Cellular and Extracellular Matrix Basis for Heterogeneity in Mitral Annular Contraction

Fahrenholtz, Monica; Connell, Patrick S.; Timek, Tomasz A.; Daughters, George T.; Kuo, Joyce J.; Patton, Aaron M.; Ingels, Neil B.; Miller, D. Craig; Grande-Allen, K. Jane

doi:10.1007/s13239-014-0209-3

Cited by 3 publications

(2 citation statements)

References 30 publications

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“…Homeostasis of the ECM in adult valves is largely mediated by a population of valve interstitial cells (VICs) that reside within the core of the leaflets . Once considered a homogeneous population of fibroblast‐like cells, VICs are now being described as heterogeneous based on their differential molecular profiles and diverse embryonic origins . A single layer of valve endothelial cells (VECs) covers the leaflet surface and encapsulates the VICs and ECM.…”

Section: Introductionmentioning

confidence: 99%

“…2 Once considered a homogeneous population of fibroblast-like cells, VICs are now being described as heterogeneous based on their differential molecular profiles and diverse embryonic origins. [3][4][5] A single layer of valve endothelial cells (VECs) covers the leaflet surface and encapsulates the VICs and ECM. Their function is to serve as a physical barrier against the hemodynamic environment and molecularly communicate with underlying VICs to regulate their behavior.…”

mentioning

confidence: 99%

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Contribution of Extra‐Cardiac Cells in Murine Heart Valves is Age‐Dependent

Anstine

Horne

Horwitz

et al. 2017

JAHA

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BackgroundHeart valves are dynamic structures that open and close over 100 000 times a day to maintain unidirectional blood flow during the cardiac cycle. Function is largely achieved by highly organized layers of extracellular matrix that provide the necessary biomechanical properties. Homeostasis of valve extracellular matrix is mediated by valve endothelial and interstitial cell populations, and although the embryonic origins of these cells are known, it is not clear how they are maintained after birth. The goal of this study is to examine the contribution of extracardiac cells to the aortic valve structure with aging using lineage tracing and bone marrow transplantation approaches.Methods and ResultsImmunohistochemistry and fate mapping studies using CD45‐Cre mice show that the contribution of hematopoietic‐derived cells to heart valve structures begins during embryogenesis and increases with age. Short‐term (6 weeks), CD45‐derived cells maintain CD45 expression and the majority coexpress monocyte markers (CD11b), whereas coexpression with valve endothelial (CD31) and interstitial (Vimentin) cell markers were infrequent. Similar molecular phenotypes are observed in heart valves of irradiated donor mice following transplantation of whole bone marrow cells, and engraftment efficiency in this tissue is age‐dependent.ConclusionsFindings from this study demonstrate that the percentage of CD45‐positive extracardiac cells reside within endothelial and interstitial regions of heart valve structures increases with age. In addition, bone transplantation studies show that engraftment is dependent on the age of the donor and age of the tissue environment of the recipient. These studies create a foundation for further work defining the role of extracardiac cells in homeostatic and diseased heart valves.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Contribution of Extra‐Cardiac Cells in Murine Heart Valves is Age‐Dependent

Anstine

Horne

Horwitz

et al. 2017

JAHA

View full text Add to dashboard Cite

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Mechanical Properties and Composition of the Basal Leaflet-Annulus Region of the Tricuspid Valve

Basu

Lacerda

2018

Cardiovasc Eng Tech

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The Tricuspid valve (TV) annulus is a transition structure from the leaflets to the myocardium, with 3 different annulus segments corresponding to the TV leaflets, which includes both basal leaflets and bordering myocardium. The objective of this study was to understand TV annulus mechanical properties and correlate it to the biological composition. The uniaxial testing of the annulus segments from ten porcine TVs was performed to measure Young's modulus (E) and extensibility (ε). Western blotting and histology were executed. The septal annulus E value (208.7 ± 67.2 kPa) was statistically greater (p < 0.01) than that of the anterior (92.0 ± 66.8 kPa) and the posterior annulus segment (136.8 ± 56.9 kPa) (p < 0.05), respectively. ε among the 3 segments were equivalent (p values < 0.05). Western blotting and histology indicated that collagen was greatest along the septal annulus segment, which is correlated to E values. Collagen fibers from the leaflets inserted into the myocardium and faded out. Collagen content explains greater E and suture strength in the surgical annulus repair and larger resistance to annulus dilation in the septal annulus as compared with other segments. This study elucidates new knowledge of mechanical properties of the basal leaflet-annulus region of the TV annulus, which can be useful for future TV repair techniques.

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The Effect of Acute Pulmonary Hypertension on Tricuspid Annular Height, Strain, and Curvature in Sheep

Rausch

Malinowski

Meador

et al. 2018

Cardiovasc Eng Tech

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The tricuspid annulus shows significant alterations in patients with functional tricuspid regurgitation-tricuspid valve dysfunction that is secondary to other diseases such as pulmonary hypertension. Early changes in annular shape and dynamics may provide an understanding of disease mechanisms and could predict disease progression. To gain a mechanistic insight into these early changes we perform a spatially-resolved analysis of the effect of acute pulmonary hypertension on the tricuspid annulus in sheep. To this end, we suture sonomicrometry crystals to the annulus of nine sheep and record their locations in the beating heart, before and after inducing acute pulmonary hypertension. Using least-squares cubic splines, we derive mathematical representations of the annulus to describe pulmonary hypertension-induced annular shape changes via strain, relative curvature, and relative annular height between the control group and the acute pulmonary hypertension group. Moreover, we determine hypertension-induced alterations to annular dynamics as within-group strains, relative curvature, and relative height throughout the cardiac cycle for each group. We confirm that the annulus in acute pulmonary hypertension dilates significantly, becomes more circular, and flattens. Our regional analysis reveals that annular dilation, circularization, and flattening are driven by highly localized changes in annular strains, curvature, and height. Additionally, we find that acute pulmonary hypertension alters annular dynamics, albeit minimally. This regionally-resolved analysis of acute hypertension-induced changes of annular shape and dynamics provides insight into early disease mechanisms, and may inspire future generations of annuloplasty devices and techniques that address spatial annular heterogeneities.

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Cellular and Extracellular Matrix Basis for Heterogeneity in Mitral Annular Contraction

Cited by 3 publications

References 30 publications

Contribution of Extra‐Cardiac Cells in Murine Heart Valves is Age‐Dependent

Contribution of Extra‐Cardiac Cells in Murine Heart Valves is Age‐Dependent

Mechanical Properties and Composition of the Basal Leaflet-Annulus Region of the Tricuspid Valve

The Effect of Acute Pulmonary Hypertension on Tricuspid Annular Height, Strain, and Curvature in Sheep

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