scholarly journals Molecular and functional characteristics of heart-valve interstitial cells

2007 ◽  
Vol 362 (1484) ◽  
pp. 1437-1443 ◽  
Author(s):  
Adrian H Chester ◽  
Patricia M Taylor

The cells that reside within valve cusps play an integral role in the durability and function of heart valves. There are principally two types of cells found in cusp tissue: the endothelial cells that cover the surface of the cusps and the interstitial cells (ICs) that form a network within the extracellular matrix (ECM) within the body of the cusp. Both cell types exhibit unique functions that are unlike those of other endothelial and ICs found throughout the body. The valve ICs express a complex pattern of cell-surface, cytoskeletal and muscle proteins. They are able to bind to, and communicate with, each other and the ECM. The endothelial cells on the outflow and inflow surfaces of the valve differ from one another. Their individual characteristics and functions reflect the fact that they are exposed to separate patterns of flow and pressure. In addition to providing a structural role in the valve, it is now known that the biological function of valve cells is important in maintaining the integrity of the cusps and the optimum function of the valve. In response to inappropriate stimuli, valve interstitial and endothelial cells may also participate in processes that lead to valve degeneration and calcification. Understanding the complex biology of valve interstitial and endothelial cells is an important requirement in elucidating the mechanisms that regulate valve function in health and disease, as well as setting a benchmark for the function of cells that may be used to tissue engineer a heart valve.

2020 ◽  
Vol 2 (1) ◽  
pp. R59-R71
Author(s):  
Chia-Pei Denise Hsu ◽  
Joshua D Hutcheson ◽  
Sharan Ramaswamy

Forces generated by blood flow are known to contribute to cardiovascular development and remodeling. These hemodynamic forces induce molecular signals that are communicated from the endothelium to various cell types. The cardiovascular system consists of the heart and the vasculature, and together they deliver nutrients throughout the body. While heart valves and blood vessels experience different environmental forces and differ in morphology as well as cell types, they both can undergo pathological remodeling and become susceptible to calcification. In addition, while the plaque morphology is similar in valvular and vascular diseases, therapeutic targets available for the latter condition are not effective in the management of heart valve calcification. Therefore, research in valvular and vascular pathologies and treatments have largely remained independent. Nonetheless, understanding the similarities and differences in development, calcific/fibrous pathologies and healthy remodeling events between the valvular and vascular systems can help us better identify future treatments for both types of tissues, particularly for heart valve pathologies which have been understudied in comparison to arterial diseases.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuan-chi Teng ◽  
Alfredo Leonardo Porfírio-Sousa ◽  
Giulia Magri Ribeiro ◽  
Marcela Corso Arend ◽  
Lindolfo da Silva Meirelles ◽  
...  

Abstract Background Peripheral arterial disease (PAD) affects millions of people and compromises quality of life. Critical limb ischemia (CLI), which is the most advanced stage of PAD, can cause nonhealing ulcers and strong chronic pain, and it shortens the patients’ life expectancy. Cell-based angiogenic therapies are becoming a real therapeutic approach to treat CLI. Pericytes are cells that surround vascular endothelial cells to reinforce vessel integrity and regulate local blood pressure and metabolism. In the past decade, researchers also found that pericytes may function as stem or progenitor cells in the body, showing the potential to differentiate into several cell types. We investigated the gene expression profiles of pericytes during the early stages of limb ischemia, as well as the alterations in pericyte subpopulations to better understand the behavior of pericytes under ischemic conditions. Methods In this study, we used a hindlimb ischemia model to mimic CLI in C57/BL6 mice and explore the role of pericytes in regeneration. To this end, muscle pericytes were isolated at different time points after the induction of ischemia. The phenotypes and transcriptomic profiles of the pericytes isolated at these discrete time points were assessed using flow cytometry and RNA sequencing. Results Ischemia triggered proliferation and migration and upregulated the expression of myogenesis-related transcripts in pericytes. Furthermore, the transcriptomic analysis also revealed that pericytes induce or upregulate the expression of a number of cytokines with effects on endothelial cells, leukocyte chemoattraction, or the activation of inflammatory cells. Conclusions Our findings provide a database that will improve our understanding of skeletal muscle pericyte biology under ischemic conditions, which may be useful for the development of novel pericyte-based cell and gene therapies.


Author(s):  
Emmi Helle ◽  
Minna Ampuja ◽  
Alexandra Dainis ◽  
Laura Antola ◽  
Elina Temmes ◽  
...  

Cell-cell interactions are crucial for organ development and function. In the heart, endothelial cells engage in bidirectional communication with cardiomyocytes regulating cardiac development and growth. We aimed to elucidate the organotypic development of cardiac endothelial cells and cardiomyocyte and endothelial cell crosstalk using human induced pluripotent stem cells (hiPSC). Single-cell RNA sequencing was performed with hiPSC-derived cardiomyocytes (hiPS-CMs) and endothelial cells (hiPS-ECs) in mono- and co-culture. The presence of hiPS-CMs led to increased expression of transcripts related to vascular development and maturation, cardiac development, as well as cardiac endothelial cell and endocardium-specific genes in hiPS-ECs. Interestingly, co-culture induced the expression of cardiomyocyte myofibrillar genes and MYL7 and MYL4 protein expression was detected in hiPS-ECs. Major regulators of BMP- and Notch-signaling pathways were induced in both cell types in co-culture. These results reflect the findings from animal studies and extend them to human endothelial cells, demonstrating the importance of EC-CM interactions during development.


Author(s):  
Soontaree Petchdee ◽  
Wilairat Chumsing ◽  
Suruk Udomsom ◽  
Kittiya Thunsiri

Myxomatous mitral valve degeneration is the most acquired heart disease in dogs. To reduce the clinical progression of mitral valve degeneration and achieve the hemodynamic outcomes, many medical or surgical treatments have been motivated. The objectives of this study is to investigate the suitability of puppy deciduous teeth stem cells as a cell source for tissue engineered heart valves in dog with degenerative valve disease. Puppy deciduous teeth stem cells (pDSCs) were seeded on the scaffolds which made from polylactic acid (PLA), polycaprolactone (PLC) and silicone. The mechanical properties of the tissue engineered heart valves leaflets were characterized by biaxial tensile tests. Results showed that, deciduous teeth stem cells capable of differentiating into a variety of cell types. However, the ability of puppy deciduous teeth stem cells to differentiate declined with increasing passage number which correspond to the number of protein surface marker detection have been shown to decrease substantially by the fifth passage. PLA scaffold is significantly higher tensile strength than other materials. However, silicone showed the highest flaccidity. The results from this study may provide high regenerative capability and the essential information for future directions of heart valve tissue engineering.


2019 ◽  
Vol 20 (18) ◽  
pp. 4411 ◽  
Author(s):  
Krüger-Genge ◽  
Blocki ◽  
Franke ◽  
Jung

The vascular endothelium, a monolayer of endothelial cells (EC), constitutes the inner cellular lining of arteries, veins and capillaries and therefore is in direct contact with the components and cells of blood. The endothelium is not only a mere barrier between blood and tissues but also an endocrine organ. It actively controls the degree of vascular relaxation and constriction, and the extravasation of solutes, fluid, macromolecules and hormones, as well as that of platelets and blood cells. Through control of vascular tone, EC regulate the regional blood flow. They also direct inflammatory cells to foreign materials, areas in need of repair or defense against infections. In addition, EC are important in controlling blood fluidity, platelet adhesion and aggregation, leukocyte activation, adhesion, and transmigration. They also tightly keep the balance between coagulation and fibrinolysis and play a major role in the regulation of immune responses, inflammation and angiogenesis. To fulfill these different tasks, EC are heterogeneous and perform distinctly in the various organs and along the vascular tree. Important morphological, physiological and phenotypic differences between EC in the different parts of the arterial tree as well as between arteries and veins optimally support their specified functions in these vascular areas. This review updates the current knowledge about the morphology and function of endothelial cells, particularly their differences in different localizations around the body paying attention specifically to their different responses to physical, biochemical and environmental stimuli considering the different origins of the EC.


2017 ◽  
Vol 145 ◽  
pp. S150
Author(s):  
Kin Ming Kwan ◽  
Pak Lun Baggio Liu ◽  
Ka Kui Tong

Basement membranes are distributed widely in the body forming an extracellular matrix for epithelial and endothelial cells. The collagenous and glycoprotein constituents of basement membranes are synthesized by these two cell types. Disturbance of the interactions between basement membranes and their associated epithelial and endothelial cells can lead to the pathological changes seen in diseases involving basement membranes. These changes are illustrated here by reference to glomerulonephritis induced by the deposition of immune complexes in the glomerulus of the kidney, and chronic inflammatory changes occurring in the lung after inhalation of asbestos. In these diseases basement membrane changes can occur in several ways. Hydrolytic enzymes released from inflammatory cells degrade basement membranes while other factors released from these cells may stimulate synthesis of basement membrane constituents by epithelial and endothelial cells. Alternatively the physical separation of epithelial and endothelial cells from their basement membranes by space-occupying substances such as immune complexes can interfere with feedback mechanisms leading to synthesis of basement membrane constituents and cell proliferation. Studies of these pathological changes at a cellular level should shed new light on the ways in which cells interact with their pericellular environment.


Author(s):  
Andreas Hagendorff ◽  
Elie Chammas ◽  
Mohammed Rafique Essop

The high spatial and temporal resolution, widespread availability, and non-invasive nature of echocardiography make it the imaging modality of choice for assessment of cardiac valvular disease. Echocardiography allows not only detailed evaluation of valve morphology, but also makes possible assessment of the haemodynamic consequences and impact on left and right ventricular size and function. Based on this data, a more informed decision may be made on the nature and timing of surgical or percutaneous intervention. A wide variety of diseases may afflict the cardiac valves. In some such as rheumatic heart disease and degenerative disease, abnormality of valve function is the most important manifestation. Many systemic diseases, however, may affect the cardiac valves and not infrequently, echocardiography may be the first clue to a systemic illness. The salient points of diseases affecting mainly the cardiac valves are discussed in this chapter.


1995 ◽  
Vol 311 (2) ◽  
pp. 589-594 ◽  
Author(s):  
J S Wiley ◽  
J R Chen ◽  
G P Jamieson ◽  
P J Thurlow

Recirculation of lymphocytes through the body involves their frequent adhesion to endothelial cells but little is known of the signalling pathways between these two cell types. Lymphocytes from patients with chronic lymphocytic leukaemia were loaded with the Ca(2+)-sensitive indicator, fura 2, and allowed to adhere to either glass or monolayers of human umbilical-vein endothelial cells. Addition of ATP or UTP (1-10 microM) to the superfusate produced a transient rise in cytosolic Ca2+ concentration in the lymphocytes adherent to endothelium (24 of 35 cells). In contrast, ATP or UTP (1-10 microM) had no effect on the cytosolic Ca2+ of lymphocytes attached to glass. As the only lymphocyte receptor for ATP (P2Z class) requires higher ATP concentrations (> 50 microM) for Ca2+ influx and is unresponsive to UTP, the involvement of a lymphocyte P2Z purinoceptor is unlikely. Various agonists including ATP, UTP, 2-methylthioATP, ADP and histamine all stimulated increases in endothelial cytosolic Ca2+ but only ATP and UTP (both agonists for endothelial P2U purinoceptors) triggered Ca2+ transients in adherent lymphocytes. Removal of extracellular Ca2+ did not abolish the ATP-induced rise in cytosolic Ca2+ concentration in lymphocytes adherent to endothelial cells. These findings show that stimulation of endothelial P2U purinoceptors triggers an endothelial-lymphocyte signalling pathway which releases internal Ca2+ in adherent lymphocytes.


2005 ◽  
Vol 53 (5) ◽  
pp. 671-677 ◽  
Author(s):  
Chandikumar S. Elangbam ◽  
Ruth M. Lightfoot ◽  
Lawrence W. Yoon ◽  
Donald R. Creech ◽  
Robert S. Geske ◽  
...  

5-Hydroxytryptamine-2B receptor (5HT2BR) stimulation is known to cause fibroblast mitogenesis, and the mitogenic effect has been proposed to trigger valvular heart disease in humans. In this study, we used real-time polymerase chain reaction (TaqMan) to quantify transcript levels of 5HT2B, 5HT2C, and 5HT1B receptors and immunohistochemistry (IHC) to detect the tissue localization of these receptors in the normal heart valves of cynomolgus (CM) monkeys and Sprague-Dawley (S-D) rats. In both species, positive immunostaining was noted for 5HT1B and 5HT2B receptors in mitral, tricuspid, aortic, and pulmonary valves, and the cell types showing positive staining were interstitial cells and endothelial cells lining the valve leaflet. In CM monkeys, 5HT2CR was expressed only in the endothelial cells lining the leaflet, whereas S-D valves were negative for this receptor. IHC results were correlated with 5HT2B and 5HT1B receptor transcripts for all four valves. However, 5HT2C receptor transcripts were lower than 5HT2B or 5HT1B in all CM monkey valves, whereas 5HT2C transcripts were below the level of detection in any of the S-D rat valves. Our data showed the expression of 5HT2B, 5HT1B, and 5HT2C receptors in the normal heart valves of CM monkeys and S-D rats, and IHC and TaqMan techniques may be used to study the potential mechanism of compounds with 5HT2BR agonist activity.


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