Surface Strains in the Anterior Leaflet of the Functioning Mitral Valve

Sacks, Michael S.; He, Zhaoming; Baijens, L Lotte; Wanant, Sumanas; Shah, Parina; Sugimoto, H.; Yoganathan, A.P.

doi:10.1114/1.1529194

Cited by 135 publications

(150 citation statements)

References 34 publications

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“…VEC monolayers were subject to 0% (control), 10%, or 20% uniaxial cyclic strain at 1 Hz for 24 or 48 h using a custom-built cyclic stretcher device (Movies S1 and S2). The latter two strain magnitudes are representative of low-or high-strain regimes in mammalian cardiac valves (27,57). Cyclic strain was either applied parallel (termed "anisotropic") or orthogonal (termed "anisotropic-orthogonal") to initial tissue alignment, simulating healthy or diseased valves (12,13).…”

Section: Methodsmentioning

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

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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 ...

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Section: Methodsmentioning

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

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“…leaflet in vitro (14,22). Using a black tissue marking dye (Black Tissue Marking Dye, Thermoelectron, Pittsburgh, PA), a regular array of markers was placed on the ventricular surface of the AV leaflets.…”

Section: Methodsmentioning

confidence: 99%

Dynamic deformation characteristics of porcine aortic valve leaflet under normal and hypertensive conditions

Yap

Kim

Balachandran

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Calcific aortic valve (AV) disease has a high prevalence in the United States, and hypertension is correlated to early onset of the disease. The cause of the disease is poorly understood, although biological and remodeling responses to mechanical forces, such as membrane tension, have been hypothesized to play a role. The mechanical behavior of the native AV has, therefore, been the focus of many recent studies. In the present study, the dynamic deformation characteristics of the AV leaflet and the effects of hypertension on leaflet deformation are quantified. Whole porcine aortic roots were trimmed and mounted in an in vitro pulsatile flow loop and subjected to normal (80/120 mmHg), hypertensive (120/160 mmHg), or severe hypertensive (150/190 mmHg) conditions. Local valve leaflet deformations were calculated with dual-camera photogrammetry method: by tracking the motion of markers placed on the AV leaflets in three dimensions and calculating their spatial deformations. The results demonstrate that, first, during diastole, high transvalvular pressure induces a stretch waveform which plateaus over the diastolic duration in both circumferential and radial directions. During systole, the leaflet stretches in the radial direction due to forward flow drag forces but compresses in the circumferential direction in a manner in agreement with Poisson's effect. Second, average diastolic and systolic stretch ratios were quantified in the radial and circumferential directions in the base and belly region of the leaflet, and diastolic stretch was found to increase with increasing pressure conditions. dynamic stretch; dynamic strain; hypertension; dual-camera photogrammetry CALCIFIC AORTIC VALVE (AV) disease has a high prevalence, especially among the elderly (16). In the Unites States alone, AV disease is the third most common cardiovascular pathology and is a strong risk factor for other cardiac-related deaths (17,18,21). Every year, nearly 95,000 procedures are performed on the AV, making AV surgeries second only to the coronary bypass procedure (13,27). The number of patients requiring AV surgery is expected to triple by 2050 (34). A calcified AV has increased thickness, collagen fiber disarray, and deposition of calcium, and thus has a drastically reduced leaflet flexibility, disabling native valve kinematics and function, resulting in AV stenosis and/or regurgitation and heart failure (19).The majority of AV calcification has an idiopathic etiology. Recent studies have shown that AV sclerosis is an active process akin to atherosclerosis, involving lipoprotein deposition, chronic inflammation, and active leaflet calcification mediated by cell differentiation (11). Furthermore, in a manner similar to the correlation between adverse hemodynamic/mechanical environment and atherosclerosis formation (9, 10), data in the literature suggest that adverse mechanical forces may elicit pathological responses of AV leaflets. Isolated mechanical forces, including stretch, pressure, and fluid shear, have been shown to affect the remod...

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“…The center portion was used as it experiences the most homogenous strains during MV closure. 38 For the anchor strength study, posterior leaflets were used for testing. …”

Section: Tissue Preparationmentioning

confidence: 99%

Development of a Simultaneous Cryo-Anchoring and Radiofrequency Ablation Catheter for Percutaneous Treatment of Mitral Valve Prolapse

Boronyak

Merryman

2012

Ann Biomed Eng

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Surface Strains in the Anterior Leaflet of the Functioning Mitral Valve

Cited by 135 publications

References 34 publications

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

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

Dynamic deformation characteristics of porcine aortic valve leaflet under normal and hypertensive conditions

Development of a Simultaneous Cryo-Anchoring and Radiofrequency Ablation Catheter for Percutaneous Treatment of Mitral Valve Prolapse

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