Vascular Smooth Muscle TRPV4 (Transient Receptor Potential Vanilloid Family Member 4) Channels Regulate Vasoconstriction and Blood Pressure in Obesity

Hypertension, Год журнала: 2023, Номер 80(4), С. 757 - 770

Опубликована: Фев. 16, 2023

Vascular endothelium and smooth muscle work together to keep the balance of vasomotor tone jointly maintain vascular homeostasis. Ca2+-permeable ion channel TRPV4 (transient receptor potential vanilloid family member 4) in endothelial cells regulates endothelium-dependent vasodilation contraction various states. However, how cell (TRPV4SMC) contributes function blood pressure regulation physiological pathologically obese condition has not been fully studied.We generated TRPV4-deficient mice developed diet-induced model analyzed role TRPV4SMC intracellular Ca2+ ([Ca2+]i) vasoconstriction. Vasomotor changes mouse mesenteric artery were measured by wire, myography. [Ca2+]i fluo-4 staining. Blood was recorded telemetric device.Vascular played different roles regulating than due their features regulation. Loss attenuated U46619- phenylephrine-induced contraction, suggesting its involvement contractility. Mesenteric arteries from showed SMC hyperplasia, an increased level TRPV4SMC. did influence development obesity but protected obesity-induced vasoconstriction hypertension. In deficient TRPV4, SMCs F-actin polymerization RhoA dephosphorylation under contractile stimuli. Moreover, SMC-dependent inhibited human resistance with inhibitor application.Our data identify as a regulator both states mice. ontogeny hypertension induced over-expression artery.

Язык: Английский

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

eLife, Год журнала: 2021, Номер 10

Опубликована: Сен. 7, 2021

Pannexin 1 (Panx1), an ATP-efflux pathway, has been linked with inflammation in pulmonary capillaries. However, the physiological roles of endothelial Panx1 vasculature are unknown. Endothelial transient receptor potential vanilloid 4 (TRPV4) channels lower artery (PA) contractility and exogenous ATP activates TRPV4 channels. We hypothesized that Panx1–ATP–TRPV4 channel signaling promotes vasodilation lowers arterial pressure (PAP). Endothelial, but not smooth muscle, knockout increased PA raised PAP mice. Flow/shear stress efflux through PAs. Panx1-effluxed extracellular signaled purinergic P2Y2 (P2Y2R) to activate protein kinase Cα (PKCα), which turn activated Finally, caveolin-1 provided a scaffold for Panx1, P2Y2R, PKCα, PAs, promoting their spatial proximity enabling interactions. These results indicate Panx1–P2Y2R–TRPV4 signaling, facilitated by caveolin-1, reduces

Язык: Английский

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Membrane cholesterol regulates TRPV4 function, cytoskeletal expression, and the cellular response to tension

Journal of Lipid Research, Год журнала: 2021, Номер 62, С. 100145 - 100145

Опубликована: Янв. 1, 2021

Despite the association of cholesterol with debilitating pressure-related diseases such as glaucoma, heart disease, and diabetes, its role in mechanotransduction is not well understood. We investigated relationship between mechanical strain, free membrane cholesterol, actin cytoskeleton, stretch-activated transient receptor potential vanilloid isoform 4 (TRPV4) channel human trabecular meshwork (TM) cells. Physiological levels cyclic stretch resulted time-dependent decreases cholesterol/phosphatidylcholine ratio upregulation stress fibers. Depleting m-β-cyclodextrin (MβCD) augmented TRPV4 activation by agonist GSK1016790A, swelling effects reversed supplementation. MβCD increased expression TRPV4, caveolin-1, flotillin. did colocalize or interact caveolae lipid rafts, apart from a truncated ∼75 kDa variant partially precipitated caveolin-1 antibody. induced currents TRPV4-expressing Xenopus laevis oocytes. Thus, regulates transduction information, channels mainly located outside cholesterol-enriched domains. Moreover, biomechanical milieu itself shapes content TM membranes. Diet, metabolism, might modulate conventional outflow pathway intraocular pressure glaucoma diabetes part modulating mechanosensing.

Язык: Английский

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Caveolar and non-Caveolar Caveolin-1 in ocular homeostasis and disease

Progress in Retinal and Eye Research, Год журнала: 2022, Номер 91, С. 101094 - 101094

Опубликована: Июнь 18, 2022

Язык: Английский

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Cracking the Endothelial Calcium (Ca2+) Code: A Matter of Timing and Spacing

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(23), С. 16765 - 16765

Опубликована: Ноя. 26, 2023

A monolayer of endothelial cells lines the innermost surface all blood vessels, thereby coming into close contact with every region body and perceiving signals deriving from both bloodstream parenchymal tissues. An increase in intracellular Ca2+ concentration ([Ca2+]i) is main mechanism whereby vascular integrate information conveyed by local circulating cues. Herein, we describe dynamics spatial distribution to understand how an array spatially restricted (at subcellular cellular levels) exploited intima fulfill this complex task. We then illustrate affect most appropriate function are integrated transmit more distant sites maintain cardiovascular homeostasis. Vasorelaxation sprouting angiogenesis were selected as example functions that finely tuned variable spatio-temporal profile signals. further highlighted distinct signatures regulate different phases vasculogenesis, i.e., proliferation migration, precursors.

Язык: Английский

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Loss of lung microvascular endothelial Piezo2 expression impairs NO synthesis, induces EndMT, and is associated with pulmonary hypertension

AJP Heart and Circulatory Physiology, Год журнала: 2022, Номер 323(5), С. H958 - H974

Опубликована: Сен. 23, 2022

The mechanosensory ion channel Piezo2 is exclusively expressed in lung microvascular endothelial cells (MVECs). Patient MVECs as well animal models of pulmonary (arterial) hypertension showed lower expression the lung. Mechanistically, required for calcium influx and NO production response to shear stress, whereas stimuli known induce mesenchymal transition (EndMT) reduce MVECs, knockdown induces a gene protein pattern consistent with EndMT.

Язык: Английский

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The role of endothelial TRP channels in age-related vascular cognitive impairment and dementia

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Март 20, 2023

Transient receptor potential (TRP) proteins are part of a superfamily polymodal cation channels that can be activated by mechanical, physical, and chemical stimuli. In the vascular endothelium, TRP regulate two fundamental parameters: membrane intracellular Ca 2+ concentration [(Ca ) i ]. widely expressed in cerebrovascular emerging as important mediators several brain microvascular functions (e.g., neurovascular coupling, endothelial function, blood–brain barrier permeability), which become impaired with aging. Aging is most significant risk factor for cognitive impairment (VCI), number individuals affected VCI expected to exponentially increase coming decades. Yet, there currently no preventative or therapeutic treatments available against development progression VCI. this review, we discuss involvement diverse physiological processes well pathogenesis age-related explore future neuroprotective strategies.

Язык: Английский

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Shexiang Baoxin Pill treats acute myocardial infarction by promoting angiogenesis via GDF15-TRPV4 signaling

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 165, С. 115186 - 115186

Опубликована: Июль 21, 2023

Angiogenesis has been considered a pivotal strategy for treating ischemic heart disease. One possible approach, the Shexiang Baoxin Pill (MUSKARDIA), noted to promote angiogenesis, but its underlying mechanism is still largely unknown. We aimed determine effects of MUSKARDIA on acute myocardial infarction (AMI), as well mechanistic bases. AMI was induced in rats, using left anterior descending coronary arterial occlusion, and either 6 (low) or 12 (high-dose) mg/kg/day administered 56 days. found that improved cardiac function counteracted against adverse remodeling among which most likely due it promoting angiogenesis. Transcriptome analysis by RNA-sequencing up-regulated pro-angiogenic genes, particularly growth differentiation factor 15 (GDF15), confirmed RT-qPCR. This up-regulation also correlated with elevated serum GDF15 levels. In vitro analyses human umbilical vein endothelial cells increased GDF15, stimulated MUSKARDIA, resulted enhanced cell migration, proliferation, tubular formation, all were reversed after knockdown lentiviral vector. Gene Ontology, Kyoto Genes Genomes enrichment identified calcium signaling pathway major contributor these outcomes, verified Western blot Cal-590 AM loading showing transient receptor potential cation channel subfamily V member 4 protein (TRPV4) intracellular Ca2+ levels accordance MUSKARDIA-induced up-regulation, decreased knock-down. Therefore, may exert cardioprotective via stimulating GDF15/TRPV4/calcium signaling/angiogenesis axis.

Язык: Английский

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The critical roles of caveolin-1 in lung diseases

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Сен. 24, 2024

Caveolin-1 (Cav-1), a structural and functional component in the caveolae, plays critical role transcytosis, endocytosis, signal transduction. Cav-1 has been implicated mediation of cellular processes by interacting with variety signaling molecules. is widely expressed endothelial cells, smooth muscle fibroblasts various organs, including lungs. The Cav-1-mediated internalization regulation molecules participate physiological pathological processes. Particularly, MAPK, NF-κB, TGFβ/Smad, eNOS/NO pathways have involved regulatory effects lung diseases. important on lungs indicate that can be potential target for treatment A scaffolding domain peptide CSP7 targeting developed. In this article, we mainly discuss structure its roles diseases, such as pneumonia, acute injury (ALI), asthma, chronic obstructive pulmonary disease (COPD), hypertension, fibrosis, cancer.

Язык: Английский

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Endothelial TRPV4 channels in lung edema and injury

Current topics in membranes, Год журнала: 2022, Номер unknown, С. 43 - 62

Опубликована: Янв. 1, 2022

Язык: Английский

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