collagen MMP valve

BACKGROUND AND AIM OF THE STUDY: Mitral leaflet enlargement in patients with chronic aortic regurgitation (AR) has been identified as an adaptive mechanism potentially able to prevent functional mitral regurgitation (FMR) in response to left ventricular (LV) dilatation. The timing of valve enlargement is not known, and the related mechanisms are largely unexplored. METHODS: AR was induced in 58 rats, and another 54 were used as sham controls. Animals were euthanized at different time points after AR creation (48 h, one week, and three months), and AR severity, FMR and LV dilatation were assessed using echocardiography...

OBJECTIVES: To explore expressions of matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinases-1 (TIMP-1) and transforming growth factor-β1 (TGF-β1) in valve tissue of rheumatic heart disease (RHD), and to analyzed their roles in RHD. METHODS: The expressions of MMP-1, TIMP-1 and TGF-β1 proteins and mRNAs were tested by Western blot and RT-PCR methods in valve tissues in participants with (experimental group, n =30) and without RHD (control group, n =15)...

The veins of the lower extremity are equipped with efficient wall, contractile vascular smooth muscle (VSM), and competent valves in order to withstand the high venous hydrostatic pressure in the lower limb and allow unidirectional movement of deoxygenated blood toward the heart. The vein wall structure and function are in part regulated by matrix metalloproteinases (MMPs). MMPs are zinc-dependent endopeptidases that are secreted as inactive pro-MMPs by different cells in the venous wall including fibroblasts, VSM, and leukocytes...

Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of aortic aneurysm because the histology of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) is characterized by the loss of smooth muscle cells in the aortic media and the destruction of extracellular matrix (ECM). Furthermore, AAA have evidence of inflammation and the cellular elements involved in inflammation such as macrophages can produce and/or activate MMPs This chapter focuses on human aortic aneurysm that are not due to specific known genetic causes because this type of aneurysm is the more common type...

Calcific aortic valve disease (CAVD) is a leading cardiovascular disorder in the elderly. Diseased aortic valves are characterized by sclerosis (fibrosis) and nodular calcification. Sclerosis, an early pathological change, is caused by aortic valve interstitial cell (AVIC) proliferation and overproduction of extracellular matrix (ECM) proteins. However, the mechanism of aortic valve sclerosis remains unclear. Recently, we observed that diseased human aortic valves overexpress growth factor neurotrophin 3 (NT3)...

AIMS: The major challenge of working with valvular interstitial cells in vitro is the preservation or recovery of their native quiescent state. In this study, a biomimetic approach is used which aims to engineer small volume, high quality valve microtissues, having a potential in regenerative medicine and as a relevant 3D in vitro model to provide insights into valve (patho)biology. METHODS AND RESULTS: To form micro-aggregates, porcine valvular interstitial cells were seeded in agarose micro-wells and cultured in medium supplemented with 250μM Ascorbic Acid 2-phosphate for 22days...

OBJECTIVE: Rheumatic Heart Disease (RHD), a chronic acquired heart disorder results from Acute Rheumatic Fever. RHD is mostly prevalent in developing nations which is mainly diagnosed by transthoracic echocardiography. Till date, there is no biochemical marker for disease management. In the present study we aim to investigate whether mitral valve remodeling contributes to altered levels of circulating biomarkers of collagen metabolism in rheumatic heart disease. DESIGN AND METHOD: The study involved RHD subjects with before and after valve replacement surgery which includes age and sex matched controls...

OBJECTIVE: Rheumatic Heart Disease (RHD), a chronic acquired heart disorder results from Acute Rheumatic Fever. RHD is mostly prevalent in developing nations which is mainly diagnosed by transthoracic echocardiography. Till date, there is no biochemical marker for disease management. In the present study we aim to investigate whether mitral valve remodeling contributes to altered levels of circulating biomarkers of collagen metabolism in rheumatic heart disease. DESIGN AND METHOD: The study involved RHD subjects with before and after valve replacement surgery which includes age and sex matched controls...

Current options for aortic valve replacements are non-viable and thus lack the ability to grow and remodel, which can be problematic for paediatric applications. Toward the development of living valve substitutes that can grow and remodel, porcine aortic valve interstitial cells (VICs) were isolated and encapsulated within proteolytically degradable and cell-adhesive poly(ethylene glycol) (PEG) hydrogels, in an effort to study their phenotypes and functions. The results showed that encapsulated VICs maintained high viability and proliferated within the hydrogels...

AIMS: We investigated the association between left ventricular (LV) torsional deformation and vascular dysfunction, fibrosis, neurohumoral activation, and exercise capacity in patients with normal ejection fraction METHODS AND RESULTS: In 320 newly-diagnosed untreated hypertensive patients and 160 controls, we measured: pulse wave velocity (PWV); coronary flow reserve (CFR) by Doppler echocardiography; global longitudinal strain and strain rate, peak twisting, the percentage changes between peak twisting, and untwisting at mitral valve opening (%dpTw - UtwMVO ), at peak (%dpTw - UtwPEF ), and the end of early LV diastolic filling (%dpTw - UtwEDF ) by speckle tracking imaging; transforming growth factor (TGFb-1), metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloptoteinase-1(TIMP-1), markers of collagen synthesis, and N-terminal pro-brain natriuretic peptide (NT-proBNP)...

Lower-extremity veins have efficient wall structure and function and competent valves that permit upward movement of deoxygenated blood toward the heart against hydrostatic venous pressure. Matrix metalloproteinases (MMPs) play an important role in maintaining vein wall structure and function. MMPs are zinc-binding endopeptidases secreted as inactive pro-MMPs by fibroblasts, vascular smooth muscle (VSM), and leukocytes. Pro-MMPs are activated by various activators including other MMPs and proteinases. MMPs cause degradation of extracellular matrix (ECM) proteins such as collagen and elastin, and could have additional effects on the endothelium, as well as VSM cell migration, proliferation, Ca(2+) signaling, and contraction...

To determine how extracellular matrix and contractile valvular cells contribute to the heterogeneous motion and strain across the mitral valve (MV) during the cardiac cycle, regional MV material properties, matrix composition, matrix turnover, and cell phenotype were related to regional leaflet strain. Radiopaque markers were implanted into 14 sheep to delineate the septal (SEPT), lateral (LAT), and anterior and posterior commissural leaflets (ANT-C, POST-C). Videofluoroscopy imaging was used to calculate radial and circumferential strains...

PURPOSE: Regional heterogeneity in mitral annular contraction, which is generally ascribed to the fibrous vs. muscular annular composition, ensures proper leaflet motion and timing of coaptation. It is unknown whether the fibroblast-like cells in the annulus modulate this heterogeneity, even though valvular interstitial cells (VICs) can be mechanically "activated." METHODS: Fourteen sheep underwent implantation of radiopaque markers around the mitral annulus defining four segments: septal (SEPT), lateral (LAT), and anterior (ANT-C) and posterior (POST-C) commissures...

Thickening of mitral leaflets, endothelial-to-mesenchymal transition (EndMT), and activated myofibroblast-like interstitial cells have been observed in ischemic mitral valve regurgitation. We set out to determine if interactions between mitral valve endothelial cells (VECs) and interstitial cells (VICs) might affect these alterations. We used in vitro co-culture in Transwell™ inserts to test the hypothesis that VICs secrete factors that inhibit EndMT and conversely, that VECs secrete factors that mitigate the activation of VICs to a myofibroblast-like, activated phenotype...

The hallmarks of calcific aortic valve disease (CAVD) are the significant quantitative and qualitative changes that occur in the extracellular matrix (ECM), which ultimately lead to increased leaflet stiffness and obstruction of left ventricular outflow. Mounting evidence suggests that ECM remodeling not only contribute to valve cell dysfunction but also alter certain cell signaling pathways responsible for the initiation and progression of the disease state. Matrix metalloproteinases (MMPs), collectively called matrixins, are a family of enzymes known to participate in numerous ECM remodeling events during embryonic development and in disease...

Ascending aortic aneurysm (AsAA) is a consequence of medial degeneration (MD), deriving from apoptotic loss of smooth muscle cells (SMC) and fragmentation of elastin and collagen fibers. Alterations of extracellular matrix structure and protein composition, typical of medial degeneration, can modulate intracellular pathways. In this study we examined the relevance of superoxide dismutase (SOD3) and Akt in AsAA pathogenesis, evaluating their tissue distribution and protein levels in ascending aortic tissues from controls (n=6), patients affected by AsAA associated to tricuspid aortic valve (TAV, n=9) or bicuspid aortic valve (BAV, n=9)...

UNLABELLED: An aortic aneurysm is characterized by widening of the aortic lumen diameter with adverse remodelling of the vascular extracellular matrix. A thoracic aortic aneurysm (TAA) is highly prevalent in patients with a bicuspid aortic valve (BAV). We investigated the structural remodelling in the aneurysmal ascending aorta in correlation to molecular alterations in male versus female BAV-TAA patients. Aneurysmal aortic samples (diameter >4.4 cm) from male and female patients were compared to non-aneurysmal non-BAV samples...

BACKGROUND: Increased sympathetic activity, commonly reported in mitral valve prolapse, indicates that the sympathetic nervous system might play an important role in regulating mitral interstitial cells. Hence, the aim of this study is to determine the level and pattern of adrenergic receptors expressed in human mitral valve leaflets and to investigate the effect of norepinephrine on physiologic behaviors of mitral interstitial cells. METHODS AND RESULTS: Immunohistochemistry displayed significantly increased expressions of β1, β2, and α1 adrenergic receptors in mitral valve prolapse...

BACKGROUND: Rheumatic Heart Disease (RHD), a chronic acquired heart disorder results from Acute Rheumatic Fever. It is a major public health concern in developing countries. In RHD, mostly the valves get affected. The present study investigated whether extracellular matrix remodelling in rheumatic valve leads to altered levels of collagen metabolism markers and if such markers can be clinically used to diagnose or monitor disease progression. METHODOLOGY: This is a case control study comprising 118 subjects...

Pannus formation is an infrequent but serious complication of prosthetic heart valve surgery. The cause of pannus is recognized as a bioreaction to the prostheses; histological investigations have shown that pannus comprises collagen and elastic tissues containing endothelial cells, chronic inflammatory cells, and myofibroblasts. However, the detailed mechanism of its formation has not been fully demonstrated. We aimed to evaluate the potential role of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in the pathogenesis of pannus formation in three patients with mechanical prosthetic heart valves...