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Chronic stretch of engineered heart tissue induces hypertrophy and functional improvement
Author(s) -
Fink Christine,
Ergün Süleman,
Kralisch Dirk,
Remmers Ute,
Weil Joachim,
Eschenhagen Thomas
Publication year - 2000
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.14.5.669
Subject(s) - myocyte , myofilament , muscle hypertrophy , contraction (grammar) , medicine , cardiac myocyte , isoprenaline , isometric exercise , chemistry , stimulation , endocrinology , cardiac hypertrophy , anatomy , biophysics , biology
To examine the influence of chronic mechanical stretch on functional behavior of cardiac myocytes, we reconstituted embryonic chick or neonatal rat cardiac myocytes to a 3‐dimensional engineered heart tissue (EHT) by mixing freshly isolated cells with neutralized collagen I and culturing them between two Velcro‐coated silicone tubes, held at a fixed distance with a metal spacer. After 4 days, EHTs were subjected to a phasic unidirectional stretch for 6 days in serum‐containing medium. Compared to unstretched controls, RNA/DNA and protein/cell ratios increased by 100% and 50%, respectively. ANF mRNA and a‐sarcomeric actin increased by 98% and 40%, respectively. Morphologically, stretched EHTs exhibited improved organization of cardiac myocytes into parallel arrays of rod‐shaped cells, increased cell length and width, longer myofilaments, and increased mitochondrial density. Thus, stretch induced phenotypic changes, generally referred to as hypertrophy. Concomitantly, force of contraction was two‐ to fourfold higher both under basal conditions and after stimulation with calcium or the β‐adrenergic agonist isoprenaline. Contraction kinetics were accelerated with a 14–44% decrease in twitch duration under all those conditions. In summary, we have developed a new in vitro model that allows morphological, molecular, and functional consequences of stretch to be studied under defined conditions. The main finding was that stretch of EHTs induced cardiac myocyte hypertrophy, which was accompanied by marked improvement of contractile function.—Fink, C., Ergün, S., Kralisch, D., Remmers, U., Weil, J., Eschenhagen, T. Chronic stretch of engineered heart tissue induces hypertrophy and functional improvement. FASEB J. 14, 669–679 (2000)