Validating the Paradigm That Biomechanical Forces Regulate Embryonic Cardiovascular Morphogenesis and Are Fundamental in the Etiology of Congenital Heart Disease
The goal of this review is to provide a broad overview of the biomechanical maturation and regulation of vertebrate cardiovascular (CV) morphogenesis and the evidence for mechanistic relationships between function and form relevant to the origins of congenital heart disease (CHD). The embryonic hear...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Journal of Cardiovascular Development and Disease |
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| Online Access: | https://www.mdpi.com/2308-3425/7/2/23 |
| _version_ | 1797565404249325568 |
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| author | Bradley B. Keller William J. Kowalski Joseph P. Tinney Kimimasa Tobita Norman Hu |
| author_facet | Bradley B. Keller William J. Kowalski Joseph P. Tinney Kimimasa Tobita Norman Hu |
| author_sort | Bradley B. Keller |
| collection | DOAJ |
| description | The goal of this review is to provide a broad overview of the biomechanical maturation and regulation of vertebrate cardiovascular (CV) morphogenesis and the evidence for mechanistic relationships between function and form relevant to the origins of congenital heart disease (CHD). The embryonic heart has been investigated for over a century, initially focusing on the chick embryo due to the opportunity to isolate and investigate myocardial electromechanical maturation, the ability to directly instrument and measure normal cardiac function, intervene to alter ventricular loading conditions, and then investigate changes in functional and structural maturation to deduce mechanism. The paradigm of “Develop and validate quantitative techniques, describe normal, perturb the system, describe abnormal, then deduce mechanisms” was taught to many young investigators by Dr. Edward B. Clark and then validated by a rapidly expanding number of teams dedicated to investigate CV morphogenesis, structure–function relationships, and pathogenic mechanisms of CHD. Pioneering studies using the chick embryo model rapidly expanded into a broad range of model systems, particularly the mouse and zebrafish, to investigate the interdependent genetic and biomechanical regulation of CV morphogenesis. Several central morphogenic themes have emerged. First, CV morphogenesis is inherently dependent upon the biomechanical forces that influence cell and tissue growth and remodeling. Second, embryonic CV systems dynamically adapt to changes in biomechanical loading conditions similar to mature systems. Third, biomechanical loading conditions dynamically impact and are regulated by genetic morphogenic systems. Fourth, advanced imaging techniques coupled with computational modeling provide novel insights to validate regulatory mechanisms. Finally, insights regarding the genetic and biomechanical regulation of CV morphogenesis and adaptation are relevant to current regenerative strategies for patients with CHD. |
| first_indexed | 2024-03-10T19:11:41Z |
| format | Article |
| id | doaj.art-0296e46f107042b69e3da795e7aaef07 |
| institution | Directory Open Access Journal |
| issn | 2308-3425 |
| language | English |
| last_indexed | 2024-03-10T19:11:41Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj.art-0296e46f107042b69e3da795e7aaef072023-11-20T03:40:49ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252020-06-01722310.3390/jcdd7020023Validating the Paradigm That Biomechanical Forces Regulate Embryonic Cardiovascular Morphogenesis and Are Fundamental in the Etiology of Congenital Heart DiseaseBradley B. Keller0William J. Kowalski1Joseph P. Tinney2Kimimasa Tobita3Norman Hu4Cincinnati Children’s Heart Institute, Greater Louisville and Western Kentucky Practice, Louisville, KY 40202, USALaboratory of Stem Cell and Neuro-Vascular Biology, Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USAKosair Charities Pediatric Heart Research Program, Cardiovascular Innovation Institute, University of Louisville, Louisville, KY 40202, USADepartment of Medical Affairs, Abiomed Japan K.K., Muromachi Higashi Mitsui Bldg, Tokyo 103-0022, JapanDepartment of Pediatrics, University of Utah, Salt Lake City, UT 84108, USAThe goal of this review is to provide a broad overview of the biomechanical maturation and regulation of vertebrate cardiovascular (CV) morphogenesis and the evidence for mechanistic relationships between function and form relevant to the origins of congenital heart disease (CHD). The embryonic heart has been investigated for over a century, initially focusing on the chick embryo due to the opportunity to isolate and investigate myocardial electromechanical maturation, the ability to directly instrument and measure normal cardiac function, intervene to alter ventricular loading conditions, and then investigate changes in functional and structural maturation to deduce mechanism. The paradigm of “Develop and validate quantitative techniques, describe normal, perturb the system, describe abnormal, then deduce mechanisms” was taught to many young investigators by Dr. Edward B. Clark and then validated by a rapidly expanding number of teams dedicated to investigate CV morphogenesis, structure–function relationships, and pathogenic mechanisms of CHD. Pioneering studies using the chick embryo model rapidly expanded into a broad range of model systems, particularly the mouse and zebrafish, to investigate the interdependent genetic and biomechanical regulation of CV morphogenesis. Several central morphogenic themes have emerged. First, CV morphogenesis is inherently dependent upon the biomechanical forces that influence cell and tissue growth and remodeling. Second, embryonic CV systems dynamically adapt to changes in biomechanical loading conditions similar to mature systems. Third, biomechanical loading conditions dynamically impact and are regulated by genetic morphogenic systems. Fourth, advanced imaging techniques coupled with computational modeling provide novel insights to validate regulatory mechanisms. Finally, insights regarding the genetic and biomechanical regulation of CV morphogenesis and adaptation are relevant to current regenerative strategies for patients with CHD.https://www.mdpi.com/2308-3425/7/2/23avian embryobiomechanicscardiovascular morphogenesiscomputational modelingcongenital heart diseasehemodynamics |
| spellingShingle | Bradley B. Keller William J. Kowalski Joseph P. Tinney Kimimasa Tobita Norman Hu Validating the Paradigm That Biomechanical Forces Regulate Embryonic Cardiovascular Morphogenesis and Are Fundamental in the Etiology of Congenital Heart Disease Journal of Cardiovascular Development and Disease avian embryo biomechanics cardiovascular morphogenesis computational modeling congenital heart disease hemodynamics |
| title | Validating the Paradigm That Biomechanical Forces Regulate Embryonic Cardiovascular Morphogenesis and Are Fundamental in the Etiology of Congenital Heart Disease |
| title_full | Validating the Paradigm That Biomechanical Forces Regulate Embryonic Cardiovascular Morphogenesis and Are Fundamental in the Etiology of Congenital Heart Disease |
| title_fullStr | Validating the Paradigm That Biomechanical Forces Regulate Embryonic Cardiovascular Morphogenesis and Are Fundamental in the Etiology of Congenital Heart Disease |
| title_full_unstemmed | Validating the Paradigm That Biomechanical Forces Regulate Embryonic Cardiovascular Morphogenesis and Are Fundamental in the Etiology of Congenital Heart Disease |
| title_short | Validating the Paradigm That Biomechanical Forces Regulate Embryonic Cardiovascular Morphogenesis and Are Fundamental in the Etiology of Congenital Heart Disease |
| title_sort | validating the paradigm that biomechanical forces regulate embryonic cardiovascular morphogenesis and are fundamental in the etiology of congenital heart disease |
| topic | avian embryo biomechanics cardiovascular morphogenesis computational modeling congenital heart disease hemodynamics |
| url | https://www.mdpi.com/2308-3425/7/2/23 |
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