Microtubules Modulate the Stiffness of Cardiomyocytes Against Shear Stress

Nishimura, Satoshi; Nagai, Shinya; Katoh, Masakazu; Yamashita, Hiroshi; Saeki, Yasutake; Okada, Junichi; Hisada, Toshiaki; Nagai, Ryozo; Sugiura, Seiryo

doi:10.1161/01.res.0000197785.51819.e8

Cited by 91 publications

(72 citation statements)

References 43 publications

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“…We showed that the transverse stiffness in cardiomyocytes from hearts with ISO-induced hypertrophy was reduced by cross-bridge inhibition (actin-myosin interaction) using BDM and blebbistatin. Thus, the present results indicate that longitudinal shear stiffness is increased by polymerization of microtubules 42 and that transverse (indentation) stiffness is also increased by residual cross-bridge formation under pathological conditions. It remains unclear which direction of stiffness contributes to deterioration of diastolic function.…”

supporting

confidence: 57%

“…Nishimura et al succeeded in measuring multiple aspects of the mechanical properties of single cardiomyocytes from normal rat hearts, including tensile stiffness, transverse (indentation) stiffness, and shear stiffness in both the transverse and longitudinal planes. 42 Of all the measurements, only the stiffness against shear in the longitudinal plane of normal cardiomyocytes was modulated by the microtubule cytoskeleton. For pathological conditions, they measured longitudinal shear stiffness in myocytes from a hamster model of cardiomyopathy.…”

mentioning

confidence: 99%

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Increased Passive Stiffness of Cardiomyocytes in the Transverse Direction and Residual Actin and Myosin Cross-Bridge Formation in Hypertrophied Rat Hearts Induced by Chronic β-Adrenergic Stimulation

Yoshikawa

Nakamura

Miura

et al. 2013

Circ J

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supporting

confidence: 57%

mentioning

confidence: 99%

Increased Passive Stiffness of Cardiomyocytes in the Transverse Direction and Residual Actin and Myosin Cross-Bridge Formation in Hypertrophied Rat Hearts Induced by Chronic β-Adrenergic Stimulation

Yoshikawa

Nakamura

Miura

et al. 2013

Circ J

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“…In contrast, in AVCMs and skeletal muscle fibers, mitochondria are spatially confined to the space among the myofilaments and have no opportunity to move toward distant mitochondria. This might account for the lower frequency of fusion events seen in cultured AVCMs and other differentiated muscle paradigms (17,45). In addition to the structural confinement of mitochondria, in vivo and cell culture conditions seem to affect mitochondrial motility differently, with mitochondria showing little movement in freshly isolated striated and vascular smooth muscle but vigorous displacement in proliferating cultured striated and smooth muscle cells (17,46).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial fusion dynamics is robust in the heart and depends on calcium oscillations and contractile activity

Eisner

Cupo

Gao

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Mitochondrial fusion is thought to be important for supporting cardiac contractility, but is hardly detectable in cultured cardiomyocytes and is difficult to directly evaluate in the heart. We overcame this obstacle through in vivo adenoviral transduction with matrix-targeted photoactivatable GFP and confocal microscopy. Imaging in whole rat hearts indicated mitochondrial network formation and fusion activity in ventricular cardiomyocytes. Promptly after isolation, cardiomyocytes showed extensive mitochondrial connectivity and fusion, which decayed in culture (at 24-48 h). Fusion manifested both as rapid content mixing events between adjacent organelles and slower events between both neighboring and distant mitochondria. Loss of fusion in culture likely results from the decline in calcium oscillations/contractile activity and mitofusin 1 (Mfn1), because (i) verapamil suppressed both contraction and mitochondrial fusion, (ii) after spontaneous contraction or short-term field stimulation fusion activity increased in cardiomyocytes, and (iii) ryanodine receptor-2-mediated calcium oscillations increased fusion activity in HEK293 cells and complementing changes occurred in Mfn1. Weakened cardiac contractility in vivo in alcoholic animals is also associated with depressed mitochondrial fusion. Thus, attenuated mitochondrial fusion might contribute to the pathogenesis of cardiomyopathy.ardiac contractions require a constant energy supply, which is provided by mitochondrial metabolism. ATP is needed for excitation-contraction coupling (ECC) for both contraction and relaxation in each cycle (1, 2). ECC-associated cytoplasmic Ca 2+ transients ([Ca 2+ ] c ) are propagated to the mitochondrial matrix (3) to regulate Ca 2+ -dependent mitochondrial dehydrogenases, ATP synthesis, and intracellular Ca 2+ homeostasis (4). Thus, cardiac mitochondria are forced to work permanently and likely require quality control mechanisms to keep them in a functioning state.In many tissues, mitochondria are permanently rebuilt through evolutionarily conserved cyclic processes of fusion and fission. Fusion involves content exchange, allowing complementation of mitochondrial solutes, proteins, and DNA. Fission allows segregation of damaged components (5, 6). Both fusion and fission are promoted by mitochondrial movements that can bring distant mitochondria close to one another and can also separate interacting structures (7). However, the spatial arrangements and mitochondrial morphology are determined by sarcomers in ventricular myocytes, the contractile units of the adult mammalian heart. The gaps among densely packed parallel myofibrils are inhabited by bullet-like mitochondria that run longitudinally, interacting intimately with the junctional sarcoplasmic reticulum (SR), in a conformation that facilitates Ca 2+ exchange and supports ECC (4,8). Despite the spatial restrictions intrinsic to adult cardiomyocyte mitochondria, interactions among these organelles have been proposed based on functional observations. Reactive oxygen species (ROS)...

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“…In cardiomyocytes microtubules play a role in resisting shear stress (Nishimura et al, 2006) and are important in modulating the progression of cardiac hypertrophy (Cooper, 2006). Thus it is tempting to speculate that INF1 may also play a role in these processes.…”

Section: Discussionmentioning

confidence: 99%