TRP Channels in Cardiovascular and Inflammatory Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (15 October 2024) | Viewed by 5938

Special Issue Editors


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Guest Editor
School of Cardiovascular & Metabolic Medicine and Sciences, King's College, London, UK
Interests: sensory nerves; vascular inflammation; TRP receptors; CGRP
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Guest Editor
1. Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Sao Paulo, Brazil
2. School of Cardiovascular Medicine and Sciences, King's College London, London, UK
Interests: inflammation and pain

Special Issue Information

Dear Colleagues,

The transient receptor potential (TRP) family of receptor channels are an exceptional family of receptors that respond to a wide range of cellular and environmental stimuli to influence many biological responses.

In mammals, the TRP channels fit into 28 different proteins, which can be divided into seven subfamilies based on amino acid sequence homology (TRPA–Ankyrin, TRPC–Canonical, TRPM–Melastatin, TRPML–Mucolipin, TRPN–NO-mechano-potential, NOMP, TRPP–Polycystin, TRPV–Vanilloid), of which some have been proposed as sensing a variety of stimuli, including pressure, shear stress, mechanical stretch, oxidative stress, lipid environment alterations, hypertrophic signals, or inflammation products.

The TRP family was first discovered in 1969, followed by the first characterization and cloning of the nociceptive TRP channel (vanilloid receptor TRPV1) in mammalian neurons in 1997. Since then, much knowledge of the various families of TRP ion channels has emerged over the last 25 years; related to their role as a transducer of nociceptive signals and a regulator of cardiovascular functions, as well as in inflammatory disease.

Mechanistically, TRP activation has been associated with the regulation of calcium homeostasis, oxidative stress, and apoptosis, which can be translated to humans and related species in terms of mediating components of a range of cardiovascular and inflammatory conditions, especially those involving the sensation of pain (of which TRPV1 and TRPA1 are primarily involved) or thermal sensations (of which TRPV1, TRPA1 and TRPM8 are primarily involved) and in sensing metabolic influences, to which all channels are capable of contributing. Mechanistically, much still remains to be determined, with research into some areas and diseases still at an early stage. With this in mind, this Special Issue has been designed to bring cutting-edge research to the table for side-by-side comparisons.

The ultimate objective is that the mechanistic studies will lead to new drugs to treat TRP-mediated conditions. Whilst some historic vegetable-derived compounds that influence the TRP channels have been used therapeutically for many years (the chilli extract capsaicin, a TRPV1 agonist that depletes sensory nerves leading to analgesia, is best known), others, such as the development of feasible TRP antagonists for use as selective therapeutics with minimal side effects, have been elusive to date. Whilst some effective antagonists have been created (e.g., for the TRPV1 receptor), others (e.g., the TRPA1 receptor) have been associated with less efficacious effects. Additionally, the breadth of activation mechanisms has led to troublesome side effects with some antagonists  (e.g., TRPV1) that have been difficult to limit.

This Special Issue enables us to invite manuscripts associated with TRP channels, to build on knowledge of biological functions of TRP and novel potential therapeutic interventions (drug discovery) for cardiovascular and inflammatory diseases. This can be either via a review or original research.  Areas of interest include, but are not limited to:

  • Design of novel TRP ligands and evidence of functional relevance;
  • Role of TRP channels in biological functions;
  • Mechanistic studies on TRP channels;
  • Role of TRP channels in cardiovascular disease and inflammation;
  • Development and testing of novel therapeutic agents.

Prof. Dr. Susan D. Brain
Dr. Soraia Katia Pereira Costa
Guest Editors

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Published Papers (3 papers)

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Research

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23 pages, 5538 KiB  
Article
TRPA1 Covalent Ligand JT010 Modifies T Lymphocyte Activation
by Katalin Szabó, Géza Makkai, János Konkoly, Viktória Kormos, Balázs Gaszner, Tímea Berki and Erika Pintér
Biomolecules 2024, 14(6), 632; https://doi.org/10.3390/biom14060632 - 28 May 2024
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Abstract
Transient Receptor Potential Ankyrin 1 (TRPA1) is a non-selective cation channel involved in sensitivity to a plethora of irritating agents and endogenous mediators of oxidative stress. TRPA1 influences neuroinflammation and macrophage and lymphocyte functions, but its role is controversial in immune cells. We [...] Read more.
Transient Receptor Potential Ankyrin 1 (TRPA1) is a non-selective cation channel involved in sensitivity to a plethora of irritating agents and endogenous mediators of oxidative stress. TRPA1 influences neuroinflammation and macrophage and lymphocyte functions, but its role is controversial in immune cells. We reported earlier a detectable, but orders-of-magnitude-lower level of Trpa1 mRNA in monocytes and lymphocytes than in sensory neurons by qRT-PCR analyses of cells from lymphoid organs of mice. Our present goals were to (a) further elucidate the expression of Trpa1 mRNA in immune cells by RNAscope in situ hybridization (ISH) and (b) test the role of TRPA1 in lymphocyte activation. RNAscope ISH confirmed that Trpa1 transcripts were detectable in CD14+ and CD4+ cells from the peritoneal cavity of mice. A selective TRPA1 agonist JT010 elevated Ca2+ levels in these cells only at high concentrations. However, a concentration-dependent inhibitory effect of JT010 was observed on T-cell receptor (TcR)-induced Ca2+ signals in CD4+ T lymphocytes, while JT010 neither modified B cell activation nor ionomycin-stimulated Ca2+ level. Based on our present and past findings, TRPA1 activation negatively modulates T lymphocyte activation, but it does not appear to be a key regulator of TcR-stimulated calcium signaling. Full article
(This article belongs to the Special Issue TRP Channels in Cardiovascular and Inflammatory Disease)
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17 pages, 4125 KiB  
Article
Transient Receptor Potential Canonical 5 (TRPC5): Regulation of Heart Rate and Protection against Pathological Cardiac Hypertrophy
by Pratish Thakore, James E. Clark, Aisah A. Aubdool, Dibesh Thapa, Anna Starr, Paul A. Fraser, Keith Farrell-Dillon, Elizabeth S. Fernandes, Ian McFadzean and Susan D. Brain
Biomolecules 2024, 14(4), 442; https://doi.org/10.3390/biom14040442 - 4 Apr 2024
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Abstract
TRPC5 is a non-selective cation channel that is expressed in cardiomyocytes, but there is a lack of knowledge of its (patho)physiological role in vivo. Here, we examine the role of TRPC5 on cardiac function under basal conditions and during cardiac hypertrophy. Cardiovascular parameters [...] Read more.
TRPC5 is a non-selective cation channel that is expressed in cardiomyocytes, but there is a lack of knowledge of its (patho)physiological role in vivo. Here, we examine the role of TRPC5 on cardiac function under basal conditions and during cardiac hypertrophy. Cardiovascular parameters were assessed in wild-type (WT) and global TRPC5 knockout (KO) mice. Despite no difference in blood pressure or activity, heart rate was significantly reduced in TRPC5 KO mice. Echocardiography imaging revealed an increase in stroke volume, but cardiac contractility was unaffected. The reduced heart rate persisted in isolated TRPC5 KO hearts, suggesting changes in basal cardiac pacing. Heart rate was further investigated by evaluating the reflex change following drug-induced pressure changes. The reflex bradycardic response following phenylephrine was greater in TRPC5 KO mice but the tachycardic response to SNP was unchanged, indicating an enhancement in the parasympathetic control of the heart rate. Moreover, the reduction in heart rate to carbachol was greater in isolated TRPC5 KO hearts. To evaluate the role of TRPC5 in cardiac pathology, mice were subjected to abdominal aortic banding (AAB). An exaggerated cardiac hypertrophy response to AAB was observed in TRPC5 KO mice, with an increased expression of hypertrophy markers, fibrosis, reactive oxygen species, and angiogenesis. This study provides novel evidence for a direct effect of TRPC5 on cardiac function. We propose that (1) TRPC5 is required for maintaining heart rate by regulating basal cardiac pacing and in response to pressure lowering, and (2) TRPC5 protects against pathological cardiac hypertrophy. Full article
(This article belongs to the Special Issue TRP Channels in Cardiovascular and Inflammatory Disease)
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Review

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25 pages, 1832 KiB  
Review
TRPV Channels in Osteoarthritis: A Comprehensive Review
by Changshun Chen, Fei Yang, Rongjin Chen, Chenhui Yang, Hefang Xiao, Bin Geng and Yayi Xia
Biomolecules 2024, 14(3), 292; https://doi.org/10.3390/biom14030292 - 29 Feb 2024
Cited by 4 | Viewed by 2529
Abstract
Osteoarthritis (OA) is a debilitating joint disorder that affects millions of people worldwide. Despite its prevalence, our understanding of the underlying mechanisms remains incomplete. In recent years, transient receptor potential vanilloid (TRPV) channels have emerged as key players in OA pathogenesis. This review [...] Read more.
Osteoarthritis (OA) is a debilitating joint disorder that affects millions of people worldwide. Despite its prevalence, our understanding of the underlying mechanisms remains incomplete. In recent years, transient receptor potential vanilloid (TRPV) channels have emerged as key players in OA pathogenesis. This review provides an in-depth exploration of the role of the TRPV pathway in OA, encompassing its involvement in pain perception, inflammation, and mechanotransduction. Furthermore, we discuss the latest research findings, potential therapeutic strategies, and future directions in the field, shedding light on the multifaceted nature of TRPV channels in OA. Full article
(This article belongs to the Special Issue TRP Channels in Cardiovascular and Inflammatory Disease)
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