Targeted Mybpc3 Knock-Out Mice with Cardiac Hypertrophy Exhibit Structural Mitral Valve Abnormalities
Abstract
:1. Introduction
2. Experimental Section
3. Results and Discussion
3.1. Mybpc3 (−/−) Anterior Mitral Leaflet is Longer and Thicker than Wild-Type Anterior Mitral Leaflet by Echocardiographic Analysis
3.2. MicroCT Imaging Confirms the Results of Echocardiographic Imaging
Parameter | +/+ | +/− | −/− | p |
---|---|---|---|---|
N = 22 | N = 33 | N = 29 | ||
Length AML (mm) | 1.72 ± 0.08 | 1.73 ± 0.07 | 1.92 ± 0.08 | <0.001 * |
(1.64–1.94) | (1.55–1.90) | (1.80–2.09) | ||
Length PML (mm) | 1.36 ± 0.07 | 1.33 ± 0.07 | 1.35 ± 0.07 | NS * |
(1.23–1.46) | (1.20–1.45) | (1.23–1.51) | ||
Thickness AML + PML (mm) | 0.15 ± 0.02 | 0.18 ± 0.04 | 0.23 ± 0.04 | <0.001 * |
(0.11–0.18) | (0.10–0.19) | (0.14–0.29) | ||
LV Mass (mg) | 80 ± 16 | 88 ± 7 | 129 ± 26 | <0.0001 |
(55–109) | (71–105) | (99–173) | ||
EF (%) | 63 ± 5 | 62 ± 7 | 35 ± 7 | <0.0001 |
(55–76) | (52–80) | (22–49) | ||
ED Volume (mL) | 67 ± 11 | 63 ± 11 | 118 ± 40 | <0.0001 |
(43–88) | (39–89) | (42–175) |
3.3. Mybpc3-(−/−) Mitral Valve Leaflets Have Evidence of Increased TGFβ Signaling
3.4. Quantitative PCR Analysis Confirms Increased Expression of TGFβ-Related Genes in Myocardium
3.5. MV Leaflets in Human Non-Obstructive Hypertrophic Cardiomyopathy (HCM) Exhibit Increase in Collagen along with Molecular Changes in TGFβ Signaling
3.6. Discussion
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Judge, D.P.; Neamatalla, H.; Norris, R.A.; Levine, R.A.; Butcher, J.T.; Vignier, N.; Kang, K.H.; Nguyen, Q.; Bruneval, P.; Perier, M.-C.; et al. Targeted Mybpc3 Knock-Out Mice with Cardiac Hypertrophy Exhibit Structural Mitral Valve Abnormalities. J. Cardiovasc. Dev. Dis. 2015, 2, 48-65. https://doi.org/10.3390/jcdd2020048
Judge DP, Neamatalla H, Norris RA, Levine RA, Butcher JT, Vignier N, Kang KH, Nguyen Q, Bruneval P, Perier M-C, et al. Targeted Mybpc3 Knock-Out Mice with Cardiac Hypertrophy Exhibit Structural Mitral Valve Abnormalities. Journal of Cardiovascular Development and Disease. 2015; 2(2):48-65. https://doi.org/10.3390/jcdd2020048
Chicago/Turabian StyleJudge, Daniel P., Hany Neamatalla, Russell A. Norris, Robert A. Levine, Jonathan T. Butcher, Nicolas Vignier, Kevin H. Kang, Quangtung Nguyen, Patrick Bruneval, Marie-Cécile Perier, and et al. 2015. "Targeted Mybpc3 Knock-Out Mice with Cardiac Hypertrophy Exhibit Structural Mitral Valve Abnormalities" Journal of Cardiovascular Development and Disease 2, no. 2: 48-65. https://doi.org/10.3390/jcdd2020048