Fluid Dynamics of Heart Development

Santhanakrishnan, Arvind; Miller, Laura A.

doi:10.1007/s12013-011-9158-8

Cited by 62 publications

(72 citation statements)

References 105 publications

(122 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Extensive study of intracardiac fluid forces during cardiovascular development has demonstrated important roles in valvulogenesis and trabeculation [1,2,37,38]. Our results suggest that cardiogenesis is also regulated by extracardiac flow forces generated in the pericardial cavity.…”

Section: Discussionmentioning

confidence: 56%

Heartbeat-Driven Pericardiac Fluid Forces Contribute to Epicardium Morphogenesis

et al. 2013

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 56%

Heartbeat-Driven Pericardiac Fluid Forces Contribute to Epicardium Morphogenesis

et al. 2013

View full text Add to dashboard Cite

show abstract

“…In the heart, the highest level of X-gal staining at E11.5 was observed in the endothelium lining ventricular outflow tract and atrioventricular canal (Fig. 2C), areas predicted to experience strong fluid shear forces generated by blood flow (30,31).…”

Section: Piezo1mentioning

confidence: 99%

Piezo1, a mechanically activated ion channel, is required for vascular development in mice

Ranade

Qiu

Woo

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

726

716

View full text Add to dashboard Cite

Mechanosensation is perhaps the last sensory modality not understood at the molecular level. Ion channels that sense mechanical force are postulated to play critical roles in a variety of biological processes including sensing touch/pain (somatosensation), sound (hearing), and shear stress (cardiovascular physiology); however, the identity of these ion channels has remained elusive. We previously identified Piezo1 and Piezo2 as mechanically activated cation channels that are expressed in many mechanosensitive cell types. Here, we show that Piezo1 is expressed in endothelial cells of developing blood vessels in mice. Piezo1-deficient embryos die at midgestation with defects in vascular remodeling, a process critically influenced by blood flow. We demonstrate that Piezo1 is activated by shear stress, the major type of mechanical force experienced by endothelial cells in response to blood flow. Furthermore, loss of Piezo1 in endothelial cells leads to deficits in stress fiber and cellular orientation in response to shear stress, linking Piezo1 mechanotransduction to regulation of cell morphology. These findings highlight an essential role of mammalian Piezo1 in vascular development during embryonic development.

show abstract

“…However, the influence of mechanical forces and its synergy with tissue architecture in influencing cardiac valve EMT is unknown. During embryonic development, valve morphogenesis has been correlated with an increase in fluid shear stresses, mechanical strains, and altered geometry of the developing heart (19)(20)(21)(22). These observations potentially suggests interaction between mechanical forces and the factors that regulate EMT.…”

mentioning

confidence: 99%

Cyclic strain induces dual-mode endothelial-mesenchymal transformation of the cardiac valve

Balachandran

Alford

Wylie-Sears

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

154

123

View full text Add to dashboard Cite

Endothelial-mesenchymal transformation (EMT) is a critical event for the embryonic morphogenesis of cardiac valves. Inducers of EMT during valvulogenesis include VEGF, TGF-β1, and wnt/β-catenin (where wnt refers to the wingless-type mammary tumor virus integration site family of proteins), that are regulated in a spatiotemporal manner. EMT has also been observed in diseased, strain-overloaded valve leaflets, suggesting a regulatory role for mechanical strain. Although the preponderance of studies have focused on the role of soluble mitogens, we asked if the valve tissue microenvironment contributed to EMT. To recapitulate these microenvironments in a controlled, in vitro environment, we engineered 2D valve endothelium from sheep valve endothelial cells, using microcontact printing to mimic the regions of isotropy and anisotropy of the leaflet, and applied cyclic mechanical strain in an attempt to induce EMT. We measured EMT in response to both low (10%) and high strain (20%), where low-strain EMT occurred via increased TGF-β1 signaling and high strain via increased wnt/β-catenin signaling, suggesting dual strain-dependent routes to distinguish EMT in healthy versus diseased valve tissue. The effect was also directionally dependent, where cyclic strain applied orthogonal to axis of the engineered valve endothelium alignment resulted in severe disruption of cell microarchitecture and greater EMT. Once transformed, these tissues exhibited increased contractility in the presence of endothelin-1 and larger basal mechanical tone in a unique assay developed to measure the contractile tone of the engineered valve tissues. This finding is important, because it implies that the functional properties of the valve are sensitive to EMT. Our results suggest that cyclic mechanical strain regulates EMT in a strain magnitude and directionally dependent manner.tight junctions | cytokines | activated myofibroblast C ardiac valves are sophisticated structures that function in a complex mechanical environment, opening and closing more than 3 billion times during the average human lifetime (1). Initially considered passive flaps of tissue, it is now acknowledged that valves contain a highly heterogeneous population of endothelial (VEC) and interstitial (VIC) cells. The VICs exist as synthetic, myofibroblast, or smooth muscle-like phenotypes (2, 3) and alter their tone in response to vasoactive mediators (4-7). The VECs line the surface of the valve leaflet and are unique in their ability to undergo endothelial-mesenchymal transformation (EMT), a process that is crucial for valvulogenesis (8, 9). Recent clinical evidence of EMT has been observed in pathologies such as ischemic cardiomyopathy and concomitant mitral regurgitation and is correlated with increased leaflet mechanical strains (10, 11). These pathological strains can be oriented obliquely to cell and tissue orientation (12, 13), suggesting the possible interaction between mechanical forces and tissue architecture in regulating EMT.Prior work has focused on the regulation of ...

show abstract

Fluid Dynamics of Heart Development

Cited by 62 publications

References 105 publications

Heartbeat-Driven Pericardiac Fluid Forces Contribute to Epicardium Morphogenesis

Heartbeat-Driven Pericardiac Fluid Forces Contribute to Epicardium Morphogenesis

Piezo1, a mechanically activated ion channel, is required for vascular development in mice

Cyclic strain induces dual-mode endothelial-mesenchymal transformation of the cardiac valve

Contact Info

Product

Resources

About