Mechanotransduction in Cardiac Hypertrophy and Failure

Circulation Research, Journal Year: 2015, Volume and Issue: 116(8), P. 1462 - 1476

Published: April 9, 2015

Cardiac muscle cells have an intrinsic ability to sense and respond mechanical load through a process known as mechanotransduction. In the heart, this involves conversion of stimuli into biochemical events that induce changes in myocardial structure function. Mechanotransduction its downstream effects function initially adaptive responses serve compensatory mechanisms during adaptation initial load. However, under prolonged abnormal loading conditions, remodeling processes can become maladaptive, leading altered physiological development pathological cardiac hypertrophy heart failure. Although underlying mechanotransduction are far from being fully elucidated, human mouse genetic studies highlighted various cytoskeletal sarcolemmal structures myocytes likely candidates for transducers, based on their link signaling molecules architectural components important disease pathogenesis. review, we summarize recent developments uncovered specific protein complexes linked mechanotransmission within sarcomere, intercalated disc, at sarcolemma. The acting mechanotransducers first step drives remodeling, well transition failure, may provide better insights driving mechanotransduction-based diseases.

Language: Английский

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Identifying Pathophysiological Mechanisms in Heart Failure With Reduced Versus Preserved Ejection Fraction

Journal of the American College of Cardiology, Journal Year: 2018, Volume and Issue: 72(10), P. 1081 - 1090

Published: Aug. 28, 2018

Language: Английский

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Extracellular Matrix–Mediated Maturation of Human Pluripotent Stem Cell–Derived Cardiac Monolayer Structure and Electrophysiological Function

Circulation Arrhythmia and Electrophysiology, Journal Year: 2016, Volume and Issue: 9(4)

Published: April 1, 2016

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) monolayers generated to date display an immature embryonic-like functional and structural phenotype that limits their utility for research cardiac regeneration. In particular, the electrophysiological function of hPSC-CM bioengineered constructs used are characterized by slow electric impulse propagation velocity action potential profiles.Here, we have identified optimal extracellular matrix significant maturation monolayers. plated in combination velocities ≈2× faster than previously reported (43.6±7.0 cm/s; n=9) mature cardiomyocyte profiles, including hyperpolarized diastolic rapid upstroke (146.5±17.7 V/s; n=5 monolayers). addition, promoted hypertrophic growth expression key sarcolemmal (SCN5A, Kir2.1, connexin43) myofilament markers (cardiac troponin I). The process here relies on activation integrin signaling pathways: neutralization β1 receptors via blocking antibodies pharmacological blockade focal adhesion kinase prevented maturation.Maturation human is achieved a 1-week period plating PDMS (polydimethylsiloxane) coverslips rather conventional 2-dimensional cell culture formats, such as glass or plastic dishes. Activation essential

Language: Английский

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Analysis of cardiac magnetic resonance imaging in 36,000 individuals yields genetic insights into dilated cardiomyopathy

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: May 7, 2020

Abstract Dilated cardiomyopathy (DCM) is an important cause of heart failure and the leading indication for transplantation. Many rare genetic variants have been associated with DCM, but common variant studies disease yielded few loci. As structural changes in are a defining feature we report genome-wide association study cardiac magnetic resonance imaging (MRI)-derived left ventricular measurements 36,041 UK Biobank participants, replication 2184 participants from Multi-Ethnic Study Atherosclerosis. We identify 45 previously unreported loci structure function, many near well-established genes Mendelian cardiomyopathies. A polygenic score MRI-derived end systolic volume strongly associates incident DCM general population. Even among carriers TTN truncating mutations, this influences size function human heart. These results further implicate polymorphisms pathogenesis DCM.

Language: Английский

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Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 31, 2023

Abstract Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical regarding cell activities and metabolism. Typical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, viscosity. Mechanotransduction has been expected trigger multiple such as embryonic development, repair regeneration. However, prolonged excessive stimulation can result pathological multi-organ fibrosis, tumorigenesis, cancer immunotherapy resistance. Although associations between normal homeostasis diseases have identified, regulatory mechanisms among different are not yet comprehensively illustrated, no effective therapies currently available targeting cue-related signaling. This review systematically summarizes characteristics typical conditions with updated evidence. The key effectors responding stimulations listed, Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator PDZ-binding motif (TAZ), transient receptor potential vanilloid 4 (TRPV4). We also reviewed signaling pathways, therapeutic targets cutting-edge clinical applications related cues.

Language: Английский

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Mechanical regulation of gene expression in cardiac myocytes and fibroblasts

Nature Reviews Cardiology, Journal Year: 2019, Volume and Issue: 16(6), P. 361 - 378

Published: Jan. 25, 2019

Language: Английский

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Nanotopography-Induced Structural Anisotropy and Sarcomere Development in Human Cardiomyocytes Derived from Induced Pluripotent Stem Cells

ACS Applied Materials & Interfaces, Journal Year: 2016, Volume and Issue: 8(34), P. 21923 - 21932

Published: Feb. 11, 2016

Understanding the phenotypic development of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is a prerequisite to advancing regenerative cardiac therapy, disease modeling, and drug screening applications. Lack consistent hiPSC-CM in vitro data can be largely attributed inability conventional culture methods mimic structural, biochemical, mechanical aspects myocardial niche accurately. Here, we present nanogrid array comprised nanogrooved topographies, with groove widths ranging from 350 2000 nm, study effect different nanoscale structures on structural hiPSC-CMs vitro. Nanotopographies were designed have biomimetic interface, based observations oriented extracellular matrix (ECM) fibers found vivo. Nanotopographic substrates integrated self-assembling chimeric peptide containing Arg-Gly-Asp (RGD) cell adhesion motif. Using this platform, peptide-coated was comparable that fibronectin-coated surfaces. Cardiomyocyte organization dependent nanotopographical feature size biphasic manner, improved achieved grooves 700-1000 nm range. These findings highlight capability surface-functionalized, bioinspired influence cardiomyocyte development, capacity for such platforms serve as versatile assay investigating role topographical guidance cues behavior. Such could potentially create more physiologically relevant tissues future modeling studies.

Language: Английский

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Bearing My Heart: The Role of Extracellular Matrix on Cardiac Development, Homeostasis, and Injury Response

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 8

Published: Jan. 12, 2021

The extracellular matrix (ECM) is an essential component of the heart that imparts fundamental cellular processes during organ development and homeostasis. Most cardiovascular diseases involve severe remodeling ECM, culminating in formation fibrotic tissue deleterious to function. Treatment schemes effective at managing fibrosis promoting physiological ECM repair are not yet reach. Of note, composition cardiac changes significantly a short period after birth, concurrent with loss regenerative capacity heart. This highlights importance understanding function headed for more efficient therapies. In this review, we explore impact alterations, throughout ontogeny disease, on cells debate available approaches deeper insights cell-ECM interactions, toward design new

Language: Английский

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Electrically Conductive Collagen‐PEDOT:PSS Hydrogel Prevents Post‐Infarct Cardiac Arrhythmia and Supports hiPSC‐Cardiomyocyte Function

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(28)

Published: April 23, 2024

Abstract Myocardial infarction (MI) causes cell death, disrupts electrical activity, triggers arrhythmia, and results in heart failure, whereby 50–60% of MI‐associated deaths manifest as sudden cardiac (SCD). The most effective therapy for SCD prevention is implantable cardioverter defibrillators (ICDs). However, ICDs contribute to adverse remodeling disease progression do not prevent arrhythmia. This work develops an injectable collagen‐PEDOT:PSS (poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate) hydrogel that protects infarcted hearts against ventricular tachycardia (VT) can be combined with human induced pluripotent stem (hiPSC)‐cardiomyocytes promote partial remuscularization. PEDOT:PSS improves collagen gel formation, micromorphology, conductivity. hiPSC‐cardiomyocytes hydrogels exhibit near‐adult sarcomeric length, improved contractility, enhanced calcium handling, conduction velocity. RNA‐sequencing data indicate maturation cell‐matrix interactions. Injecting mouse decreases VT the levels healthy hearts. Collectively, offer a versatile platform treating injuries.

Language: Английский

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Molecular Regulation of Cardiomyocyte Maturation

Current Cardiology Reports, Journal Year: 2025, Volume and Issue: 27(1)

Published: Jan. 21, 2025

Language: Английский

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