Regulation of cardiomyocyte t-tubule structure by preload and afterload: Roles in cardiac compensation and decompensation.

Autor:	Ruud M; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo, Norway., Frisk M; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo, Norway., Melleby AO; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo, Norway., Norseng PA; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo, Norway., Mohamed BA; Department of Cardiology and Pneumology, Georg-August-University, Göttingen, Germany., Li J; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo, Norway., Aronsen JM; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway., Setterberg IE; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo, Norway., Jakubiczka J; Department of Cardiology and Pneumology, Georg-August-University, Göttingen, Germany., van Hout I; Department of Physiology, School of Biomedical Sciences and HeartOtago, University of Otago, Dunedin, New Zealand., Coffey S; Department of Medicine and HeartOtago, Dunedin School of Medicine, Dunedin Hospital, Dunedin, New Zealand., Shen X; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo, Norway., Nygård S; Department of Informatics, University of Oslo, Oslo, Norway., Lunde IG; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo, Norway., Tønnessen T; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo, Norway.; Department of Cardiothoracic Surgery, Oslo University Hospital, Oslo, Norway., Jones PP; Department of Physiology, School of Biomedical Sciences and HeartOtago, University of Otago, Dunedin, New Zealand., Sjaastad I; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo, Norway., Gullestad L; Department of Cardiology, Oslo University Hospital, Oslo, Norway., Toischer K; Department of Cardiology and Pneumology, Georg-August-University, Göttingen, Germany., Dahl CP; Department of Cardiology, Oslo University Hospital, Oslo, Norway., Christensen G; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo, Norway., Louch WE; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.; K.G. Jebsen Centre for Cardiac Research, University of Oslo, Oslo, Norway.
Jazyk:	angličtina
Zdroj:	The Journal of physiology [J Physiol] 2024 Sep; Vol. 602 (18), pp. 4487-4510. Date of Electronic Publication: 2024 Apr 30.
DOI:	10.1113/JP284566
Abstrakt:	Mechanical load is a potent regulator of cardiac structure and function. Although high workload during heart failure is associated with disruption of cardiomyocyte t-tubules and Ca 2+ homeostasis, it remains unclear whether changes in preload and afterload may promote adaptive t-tubule remodelling. We examined this issue by first investigating isolated effects of stepwise increases in load in cultured rat papillary muscles. Both preload and afterload increases produced a biphasic response, with the highest t-tubule densities observed at moderate loads, whereas excessively low and high loads resulted in low t-tubule levels. To determine the baseline position of the heart on this bell-shaped curve, mice were subjected to mildly elevated preload or afterload (1 week of aortic shunt or banding). Both interventions resulted in compensated cardiac function linked to increased t-tubule density, consistent with ascension up the rising limb of the curve. Similar t-tubule proliferation was observed in human patients with moderately increased preload or afterload (mitral valve regurgitation, aortic stenosis). T-tubule growth was associated with larger Ca 2+ transients, linked to upregulation of L-type Ca 2+ channels, Na + -Ca 2+ exchanger, mechanosensors and regulators of t-tubule structure. By contrast, marked elevation of cardiac load in rodents and patients advanced the heart down the declining limb of the t-tubule-load relationship. This bell-shaped relationship was lost in the absence of electrical stimulation, indicating a key role of systolic stress in controlling t-tubule plasticity. In conclusion, modest augmentation of workload promotes compensatory increases in t-tubule density and Ca 2+ cycling, whereas this adaptation is reversed in overloaded hearts during heart failure progression. KEY POINTS: Excised papillary muscle experiments demonstrated a bell-shaped relationship between cardiomyocyte t-tubule density and workload (preload or afterload), which was only present when muscles were electrically stimulated. The in vivo heart at baseline is positioned on the rising phase of this curve because moderate increases in preload (mice with brief aortic shunt surgery, patients with mitral valve regurgitation) resulted in t-tubule growth. Moderate increases in afterload (mice and patients with mild aortic banding/stenosis) similarly increased t-tubule density. T-tubule proliferation was associated with larger Ca 2+ transients, with upregulation of the L-type Ca 2+ channel, Na + -Ca 2+ exchanger, mechanosensors and regulators of t-tubule structure. By contrast, marked elevation of cardiac load in rodents and patients placed the heart on the declining phase of the t-tubule-load relationship, promoting heart failure progression. The dependence of t-tubule structure on preload and afterload thus enables both compensatory and maladaptive remodelling, in rodents and humans. (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)
Databáze:	MEDLINE
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