The role of transient receptor potential vanilloid 2 channel in cardiac aging

Jones, Shannon; Mann, Adrien; Worley, Mariah; Fulford, Logan; Hall, David; Karani, Rajiv; Jiang, Min; Robbins, Nathan; Rubinstein, Jack; Koch, Sheryl E.

doi:10.1007/s40520-016-0663-x

Cited by 12 publications

(9 citation statements)

References 27 publications

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“…A knockout of TRPV2 protects hearts against pressure-overload-induced hypertrophy, but produces no protection against AngII or β-adrenergic activation-induced hypertrophy, indicating that TRPV2 regulates cardiac hypertrophy through stretch activation [179]. A knockout of TRPV2 in mice also reduces age-related fibrosis and hypertrophy [210]. Application of the TRPV2 blocker Tranilast blunts the hypertrophic and fibrotic response to pressure-overload-induced hypertrophy within four weeks [180].…”

Section: Trpv2 and Cardiac Fibrosismentioning

confidence: 99%

Ca2+ Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases

Feng

Armillei

et al. 2019

JCDD

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Cardiac fibrosis is the excessive deposition of extracellular matrix proteins by cardiac fibroblasts and myofibroblasts, and is a hallmark feature of most heart diseases, including arrhythmia, hypertrophy, and heart failure. This maladaptive process occurs in response to a variety of stimuli, including myocardial injury, inflammation, and mechanical overload. There are multiple signaling pathways and various cell types that influence the fibrogenesis cascade. Fibroblasts and myofibroblasts are central effectors. Although it is clear that Ca2+ signaling plays a vital role in this pathological process, what contributes to Ca2+ signaling in fibroblasts and myofibroblasts is still not wholly understood, chiefly because of the large and diverse number of receptors, transporters, and ion channels that influence intracellular Ca2+ signaling. Intracellular Ca2+ signals are generated by Ca2+ release from intracellular Ca2+ stores and by Ca2+ entry through a multitude of Ca2+-permeable ion channels in the plasma membrane. Over the past decade, the transient receptor potential (TRP) channels have emerged as one of the most important families of ion channels mediating Ca2+ signaling in cardiac fibroblasts. TRP channels are a superfamily of non-voltage-gated, Ca2+-permeable non-selective cation channels. Their ability to respond to various stimulating cues makes TRP channels effective sensors of the many different pathophysiological events that stimulate cardiac fibrogenesis. This review focuses on the mechanisms of Ca2+ signaling in fibroblast differentiation and fibrosis-associated heart diseases and will highlight recent advances in the understanding of the roles that TRP and other Ca2+-permeable channels play in cardiac fibrosis.

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Section: Trpv2 and Cardiac Fibrosismentioning

confidence: 99%

Ca2+ Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases

Feng

Armillei

et al. 2019

JCDD

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“…Other reports suggested that TRPV2, TRPV3, and TRPV4 channels also participate in cardiac fibrosis. TRPV2 functional deletion was associated with a decreased development of fibrosis associated with aging (Jones et al., 2017), while TRPV2 upregulation was associated with enlarged hearts, increased fibrosis, and myocardial structural defects in patients with dilated cardiomyopathy (Iwata et al, 2013). Furthermore, TRPV3 activation intensified cardiac fibrosis, stimulating cardiac fibroblast proliferation in the pressure-overloaded rat hearts (Liu et al., 2018).…”

Section: Role Of Trp Channels In the Adverse Cardiac Remodelingmentioning

confidence: 99%

TRP Channels: Current Perspectives in the Adverse Cardiac Remodeling

et al. 2019

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Calcium is an important second messenger required not only for the excitation-contraction coupling of the heart but also critical for the activation of cell signaling pathways involved in the adverse cardiac remodeling and consequently for the heart failure. Sustained neurohumoral activation, pressure-overload, or myocardial injury can cause pathologic hypertrophic growth of the heart followed by interstitial fibrosis. The consequent heart’s structural and molecular adaptation might elevate the risk of developing heart failure and malignant arrhythmia. Compelling evidences have demonstrated that Ca 2+ entry through TRP channels might play pivotal roles in cardiac function and pathology. TRP proteins are classified into six subfamilies: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPML (mucolipin), and TRPP (polycystin), which are activated by numerous physical and/or chemical stimuli. TRP channels participate to the handling of the intracellular Ca 2+ concentration in cardiac myocytes and are mediators of different cardiovascular alterations. This review provides an overview of the current knowledge of TRP proteins implication in the pathologic process of some frequent cardiac diseases associated with the adverse cardiac remodeling such as cardiac hypertrophy, fibrosis, and conduction alteration.

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“…Speckle tracking based displacement and strain values were calculated from the SAX view for each individual wall segment using VevoStrain software (Vevo 2100, Version 1.1.1 B1455, VisualSonics) as previously described [31]. Briefly, a single blinded reader loaded the B-mode cine loop into VevoStrain software and ECG measurements taken synchronously with the B-mode cine loop were used to select three to four cardiac cycles out of the cine loop.…”

Section: Speckle Tracking Measurementsmentioning

confidence: 99%

“…The paraffin-embedded blocks were cut into 6μm sections and mounted on slides. Longitudinal heart sections were stained with Masson's Trichrome and images from the left ventricle were analyzed using the Image J software as previously described [31]. The average fibrotic area for each group was determined and each group was analyzed using student t-test.…”

Section: Connective Tissue Analysismentioning

confidence: 99%

Probenecid treatment improves outcomes in a novel mouse model of peripartum cardiomyopathy

et al. 2020

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Probenecid has been used for decades in the treatment of gout but recently has also been found to improve outcomes in patients with heart failure via stimulation of the transient receptor potential vanilloid 2 (TRPV2) channel in cardiomyocytes. This study tested the use of probenecid on a novel mouse model of peripartum cardiomyopathy (PPCM) as a potential treatment option. A human mutation of the human heat shock protein 20 (Hsp20-S10F) in mice has been recently shown to result in cardiomyopathy, when exposed to pregnancies. Treatment with either probenecid or control sucrose water was initiated after the first pregnancy in both wild type and Hsp20-S10F mice. Serial echocardiography was performed during subsequent pregnancies and hearts were collected after the third pregnancies for staining and molecular analysis. Hsp20-S10F mice treated with probenecid had decreased mortality, hypertrophy, TRPV2 expression and molecular parameters of heart failure. Probenecid treatment also decreased apoptosis as evidenced by an increase in the level of Bcl-2/Bax. Probenecid improved survival in a novel mouse model of PPCM and may be an appropriate therapy for humans with PPCM as it has a proven safety and tolerability in patients with heart failure.

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The role of transient receptor potential vanilloid 2 channel in cardiac aging

Abstract: TRPV2 functional deletion is compatible with aging and associated with a decreased development of myocyte hypertrophy and fibrosis. It may be an important target for prevention of age-induced cardiac remodeling.

Cited by 12 publications

References 27 publications

Ca2+ Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases

Ca2+ Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases

TRP Channels: Current Perspectives in the Adverse Cardiac Remodeling

Probenecid treatment improves outcomes in a novel mouse model of peripartum cardiomyopathy

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