4.6 Review

VASCULAR MECHANOTRANSDUCTION

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LAP2β transmits force to upregulate genes via chromatin domain stretching but not compression

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Summary: There is increasing evidence that force affects cells and tissues in various physiological and pathological processes, including gene regulation. However, the molecular pathway of force transmission from the nuclear lamina to the chromatin remains unclear. This study reveals that the nuclear protein LAP2 beta mediates force transmission from the nuclear lamina to the chromatin, and this pathway plays a crucial role in gene regulation.

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Role of TRPV4 channel in vasodilation and neovascularization

Miao Chen et al.

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Identification and Functional Analysis of Long Non-coding RNAs in Human Pulmonary Microvascular Endothelial Cells Subjected to Cyclic Stretch

Dong Wang et al.

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Effects of forces on chromatin

Kshitij Amar et al.

Summary: Chromatin, the unique structure of DNA and histone proteins in the cell nucleus, is the site where gene expression is dynamically regulated. Forces on chromatin, stemming from external and internal stresses, are known to modulate gene expression by affecting transcription factors. These forces act through both direct and indirect signaling pathways to regulate chromatin folding and deformation, ultimately impacting transcription.

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Shear-Regulated Extracellular Microenvironments and Endothelial Cell Surface Integrin Receptors Intertwine in Atherosclerosis

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FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Studying the Endothelial Glycocalyx in vitro: What Is Missing?

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Expression of Exogenous Epithelial Sodium Channel Beta Subunit in the Mouse Middle Cerebral Artery Increases Pressure-Induced Constriction

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Summary: This study demonstrates that expressing exogenous β-ENaC in isolated middle cerebral artery can enhance pressure-induced constriction (PIC) response, confirming the critical role of β-ENaC in PIC response. These findings provide evidence for further investigating whether inflammation-induced downregulation of β-ENaC contributes to cerebrovascular dysfunction.

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Spatial transcriptomics and proteomics technologies for deconvoluting the tumor microenvironment

Nan Wang et al.

Summary: The tumor microenvironment (TME) plays critical roles in tumorigenesis, metastasis, and drug resistance, making the deconvolution of TME essential for cancer research and treatment. Emerging spatial profiling technologies offer a powerful way to understand TME from multiple perspectives and are rapidly reshaping our understanding of the tumor microenvironment.

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The Entry and Egress of Monocytes in Atherosclerosis: A Biochemical and Biomechanical Driven Process

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Summary: According to the response to injury theory, monocytes entering the intima, taking up cholesterol and transforming into foam cells, and egress from plaques, are crucial for the progression of atherosclerosis. Various cytokines and receptors play roles in monocyte recruitment and egress, while neural guidance molecules and biomechanical factors are also important. Developing new therapies and investigating biochemical factors affecting monocyte migration will be beneficial for future studies.

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Cellular Crosstalk between Endothelial and Smooth Muscle Cells in Vascular Wall Remodeling

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Summary: Pathological vascular wall remodeling refers to the changes in structure and function of the vessel wall in response to injury, potentially leading to cardiovascular disease. Communication between endothelial cells and vascular smooth muscle cells is crucial for vasculature development and vessel homeostasis, with aberrant communication associated with various disease states including vascular wall remodeling. Different mechanisms such as paracrine regulations and direct contact play a role in this interplay.

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Calcium signaling mediates a biphasic mechanoadaptive response of endothelial cells to cyclic mechanical stretch

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Summary: This study identifies a biphasic response to cyclic stretch in endothelial monolayers, consisting of an initial calcium-driven junctional mechanoresponse, followed by mechanoadaptation facilitated by monolayer stiffening.

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The LINC complex is required for endothelial cell adhesion and adaptation to shear stress and cyclic stretch

Kevin B. Denis et al.

Summary: The LINC complex plays a crucial role in connecting the nucleus to the cytoskeleton and is essential for endothelial cell function and homeostasis. Disruption of the LINC complex through expression of DN-KASH results in impaired cell-cell and cell-matrix adhesion, barrier function, migration, and adaptation to mechanical forces.

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What Evolutionary Evidence Implies About the Identity of the Mechanoelectrical Couplers in Vascular Smooth Muscle Cells

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Summary: This review discusses the evolutionary role of these molecules in mechanosensing, limitations in identifying mechanosensitive molecules, and introduces a paradigm shifting molecular model for a VSMC mechanosensor. Loss of pressure-induced vasoconstriction can increase susceptibility to renal and cerebral vascular injury, with favored paradigms including transient receptor potential channels, integrins, and Degenerin channels as transducers.

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Mechanosensitive channel gating by delipidation

Vanessa Judith Flegler et al.

Summary: MscS channel opens when delipidated by detergents and closes after addition of detergent-solubilized lipids, supporting the model that lipid extrusion causes gating. The distribution of aliphatic chains during gating suggests that lipids leave the complex on the cytosolic side under high lateral tension, and flow into gaps on the periplasmic side.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Ih from synapses to networks: HCN channel functions and modulation in neurons

Crescent L. Combe et al.

Summary: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and their current I-h are widely distributed and have diverse functions in the central nervous system. The functions of HCN channels involve maintaining membrane potential and slow channel dynamics, playing roles in resonance, synaptic integration, transmitter release, plasticity, and other processes.

PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY (2021)

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Regulation of sinus node pacemaking and atrioventricular node conduction by HCN channels in health and disease

Mark R. Boyett et al.

Summary: This review summarizes the discovery of the funny current If in the heart several decades ago, as well as its important role in the sinus node and atrioventricular node. Studies have shown that the transcription and translation of Hcn genes play a crucial role in pacemaking in the sinus node and conduction in the atrioventricular node under normal physiological conditions and pathological states.

PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY (2021)

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The funny current: Even funnier than 40 years ago. Uncanonical expression and roles of HCN/f channels all over the body

Patrizia Benzoni et al.

Summary: The studies on the If current have revealed its novel functions in various systems and organs, such as sour taste transduction, hormone secretion, and cellular respiration. Additionally, it plays an important role in controlling stem cell cycle and bioelectrical signals.

PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY (2021)

Review Biochemistry & Molecular Biology

The funny current in genetically modified mice

Mattia L. DiFrancesco et al.

Summary: The hyperpolarization-activated funny current (I-f) has been extensively studied since its first description in 1979, with a focus on its role in cardiac pacemaker activity and modulation by the autonomic nervous system in rabbit and mouse models. Genetically modified mice have provided important insights into the mechanisms of cardiac pacemaker activity, particularly in understanding the role of I-f in intrinsic automaticity and heart rate regulation by the parasympathetic nervous system. The field benefits from advancements in in-vivo exploration techniques, imaging, genetics, and large-scale genomic approaches.

PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY (2021)

Review Cell Biology

Feeling the force: Multiscale force sensing and transduction at the cell-cell interface

Angus Inman et al.

Summary: Living cells have the ability to sense and respond to mechanical stimuli, which is crucial for many biological processes. The coordination of tissue-wide force transmission and local force sensing is necessary to regulate essential processes during development. Understanding how cells identify and interpret external forces, and integrate specific responses on cell and tissue level, remains a major challenge.

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY (2021)

Article Biology

Endothelial pannexin 1-TRPV4 channel signaling lowers pulmonary arterial pressure in mice

Zdravka Daneva et al.

Summary: The study showed that endothelial Panx1 signaling pathway contributes to vasodilation and reduces pulmonary arterial pressure through ATP-TRPV4 channel signaling. By regulating ATP efflux and TRPV4 channel activity, Panx1 could potentially be targeted for the treatment of pulmonary arterial hypertension and related diseases.

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Article Pharmacology & Pharmacy

Species-Specific Effects of Cation Channel TRPM4 Small-Molecule Inhibitors

Prakash Arullampalam et al.

Summary: The study reveals species-dependent differences in the response of TRPM4 inhibitors on human and mouse TRPM4 channels. While CBA and NBA can effectively inhibit human TRPM4, they may have different effects on mouse TRPM4. Furthermore, the application of 9-phenanthrol may lead to opposite outcomes for mouse TRPM4 depending on the site of application.

FRONTIERS IN PHARMACOLOGY (2021)

Review Physiology

Myogenic Tone in Peripheral Resistance Arteries and Arterioles: The Pressure Is On!

William F. Jackson

Summary: Resistance arteries and arterioles in the peripheral microcirculation play crucial roles in controlling blood pressure, blood flow distribution, and vascular resistance, with myogenic tone being a hallmark feature. However, our understanding of the signaling pathways underlying this key microvascular property remains incomplete, with emphasis on the roles of G-protein-coupled receptors, ion channels, and various kinases in the activity of vascular smooth muscle cells.

FRONTIERS IN PHYSIOLOGY (2021)

Review Physiology

The LINC Between Mechanical Forces and Chromatin

Olga Lityagina et al.

Summary: The heart's ability to sense and respond to mechanical stimuli is crucial for maintaining cardiac structure and function. Defects in mechanotransduction are linked to the development and progression of cardiovascular disease. The LINC complex plays a significant role in cardiovascular disease by transducing mechanical forces to chromatin.

FRONTIERS IN PHYSIOLOGY (2021)

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The Phenotypic Responses of Vascular Smooth Muscle Cells Exposed to Mechanical Cues

Lise Filt Jensen et al.

Summary: During the development and culture of vascular smooth muscle cells (SMCs), a shift in cell phenotype occurs due to the absence of physiological signals. Most studies have been conducted under standard culture conditions, neglecting the impact of ECM microenvironment and mechanical forces on SMCs.

CELLS (2021)

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Functions of Presynaptic Voltage-gated Calcium Channels

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Summary: This review discusses the biophysical properties of voltage-gated calcium channels present in presynaptic terminals and emphasizes their specialized properties for specific roles in mediating neurotransmitter release. It highlights how these channels participate in different patterns of presynaptic vesicular release based on their activation voltage threshold, kinetic properties, and voltage-dependence of inactivation.

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Nitric Oxide Signals Through IRAG to Inhibit TRPM4 Channels and Dilate Cerebral Arteries

Sher Ali et al.

Summary: This study reveals that nitric oxide induces vasodilation by inhibiting the activity of Ca2+-dependent TRPM4 cation channels in vascular smooth muscle cells. Further investigation showed that NO initiates a signaling cascade to block the release of Ca2+ from the sarcoplasmic reticulum, leading to the inhibition of TRPM4 activation. These findings provide insight into the essential molecular pathways of NO-induced vasodilation in cardiovascular physiology.

FUNCTION (2021)

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The epitranscriptome beyond m6A

David Wiener et al.

Summary: This Perspective reviews efforts to map six different RNA modifications and how they differ from N-6-methyladenosine. The authors discuss technical and analytical challenges of characterizing the epitranscriptome and provide their conclusions on the abundance and distribution of these modifications. The article highlights commonalities and differences among the modifications in comparison to m(6)A, speculating on their origins and functional abilities over evolutionary timescales.

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Article Biochemistry & Molecular Biology

Fast desensitization of acetylcholine receptors induced by a spider toxin

Na Clara Pan et al.

Summary: Nicotinic acetylcholine receptors (nAChRs) play crucial roles in regulating neuromuscular junction current, and a toxin called GsMTx4 has been shown to facilitate the desensitization of these receptors. It affects channel activity by prolonging the closing time, without influencing conductance or opening activity.

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Alveolar Stretch Activation of Endothelial Piezo1 Protects Adherens Junctions and Lung Vascular Barrier

Ming Zhong et al.

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LncRNA HOTAIR is a novel endothelial mechanosensitive gene

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Endothelial Glycocalyx Impairment in Disease Focus on Hyaluronan Shedding

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Differential expression of angiotensin II type 1 receptor subtypes within the cerebral microvasculature

Evan Yamasaki et al.

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