490 results match your criteria trpc4


TRPC channel-derived calcium fluxes differentially regulate ATP and flow-induced activation of eNOS.

Nitric Oxide 2021 Apr 1;111-112:1-13. Epub 2021 Apr 1.

School of Biomedical Engineering, Science, and Health Systems, Drexel University, 3141 Market St., Philadelphia, PA, 19104, USA. Electronic address:

Endothelial dysfunction, characterised by impaired nitric oxide (NO) bioavailability, arises in response to a variety of cardiovascular risk factors and precedes atherosclerosis. NO is produced by tight regulation of endothelial nitric oxide synthase (eNOS) activity in response to vasodilatory stimuli. This regulation of eNOS is mediated in part by store-operated calcium entry (SOCE). Read More

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Canonical transient receptor potential channels and their modulators: biology, pharmacology and therapeutic potentials.

Arch Pharm Res 2021 Mar 24. Epub 2021 Mar 24.

Department of Pharmacology and Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, China.

Canonical transient receptor potential channels (TRPCs) are nonselective, high calcium permeability cationic channels. The TRPCs family includes TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7. These channels are widely expressed in the cardiovascular and nervous systems and exist in many other human tissues and cell types, playing several crucial roles in the human physiological and pathological processes. Read More

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Expression of canonical transient receptor potential channels in U-2 OS and MNNG-HOS osteosarcoma cell lines.

Oncol Lett 2021 Apr 21;21(4):307. Epub 2021 Feb 21.

Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, D-17475 Greifswald, Germany.

In U-2 OS and MNNG-HOS osteosarcoma cells, small interfering RNA-mediated knockdown of the angiotensin-(1-7) receptor, Mas, increases cell proliferation. Whether alterations in canonical transient receptor potential channels (TRPC) expression contribute to this effect is not clear. In the present study, a basic description of TRPC subtype expression in osteosarcoma cell lines was provided. Read More

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Protective effects of dapagliflozin against oxidative stress-induced cell injury in human proximal tubular cells.

PLoS One 2021 19;16(2):e0247234. Epub 2021 Feb 19.

Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, University of Hull, Hull, United Kingdom.

Elevated reactive oxygen species (ROS) in type 2 diabetes cause cellular damage in many organs. Recently, the new class of glucose-lowering agents, SGLT-2 inhibitors, have been shown to reduce the risk of developing diabetic complications; however, the mechanisms of such beneficial effect are largely unknown. Here we aimed to investigate the effects of dapagliflozin on cell proliferation and cell death under oxidative stress conditions and explore its underlying mechanisms. Read More

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February 2021

TRPC4 ion channel regulations by small-molecular inhibitors and calmodulin.

Cell Calcium 2021 May 29;95:102361. Epub 2021 Jan 29.

Harvard Cryo-EM Center for Structural Biology, Department of Biological Chemistry and Molecular Pharmacology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, 02115, USA. Electronic address:

TRPC4 ion channel was reported to be regulated by small molecular inhibitors and calmodulin. We discuss these findings in the context of other members of TRPC subfamily modulated by different stimulants. Read More

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Contribution of TRPC Channels in Neuronal Excitotoxicity Associated With Neurodegenerative Disease and Ischemic Stroke.

Front Cell Dev Biol 2020 8;8:618663. Epub 2021 Jan 8.

Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States.

The seven canonical members of transient receptor potential (TRPC) proteins form cation channels that evoke membrane depolarization and intracellular calcium concentration ([Ca] ) rise, which are not only important for regulating cell function but their deregulation can also lead to cell damage. Recent studies have implicated complex roles of TRPC channels in neurodegenerative diseases including ischemic stroke. Brain ischemia reduces oxygen and glucose supply to neurons, i. Read More

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January 2021

Suppression of mI in Mouse Small Intestinal Myocytes by General Anaesthetic Ketamine and its Recovery by TRPC4 Agonist (-)-englerin A.

Front Pharmacol 2020 18;11:594882. Epub 2020 Dec 18.

ESC "Institute of Biology and Medicine", Taras Shevchenko National University of Kyiv, Kyiv, Ukraine.

A better understanding of the negative impact of general anesthetics on gastrointestinal motility requires thorough knowledge of their molecular targets. In this respect the muscarinic cationic current (mI carried mainly via TRPC4 channels) that initiates cholinergic excitation-contraction coupling in the gut is of special interest. Here we aimed to characterize the effects of one of the most commonly used "dissociative anesthetics", ketamine, on mI. Read More

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December 2020

Calmodulin binds to Drosophila TRP with an unexpected mode.

Structure 2021 Apr 15;29(4):330-344.e4. Epub 2020 Dec 15.

Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China; Greater Bay Biomedical Innocenter, Shenzhen Bay Laboratory, Shenzhen 518055, China; Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address:

Drosophila TRP is a calcium-permeable cation channel essential for fly visual signal transduction. During phototransduction, Ca mediates both positive and negative feedback regulation on TRP channel activity, possibly via binding to calmodulin (CaM). However, the molecular mechanism underlying Ca modulated CaM/TRP interaction is poorly understood. Read More

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Structural basis of TRPC4 regulation by calmodulin and pharmacological agents.

Elife 2020 11 25;9. Epub 2020 Nov 25.

Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.

Canonical transient receptor potential channels (TRPC) are involved in receptor-operated and/or store-operated Ca signaling. Inhibition of TRPCs by small molecules was shown to be promising in treating renal diseases. In cells, the channels are regulated by calmodulin (CaM). Read More

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November 2020

Stim-activated TRPC-ORAI channels in pulmonary hypertension induced by chronic intermittent hypoxia.

Pulm Circ 2020 Jul-Sep;10(1 Suppl):13-22. Epub 2020 Oct 13.

Laboratorio de Neurobiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.

Obstructive sleep apnea (OSA), a breathing disorder featured by chronic intermittent hypoxia (CIH) is associated with pulmonary hypertension (PH). Rodents exposed to CIH develop pulmonary vascular remodeling and PH, but the pathogenic mechanisms are not well known. Overexpression of Stim-activated Transient Receptor Potential Channels (TRPC) and Calcium Release-Activated Calcium Channel Protein (ORAI) TRPC-ORAI Ca channels (STOC) has been involved in pulmonary vascular remodeling and PH in sustained hypoxia. Read More

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October 2020

Preventive treatment with ginsenoside Rb1 ameliorates monocrotaline-induced pulmonary arterial hypertension in rats and involves store-operated calcium entry inhibition.

Pharm Biol 2020 Dec;58(1):1055-1063

The Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, People's Republic of China.

Context: Ginsenoside Rb1, the main active ingredient of ginseng, exhibits depression of store-operated calcium entry (SOCE) and related vasoconstriction in pulmonary arteries derived from pulmonary hypertension (PH) rats. However, the effects of ginsenoside Rb1 on PH remain unclear.

Objective: This study explored the possibility of using ginsenoside Rb1 as an preventive medication for type I PH, i. Read More

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December 2020

[Correlation between transient receptor potential canonical channel with heart and kidney injure of rat model of obstructive sleep apnea hypopnea syndrome].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2020 Aug;49(4):439-446

Department of Hypertension, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.

Objective: To investigate the expression of transient receptor potential canonical channels (TRPCs) in the heart and kidney of rat model of obstructive sleep apnea hypopnea syndrome (OSAHS).

Methods: Eighteen male SD rats were randomly assigned to intermittent hypoxia (IH) group (=9 ) and control group (=9). In IH group, rats were placed in a chamber and exposed to intermittent hypoxia for 8h (10AM-6PM) daily. Read More

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Bridgehead Modifications of Englerin A Reduce TRPC4 Activity and Intravenous Toxicity but not Cell Growth Inhibition.

ACS Med Chem Lett 2020 Sep 3;11(9):1711-1716. Epub 2020 Aug 3.

Molecular Targets Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, United States.

Modifications at the bridgehead position of englerin A were made to explore the effects of variation at this site on the molecule for biological activity, as judged by the NCI 60 screen, in which englerin A is highly potent and selective for renal cancer cells. Replacement of the isopropyl group by other, larger substituents yielded compounds which displayed excellent selectivity and potency comparable to the natural product. Selected compounds were also evaluated for their effect on the ion channel TRPC4 as well as for intravenous toxicity in mice, and these had lower potency in both assays compared to englerin A. Read More

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September 2020

Carboxyl terminus of Hsc70-interacting protein (CHIP) promotes pulmonary artery smooth muscle cell (PASMC) proliferation enhancement of intracellular Ca concentration ([Ca]).

Authors:
Fang Dong Jun Zhang

Exp Lung Res 2020 11 2;46(9):332-340. Epub 2020 Sep 2.

College of Medicine and Health, Lishui University, Lishui, PR China.

Aims Of The Study: To investigate the effect of carboxyl terminus of Hsc70-interacting protein (CHIP) on pulmonary arterial smooth muscle cell (PASMC) proliferation and the underlying mechanism. PASMCs were harvested from distal PAs isolated from SD rat lungs and cultured. After CHIP overexpression, PASMCs were exposed to normoxia or hypoxia for 60 h. Read More

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November 2020

Transient Receptor Potential Canonical (TRPC) Channels: Then and Now.

Cells 2020 08 28;9(9). Epub 2020 Aug 28.

The Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Twenty-five years ago, the first mammalian Transient Receptor Potential Canonical (TRPC) channel was cloned, opening the vast horizon of the TRPC field. Today, we know that there are seven TRPC channels (TRPC1-7). TRPCs exhibit the highest protein sequence similarity to the TRP channels. Read More

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TRPC4 as a coincident detector of G and G signaling: mechanisms and pathophysiological implications.

Curr Opin Physiol 2020 Oct 2;17:34-41. Epub 2020 Jul 2.

Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.

TRPC channels are Ca-permeable nonselective cation channels activated downstream from phospholipase C (PLC). Although most TRPC channels can be activated by stimulating G-coupled receptors, TRPC4 requires simultaneous stimulation of G-coupled receptors, making it a perfect detector of coincident G and G signaling. Evidence shows that activated Gα proteins work together with PLCδ1 to induce robust TRPC4 activation and the process is accelerated by stimulation of other PLC isozymes, such as PLCβ through G proteins. Read More

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October 2020

Epigallocatechin-3-gallate mobilizes intracellular Ca in prostate cancer cells through combined Ca entry and Ca-induced Ca release.

Life Sci 2020 Oct 8;258:118232. Epub 2020 Aug 8.

Istituto di Biofisica, Consiglio Nazionale delle Ricerche, via De Marini 6, 16149 Genova, Italy; Dipartimento di Farmacia, Università di Genova, Viale Benedetto XV, 3 16132 Genova, Italy.

Aims: To elucidate the mechanism by which (-)-epigallocatechin-3-gallate (EGCG) mediates intracellular Ca increase in androgen-independent prostate cancer (PCa) cells.

Main Methods: Following exposure to different doses of EGCG, viability of DU145 and PC3 PCa cells was evaluated by MTT assay and the intracellular Ca dynamics by the fluorescent Ca chelator Fura-2. The expression of different channels was investigated by qPCR analysis and sulfhydryl bonds by Ellman's assay. Read More

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October 2020

Transcriptional signatures regulated by TRPC1/C4-mediated Background Ca entry after pressure-overload induced cardiac remodelling.

Prog Biophys Mol Biol 2021 Jan 29;159:86-104. Epub 2020 Jul 29.

Pharmakologisches Institut, Ruprecht-Karls-Universität Heidelberg, 69120, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Heidelberg, 69120, Germany. Electronic address:

Aims: After summarizing current concepts for the role of TRPC cation channels in cardiac cells and in processes triggered by mechanical stimuli arising e.g. during pressure overload, we analysed the role of TRPC1 and TRPC4 for background Ca entry (BGCE) and for cardiac pressure overload induced transcriptional remodelling. Read More

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January 2021

The Expression of Cold-Inducible RNA-Binding Protein mRNA in Sow Genital Tract Is Modulated by Natural Mating, But Not by Seminal Plasma.

Int J Mol Sci 2020 Jul 27;21(15). Epub 2020 Jul 27.

Department of Biomedical and Clinical Sciences (BKV), Division of Children's and Women Health (BKH), Obstetrics and Gynaecology, Linköping University, 58185 Linköping, Sweden.

The RNA-binding proteins (RBPs), some of them induced by transient receptor potential (TRP) ion channels, are crucial regulators of RNA function that can contribute to reproductive pathogenesis, including inflammation and immune dysfunction. This study aimed to reveal the influence of spermatozoa, seminal plasma, or natural mating on mRNA expression of RBPs and TRP ion channels in different segments of the internal genital tract of oestrous, preovulatory sows. Particularly, we focused on mRNA expression changes of the cold-inducible proteins (CIPs) and related TRP channels. Read More

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Transient receptor potential canonical 5 channel is involved in the cardiac damage related to obstructive sleep apnea-hypopnea syndrome in rats.

Ann Palliat Med 2020 May 12;9(3):895-902. Epub 2020 May 12.

Department of Hypertension, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.

Background: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is recognized as an independent risk factor of cardiovascular disease. The release of Ca2+ mediated by transient receptor potential canonical (TRPC) channels participates in the hypoxia-induced pathophysiological changes in the cardiovascular systems in case of OSAHS. This study aimed to investigate which subtypes of TRPCs were involved in OSAHS in a rat model of intermittent hypoxia. Read More

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Chromogranin A (CGA)-derived polypeptide (CGA) inhibits TNF-α-induced vascular endothelial hyper-permeability through SOC-related Ca signaling.

Peptides 2020 09 5;131:170297. Epub 2020 May 5.

Department of Emergency, The Third People's Hospital of Chengdu, The Second Affiliated Chengdu Clinical College of Chongqing Medical University, Chengdu, Sichuan 610031, PR China.

CGA (Vasostatin-1, VS-1) a N-terminal Chromogranin A (CGA)-derived peptide, has been shown to have a protective effect against TNF-α-induced impairment of endothelial cell integrity. However, the mechanisms of this effect have not yet been clarified. CGA (Chromofungin, CHR) is an important bioactive fragment of CGA. Read More

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September 2020

Intracellular acidification facilitates receptor-operated TRPC4 activation through PLCδ1 in a Ca -dependent manner.

J Physiol 2020 07 22;598(13):2651-2667. Epub 2020 May 22.

Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.

Key Points: Receptor-operated activation of TRPC4 cation channels requires G proteins and phospholipase-Cδ1 (PLCδ1) activation by intracellular Ca . Concurrent stimulation of the G pathway accelerates G activation of TRPC4, which is not mimicked by increasing cytosolic Ca . The kinetic effect of G was diminished by alkaline intracellular pH (pH ) and increased pH buffer capacity. Read More

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Transient Receptor Potential Canonical 4 and 5 Channel Antagonist ML204 Depolarized Pacemaker Potentials of Interstitial Cells of Cajal.

J Neurogastroenterol Motil 2020 09;26(4):521-528

Department of Physiology, College of Medicine, Chosun University, Gwangju, Korea.

Background/aims: To investigate an effect of ML204 (an inhibitor of transient receptor potential canonical 4 and 5 [TRPC4/5] channels) on interstitial cells of Cajal (ICCs) and therefore determine whether TRPC4/5 channels act on ICC-generated pacemaker activity.

Methods: We enforced whole cell patch clamp analysis, measurements of the intracellular Ca concentration, and reverse transcription polymerase chain reaction to determine the effect of ML204 (10 μM) or englerin A (a selective activator of TRPC4/5 channeles, 10 μM) and the existence of TRPC4/5 in mouse small intestinal ICC.

Results: Treatment of ICCs with ML204 or englerin A caused the membrane potentials to depolarize. Read More

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September 2020

Sensory Neuron-Expressed TRPC4 Is a Target for the Relief of Psoriasiform Itch and Skin Inflammation in Mice.

J Invest Dermatol 2020 11 11;140(11):2221-2229.e6. Epub 2020 Apr 11.

Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, Ohio, USA. Electronic address:

Psoriasis is an inflammatory skin disease associated with itch, which is a troublesome symptom with a few therapeutic options. TRPC4 is highly expressed in dorsal root ganglia (DRGs). Recently, we have revealed itch signaling in DRG neurons by which TRPC4 mediates itch to serotonergic antidepressants and demonstrated the antipruritic effect of the TRPC4 inhibitor ML204. Read More

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November 2020

Tannic acid, a vasodilator present in wines and beverages, stimulates Ca influx via TRP channels in bEND.3 endothelial cells.

Biochem Biophys Res Commun 2020 05 17;526(1):117-121. Epub 2020 Mar 17.

Department of Physiology, China Medical University, Taichung, Taiwan. Electronic address:

Tannic acid (TA) is a polyphenol compound present in wines and many beverages. Although previous works have shown that TA could cause vasodilation in an endothelial cell (EC)-dependent manner, there is hitherto no report showing whether TA could raise EC cytosolic Ca concentration. In this work we examined the effects of TA on cytosolic Ca of mouse brain bEND. Read More

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Chrysin Alleviates Monocrotaline-Induced Pulmonary Hypertension in Rats Through Regulation of Intracellular Calcium Homeostasis in Pulmonary Arterial Smooth Muscle Cells.

J Cardiovasc Pharmacol 2020 06;75(6):596-602

College of Medicine and Health, Lishui University, Lishui, Zhejiang, China; and.

Chrysin (CH) is the main ingredient of many medicinal plants. Our previous study showed that CH could suppress hypoxia-induced pulmonary arterial smooth muscle cells proliferation and alleviate chronic hypoxia-induced pulmonary hypertension by targeting store-operated Ca entry (SOCE)-[Ca]i pathway. In this study, we investigated the effect of CH on monocrotaline-induced pulmonary hypertension (MCTPH) and the mechanism behind it. Read More

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Shape Similarity by Fractal Dimensionality: An Application in the de novo Design of (-)-Englerin A Mimetics.

ChemMedChem 2020 04 12;15(7):566-570. Epub 2020 Mar 12.

Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.

Molecular shape and pharmacological function are interconnected. To capture shape, the fractal dimensionality concept was employed, providing a natural similarity measure for the virtual screening of de novo generated small molecules mimicking the structurally complex natural product (-)-englerin A. Two of the top-ranking designs were synthesized and tested for their ability to modulate transient receptor potential (TRP) cation channels which are cellular targets of (-)-englerin A. Read More

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Blood multiomics reveal insights into population clusters with low prevalence of diabetes, dyslipidemia and hypertension.

PLoS One 2020 5;15(3):e0229922. Epub 2020 Mar 5.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

Diabetes, dyslipidemia and hypertension are important metabolic diseases that impose a great burden on many populations worldwide. However, certain population strata have reduced prevalence for all three diseases, but the underlying mechanisms are poorly understood. We sought to identify the phenotypic, genomic and metabolomic characteristics of the low-prevalence population to gain insights into possible innate non-susceptibility against metabolic diseases. Read More

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TRPC1 Regulates the Activity of a Voltage-Dependent Nonselective Cation Current in Hippocampal CA1 Neurons.

Cells 2020 02 18;9(2). Epub 2020 Feb 18.

Pharmakologisches Institut, BPC-Marburg, Fachbereich Medizin, Philipps-Universität Marburg, Karl-von-Frisch-Straße 2, 35043 Marburg, Germany.

The cation channel subunit TRPC1 is strongly expressed in central neurons including neurons in the CA1 region of the hippocampus where it forms complexes with TRPC4 and TRPC5. To investigate the functional role of TRPC1 in these neurons and in channel function, we compared current responses to group I metabotropic glutamate receptor (mGluR I) activation and looked for major differences in dendritic morphology in neurons from and mice. mGluR I stimulation resulted in the activation of a voltage-dependent nonselective cation current in both genotypes. Read More

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February 2020

Endothelial Transient Receptor Potential Channels and Vascular Remodeling: Extracellular Ca Entry for Angiogenesis, Arteriogenesis and Vasculogenesis.

Front Physiol 2019 21;10:1618. Epub 2020 Jan 21.

Laboratory of General Physiology, Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, Pavia, Italy.

Vasculogenesis, angiogenesis and arteriogenesis represent three crucial mechanisms involved in the formation and maintenance of the vascular network in embryonal and post-natal life. It has long been known that endothelial Ca signals are key players in vascular remodeling; indeed, multiple pro-angiogenic factors, including vascular endothelial growth factor, regulate endothelial cell fate through an increase in intracellular Ca concentration. Transient Receptor Potential (TRP) channel consist in a superfamily of non-selective cation channels that are widely expressed within vascular endothelial cells. Read More

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January 2020