacological therapy for aortic valve disease is limited by the high mechanical stress at the aortic valves impairing the binding rate. We aimed to identify nanoparticle coating with entire platelet membranes to fully mimic their inherent multiple adhesive mechanisms and target the sclerotic aortic valve of apolipoprotein E-deficient (ApoE. Considering the potent interaction of platelet membrane glycoproteins with components present in sclerotic aortic valves, platelet membrane-coated nanoparticles (PNPs) were synthetized and the binding capacity under high shear stress was evaluated in vitro and in vivo.. PNPs demonstrated effectively adhering to von Willebrand factor, collagen and fibrin under shear stresses in vitro. In an aortic valve disease model established in ApoE. PNPs could provide a promising platform for the molecular diagnosis and targeting treatment of aortic valve disease.

Topics: Animals; Aortic Valve; Apolipoproteins E; Bicuspid Aortic Valve Disease; Blood Platelets; Cell Membrane; Collagen; Disease Models, Animal; Fibrin; Heart Defects, Congenital; Heart Valve Diseases; Human Umbilical Vein Endothelial Cells; Humans; Male; Mice, Inbred C57BL; Mice, Knockout, ApoE; Nanoparticles; Polylactic Acid-Polyglycolic Acid Copolymer; Sclerosis; Stress, Mechanical; von Willebrand Factor

Topics: Aged, 80 and over; Aortic Valve; Blood Platelets; Echocardiography, Transesophageal; Fibrin; Fibrosis; Heart Neoplasms; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Male; Myxoma; Neutrophils; Thrombectomy; Thrombosis

Diseased aortic valves often require replacement, with over 30% of the current aortic valve surgeries performed in patients who will outlive a bioprosthetic valve. While many promising tissue-engineered valves have been created in the lab using the cell-seeded polymeric scaffold paradigm, none have been successfully tested long-term in the aortic position of a pre-clinical model. The high pressure gradients and dynamic flow across the aortic valve leaflets require engineering a tissue that has the strength and compliance to withstand high mechanical demand without compromising normal hemodynamics. A long-term preclinical evaluation of an off-the-shelf tissue-engineered aortic valve in the sheep model is presented here. The valves were made from a tube of decellularized cell-produced matrix mounted on a frame. The engineered matrix is primarily composed of collagen, with strength and organization comparable to native valve leaflets. In vitro testing showed excellent hemodynamic performance with low regurgitation, low systolic pressure gradient, and large orifice area. The implanted valves showed large-scale leaflet motion and maintained effective orifice area throughout the duration of the 6-month implant, with no calcification. After 24 weeks implantation (over 17 million cycles), the valves showed no change in tensile mechanical properties. In addition, histology and DNA quantitation showed repopulation of the engineered matrix with interstitial-like cells and endothelialization. New extracellular matrix deposition, including elastin, further demonstrates positive tissue remodeling in addition to recellularization and valve function. Long-term implantation in the sheep model resulted in functionality, matrix remodeling, and recellularization, unprecedented results for a tissue-engineered aortic valve.

Topics: Animals; Aortic Valve; Biocompatible Materials; Bioprosthesis; Collagen; Extracellular Matrix; Fibrin; Fibroblasts; Heart Valve Diseases; Heart Valve Prosthesis; Hemodynamics; Humans; Polymers; Prosthesis Design; Sheep; Skin; Stress, Mechanical; Tensile Strength; Time Factors; Tissue Engineering

Mesothelial/monocytic incidental cardiac excrescence (MICE) is a rare benign lesion composed of a mixture of histiocytes, mesothelial cells, fibrin, adipocytes and scattered inflammatory cells without a vascular network or supporting stroma. Its pathogenesis is controversial with some authors favoring an artifactual theory while others consider a reactive phenomenon. To date, only 41 cases of MICE have been reported in the literature. We describe an additional case of MICE in a 24-year-old female with antiphospholipid syndrome. A mobile hyperechogenic mass attached to the left ventricular surface of the aortic valve was documented by transthoracic echocardiography (TTE). The patient did have cardiac catheterization one month before the cardiac surgery. Histopathologic and immunohistochemical examination showed a lesion composed of histiocytes and mesothelial cells together with fibrin and scattered inflammatory cells. To our knowledge, this is the first case of MICE detected in a patient with antiphospholipid syndrome.

Topics: Antiphospholipid Syndrome; Aortic Valve; Biomarkers; Cardiac Surgical Procedures; Epithelium; Female; Fibrin; Heart Valve Diseases; Histiocytes; Humans; Immunohistochemistry; Treatment Outcome; Ultrasonography; Young Adult

The lack of therapies that inhibit valvular calcification and the conflicting outcomes of clinical studies regarding the impact of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors on valve disease highlight the need for controlled investigations to characterize the interactions between HMG-CoA reductase inhibitors and valve tissue. Thus, we applied multiple in vitro disease stimuli to valvular interstitial cell (VIC) cultures and examined the impact of simvastatin treatment on VIC function.. VICs were cultured on 3 different substrates that supported various levels of nodule formation. Transforming growth factor (TGF)-beta1 was also applied as a disease stimulus to VICs on 2-D surfaces or encapsulated in 3-D collagen gels and combined with different temporal applications of simvastatin. Simvastatin inhibited calcific nodule formation in a dose-dependent manner on all materials, although the level of statin efficacy was highly substrate-dependent. Simvastatin treatment significantly altered nodule morphology, resulting in dramatic nodule dissipation over time, also in a substrate-dependent manner. These effects were mimicked in 3-D cultures, wherein simvastatin reversed TGF-beta1-induced contraction. Decreases in nodule formation were not achieved via the HMG-CoA reductase pathway, but were correlated with decreases in ROCK activity.. These studies represent a significant contribution to understanding how simvastatin may impact heart valve calcification.

Topics: Animals; Aortic Valve; Calcinosis; Cell Culture Techniques; Cells, Cultured; Collagen; Dose-Response Relationship, Drug; Extracellular Matrix; Fibrin; Gels; Heart Valve Diseases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Laminin; Mevalonic Acid; Polystyrenes; rho-Associated Kinases; Simvastatin; Swine; Time Factors; Transforming Growth Factor beta1

Filamentous fibrin strands (FSs) attached to valve prostheses have been well described in patients undergoing transesophageal echocardiography, but the frequency and clinical significance of these strands remain poorly defined. The aims of this study were to determine the frequency of prosthetic valve strands and to assess their significance in relation to clinical cerebral ischemic events (CIEs) and anticoagulant status.. Three hundred consecutive patients with 421 prosthetic heart valves were evaluated for the presence of FSs (highly mobile, filamentous masses<1 mm thick).. FSs were found in 139 patients (49%) and 147 prostheses (38%) in patients with left-sided prostheses, with a significant association between FSs, CIEs, and anticoagulant status (P<.001). A lower international normalized ratio (<2.5) had a positive association with the occurrence of CIEs.. There is a significant association between FSs, CIEs, and patient's anticoagulant status; therefore, aggressive anticoagulation and close follow-up are recommended for these patients.

Topics: Adolescent; Adult; Comorbidity; Female; Fibrin; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Incidence; Iran; Male; Middle Aged; Postoperative Complications; Risk Assessment; Risk Factors; Thrombosis; Ultrasonography; Young Adult

Topics: Adolescent; Adult; Comorbidity; Female; Fibrin; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Incidence; Iran; Male; Middle Aged; Postoperative Complications; Risk Assessment; Risk Factors; Thrombosis; Ultrasonography; Young Adult

The incidence of stroke in patients suffering atrial fibrillation (AF) is increased when left atrial enlargement occurs. Recently, the platelet adhesive molecule, von Willebrand factor (vWF), located in the atrial endocardium, has been shown to be increased in patients with a variety of heart diseases compared with patients who have no cardiac problems.. We investigated the expression of vWF mRNA and protein in the endocardium as a possible prothrombotic alteration of AF in association with atrial structural remodeling. Atrial appendage specimens were obtained during either heart surgery or at an autopsy from AF patients with and without underlying heart disease. The immunohistochemical and in situ hybridization signals for vWF in the endocardium were well correlated and varied widely among the individual atrial appendages examined. The increased expression of vWF in the endocardium was associated with enlarged left atrial dimensions in mitral valvular disease or increased myocyte diameters in the underlying myocardium. Platelet adhesion/aggregation on the endocardium was always found under the fresh thrombi and was colocalized with strong vWF staining, but not necessarily with fibrinogen and/or fibrin staining.. Endocardial overexpression of vWF may occur during the process of atrial structural remodeling contributing to the thrombotic predilection of AF in association with underlying heart disease.

Topics: Adult; Aged; Aged, 80 and over; Atrial Appendage; Atrial Fibrillation; Atrial Function; Endocardium; Female; Fibrin; Fibrinogen; Gene Expression; Heart Atria; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve; Platelet Endothelial Cell Adhesion Molecule-1; RNA, Messenger; Thrombophilia; von Willebrand Factor

Invasive resuscitative and supportive therapy subsequent to accidental trauma, assault, or medical mishap may create lesions that forensic pathologists must interpret. Pulmonary valve nonbacterial endocarditis sometimes complicates placement of flow-directed pulmonary artery (Swan-Ganz) catheters. We examined ten cases of endocarditis from patients dying 0-10 days after removal of a Swan-Ganz catheter, and compared the natural evolution of vegetations in critically ill patients with the reported evolution of similar vegetations in experimental animals in the Freedman model. There was wide variation in macroscopic, as well as in the light- and scanning electron-microscopic, appearances in our cases and we could not establish a direct relationship between vegetation structure and time elapsed after removal of the catheter. These findings suggest that parameters related to critical illness and species account for the differences between this disease in human and animal models.

Topics: Catheterization, Swan-Ganz; Endocarditis; Endothelium; Fibrin; Heart Valve Diseases; Humans; Microscopy, Electron, Scanning; Pulmonary Valve; Tricuspid Valve

Topics: Adult; Aged; Aortic Valve; Bioprosthesis; Endocarditis, Bacterial; Female; Fibrin; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Microscopy, Electron, Scanning; Middle Aged; Mitral Valve; Postoperative Complications; Prosthesis Design; Prosthesis Failure; Thrombosis

Gross anatomic, histologic, and transmission and scanning electron microscopic observations were made of 29 bioprosthetic valves that had been implanted in patients for up to 115 months. On the basis of these morphologic data, no significant evidence of tissue rejection was seen. However, the durability of these valve bioprostheses is still questionable. Our observation primarily emphasize three factors: (1) disruption of the endothelial cell barrier and the lack of significant host endothelialization even 115 months after transplantation; (2) increased permeability that eased diffusion of circulating host plasma proteins into valve tissue, and increased activity of infiltration processes, eg. calcification and lipid accumulation; and (3) biodegradation of the collagen framework. Each of these factors may contribute further to valve dysfunction. Development of an intimal fibrous sheath seems to occur in porcine bioprostheses that have been implanted for the longest periods of time, but the rate of host tissue ingrowth varies.

Topics: Adolescent; Adult; Aged; Aldehydes; Aortic Valve; Bioprosthesis; Calcinosis; Child; Collagen; Connective Tissue; Endocarditis; Endothelium; Evaluation Studies as Topic; Female; Fibrin; Glutaral; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Mediastinitis; Methods; Microscopy, Electron, Scanning; Middle Aged; Mitral Valve

The association of fibrin and tumour cells on a sclerosed mitral valve in a 62-year-old woman is described. This was the first indication of malignant disease but bilateral ovarian cancer was proved two months later. ino further tumour deposits have been found in fifteen months. The tumour deposit on the valve was most likely a metastasis but primary heart valve sarcoma has not been positively excluded. If the lesion was a secondary deposit this has possible implications for the role of fibrin in metastasis in humans.

Topics: Female; Fibrin; Heart Neoplasms; Heart Valve Diseases; Humans; Middle Aged; Mitral Valve; Neoplasm Metastasis; Neoplastic Cells, Circulating; Ovarian Neoplasms; Ovary; Sarcoma; Sclerosis

Topics: Adult; Aortic Valve; Capillaries; Epithelial Cells; Erythrocytes; Ethylene Oxide; Fibrin; Fibroblasts; Heart Valve Diseases; Heart Valves; Humans; Lactones; Leukocytes; Lymphocytes; Macrophages; Microscopy, Electron; Middle Aged; Plasma Cells; Rupture, Spontaneous; Sterilization; Transplantation, Homologous

Topics: Adult; Aged; Autopsy; Collagen; Erythrocytes; Fascia; Fascia Lata; Female; Fibrin; Fibroblasts; Foreign Bodies; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Leukocytes; Macrophages; Male; Middle Aged; Mitral Valve; Transplantation, Autologous; Tricuspid Valve

Topics: Acute Disease; Animals; Antigens; Antigens, Viral; Chronic Disease; Coxsackievirus Infections; Endocarditis; Endocardium; Enterovirus; Fibrin; Fluorescent Antibody Technique; Heart Valve Diseases; Injections, Intraperitoneal; Mice; Myocardium; Rheumatic Heart Disease