Short-term angiotensin II treatment regulates cardiac nanomechanics<i>via</i>microtubule modifications

Swiatlowska, Pamela; Sanchez-Alonso, Jose L.; Mansfield, Catherine; Scaini, Denis; Korchev, Yuri; Novák, Pavel; Gorelik, Julia

doi:10.1039/d0nr02474k

Cited by 16 publications

(9 citation statements)

References 74 publications

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“…Long-term Ang II incubation up-regulates AT 2 R expression to induce downstream apoptosis signaling in iPSC-derived cardiomyocytes ( Gao J. et al, 2020 ). Whereas, short-term Ang II treatment reduces Young modulus in rat cardiomyocytes via AT 1 R. Inhibition using Rho-kinase or TGF-β1 abolished this effect ( Swiatlowska et al, 2020 ).…”

Section: Angiotensin II In Cardiovascular Systemmentioning

confidence: 99%

An Insight on Multicentric Signaling of Angiotensin II in Cardiovascular system: A Recent Update

et al. 2021

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The multifaceted nature of the renin-angiotensin system (RAS) makes it versatile due to its involvement in pathogenesis of the cardiovascular disease. Angiotensin II (Ang II), a multifaceted member of RAS family is known to have various potential effects. The knowledge of this peptide has immensely ameliorated after meticulous research for decades. Several studies have evidenced angiotensin I receptor (AT1 R) to mediate the majority Ang II-regulated functions in the system. Functional crosstalk between AT1 R mediated signal transduction cascades and other signaling pathways has been recognized. The review will provide an up-to-date information and recent discoveries involved in Ang II receptor signal transduction and their functional significance in the cardiovascular system for potential translation in therapeutics. Moreover, the review also focuses on the role of stem cell-based therapies in the cardiovascular system.

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Section: Angiotensin II In Cardiovascular Systemmentioning

confidence: 99%

An Insight on Multicentric Signaling of Angiotensin II in Cardiovascular system: A Recent Update

et al. 2021

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“…On the other hand, in cardiomyocytes from a load-deficient MI model, the tYM was reduced. Observed changes were due to an altered microtubular network that has also been shown to regulate the modified tYM in the Angiotensin II-treated adult rat cardiomyocytes (Swiatlowska et al 2020a ; Swiatlowska et al 2020b ). The high resolution and non-invasive nature of the contactless scanning mode are major benefits of this platform, suggesting great potential for expanding the use to other mechano-regulatory cell measurements.…”

Section: Cardiovascular Mechanosensing At the Nanoscale: From Single Molecules To Single Adhesionsmentioning

confidence: 94%

“…A non-contact, high-resolution mechano-scanning ion conductance microscopy (mechano-SICM) technique, measuring the transverse Young’s modulus (tYM) by a constant pressure application through a nanopipette was recently used to investigate specific membrane subdomains, enabled by the excellent resolution in all dimensions (Swiatlowska et al 2020a ; Swiatlowska et al 2020b ). When applying pressure, the probe’s vertical position is recorded, and a deformation map is generated from which the tYM can be calculated and corrected for the uneven geometry.…”

Section: Cardiovascular Mechanosensing At the Nanoscale: From Single Molecules To Single Adhesionsmentioning

confidence: 99%

Tools for studying and modulating (cardiac muscle) cell mechanics and mechanosensing across the scales

Swiatlowska

Iskratsch

2021

Biophys Rev

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Cardiomyocytes generate force for the contraction of the heart to pump blood into the lungs and body. At the same time, they are exquisitely tuned to the mechanical environment and react to e.g. changes in cell and extracellular matrix stiffness or altered stretching due to reduced ejection fraction in heart disease, by adapting their cytoskeleton, force generation and cell mechanics. Both mechanical sensing and cell mechanical adaptations are multiscale processes. Receptor interactions with the extracellular matrix at the nanoscale will lead to clustering of receptors and modification of the cytoskeleton. This in turn alters mechanosensing, force generation, cell and nuclear stiffness and viscoelasticity at the microscale. Further, this affects cell shape, orientation, maturation and tissue integration at the microscale to macroscale. A variety of tools have been developed and adapted to measure cardiomyocyte receptor-ligand interactions and forces or mechanics at the different ranges, resulting in a wealth of new information about cardiomyocyte mechanobiology. Here, we take stock at the different tools for exploring cardiomyocyte mechanosensing and cell mechanics at the different scales from the nanoscale to microscale and macroscale.

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“…The permutations of PTMs and tubulin isoforms is known as the “tubulin code” (S. Fig 1), which creates microtubule networks with distinct biochemical and mechanical properties. Altered detyrosination(Chen et al 2018; Yu et al 2021), acetylation(Swiatlowska et al 2020), and MAP(Cheng et al 2010; Li et al 2018; Yu et al 2021) binding are each implicated in pathological cardiac remodeling; yet how the tubulin code is rewritten during cardiac hypertrophy and HF remains largely unclear.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional, post-transcriptional, and post-translational mechanisms rewrite the tubulin code during cardiac hypertrophy and failure

Phyo

Uchida

Chen

et al. 2022

Preprint

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A proliferated and post-translationally modified microtubule network underlies cellular growth in cardiac hypertrophy and contributes to contractile dysfunction in heart failure. Yet how the heart achieves this modified network is poorly understood. Determining how the tubulin code - the permutations of tubulin isoforms and post-translational modifications - is rewritten upon cardiac stress may provide new targets to modulate cardiac remodeling. Further, while tubulin can autoregulate its own expression, it is unknown if autoregulation is operant in the heart or tuned in response to stress. Here we use heart failure patient samples and murine models of cardiac remodeling to interrogate transcriptional, autoregulatory, and post-translational mechanisms that contribute to microtubule network remodeling at different stages of heart disease. We find that autoregulation is operant across tubulin isoforms in the heart and leads to an apparent disconnect in tubulin mRNA and protein levels in heart failure. We also find that within 4 hours of a hypertrophic stimulus and prior to cardiac growth, microtubule detyrosination is rapidly induced to help stabilize the network. This occurs concomitant with rapid transcriptional and autoregulatory activation of specific tubulin isoforms and microtubule motors. Upon continued hypertrophic stimulation, there is an increase in post-translationally modified microtubule tracks and anterograde motors to support cardiac growth, while total tubulin content increases through progressive transcriptional and autoregulatory induction of tubulin isoforms. Our work provides a new model for how the tubulin code is rapidly rewritten to establish a proliferated, stable microtubule network that drives cardiac remodeling, and provides the first evidence of tunable tubulin autoregulation during pathological progression.

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Short-term angiotensin II treatment regulates cardiac nanomechanicsviamicrotubule modifications

Abstract: MechanoSICM is used to understand the role of angiotensin II on transverse Young's modulus at the nanoscale level.

Cited by 16 publications

References 74 publications

An Insight on Multicentric Signaling of Angiotensin II in Cardiovascular system: A Recent Update

An Insight on Multicentric Signaling of Angiotensin II in Cardiovascular system: A Recent Update

Tools for studying and modulating (cardiac muscle) cell mechanics and mechanosensing across the scales

Transcriptional, post-transcriptional, and post-translational mechanisms rewrite the tubulin code during cardiac hypertrophy and failure

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