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Research Papers

Cyclic Pressure and Angiotensin II Influence the Biomechanical Properties of Aortic Valves

[+] Author and Article Information
Valtresa Myles

e-mail: Myles.val@gmail.com

Jun Liao

e-mail: jliao@abe.msstate.edu

James N. Warnock

e-mail: jwarnock@abe.msstate.edu
Department of Agricultural
and Biological Engineering,
Mississippi State University,
Mississippi State, MS 39762

Contributed by the Bioengineering Division of ASME for publication in the JOURNAL OF BIOMECHANICAL ENGINEERING. Manuscript received June 20, 2013; final manuscript received November 11, 2013; accepted manuscript posted November 15, 2013; published online December 4, 2013. Assoc. Editor: Guy M. Genin.

J Biomech Eng 136(1), 011011 (Dec 04, 2013) (8 pages) Paper No: BIO-13-1272; doi: 10.1115/1.4026041 History: Received June 20, 2013; Revised November 11, 2013; Accepted November 15, 2013

Hypertension is a known risk factor for aortic stenosis. The elevated blood pressure increases the transvalvular load and can elicit inflammation and extracellular matrix (ECM) remodeling. Elevated cyclic pressure and the vasoactive agent angiotensin II (Ang II) both promote collagen synthesis, an early hallmark of aortic sclerosis. In the current study, it was hypothesized that elevated cyclic pressure and/or angiotensin II decreases extensibility of aortic valve leaflets due to an increase in collagen content and/or interstitial cell stiffness. Porcine aortic valve leaflets were exposed to pressure conditions of increasing magnitude (static atmospheric pressure, 80, and 120 mmHg) with and without 10−6 M Ang II. Biaxial mechanical testing was performed to determine extensibility in the circumferential and radial directions and collagen content was determined using a quantitative dye-binding method at 24 and 48 h. Isolated aortic valve interstitial cells exposed to the same experimental conditions were subjected to atomic force microscopy to assess cellular stiffness at 24 h. Leaflet tissue incubated with Ang II decreased tissue extensibility in the radial direction, but not in the circumferential direction. Elevated cyclic pressure decreased extensibility in both the radial and circumferential directions. Ang II and elevated cyclic pressure both increased the collagen content in leaflet tissue. Interstitial cells incubated with Ang II were stiffer than those incubated without Ang II while elevated cyclic pressure caused a decrease in cell stiffness. The results of the current study demonstrated that both pressure and Ang II play a role in altering the biomechanical properties of aortic valve leaflets. Ang II and elevated cyclic pressure decreased the extensibility of aortic valve leaflet tissue. Ang II induced direction specific changes in extensibility, demonstrating different response mechanisms. These findings help to provide a better understanding of the responses of aortic valves to mechanical and biochemical changes that occur under hypertensive conditions.

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Figures

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Fig. 1

Pressure system schematic. *Average temperature inside the pressure chamber, 35.9 °C.

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Fig. 2

Dissection of aortic valve leaflet used for biaxial testing including fiducial marker placement

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Fig. 3

Representative tension versus stretch curve obtained from porcine aortic valve leaflet tissue

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Fig. 4

Peak stretch of aortic valve leaflet tissue in each experimental group at 24 h time point. (A) Circumferential direction. (B) Radial direction. Error bars represent standard deviation (n = 6). * denotes a significant difference (p < 0.05) when compared to the experimental group in the circumferential direction (A) and groups 1 and 2 in the radial direction (B). # denotes a significant difference (p < 0.05) between experimental groups incubated with and without Ang II. Experimental group 1: 0 mmHg, −ve Ang II; experimental group 2: 80 mmHg, −ve Ang II; experimental group 3: 120 mmHg, −ve Ang II; experimental group 4: 0 mmHg, +ve Ang II; experimental group 5: 80 mmHg, +ve Ang II; experimental group 6: 120 mmHg, +ve Ang II. Leaflets exposed to experimental groups for 24 h did not significantly differ from those at the 48 h time point.

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Fig. 5

Collagen content of aortic valve leaflet tissue in each experimental group at the 24 h time point. Error bars represent standard deviation (n = 6). * denotes a significant difference (p < 0.05) when compared to experimental groups 1 and 2. ^ denotes a significant difference (p < 0.05) when compared to the same experimental group at 48 h. # denotes a significant difference (p < 0.05) between experimental groups incubated with and without Ang II. Experimental group 1: 0 mmHg, −ve Ang II; experimental group 2: 80 mmHg, −ve Ang II; experimental group 3: 120 mmHg, −ve Ang II; experimental group 4: 0 mmHg, +ve Ang II; experimental group 5: 80 mmHg, +ve Ang II; experimental group 6: 120 mmHg, +ve Ang II.

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Fig. 6

Young's moduli of aortic valve interstitial cells in each experimental group at 24 h. Error bars represent standard deviation (n = 7). * denotes a significant difference (p < 0.05) when compared to experimental groups 1, 2, 4, and 6. ^ denotes a significant difference (p < 0.05) when compared to all other experimental groups. # denotes a significant difference (p < 0.05) between experimental groups incubated with and without Ang II. Experimental group 1: 0 mmHg, −ve Ang II; experimental group 2: 80 mmHg, −ve Ang II; experimental group 3: 120 mmHg, −ve Ang II; experimental group 4: 0 mmHg, +ve Ang II; experimental group 5: 80 mmHg, +ve Ang II; experimental group 6: 120 mmHg, +ve Ang II.

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