Transient receptor potential channel M2 contributes to neointimal hyperplasia in vascular walls

Ru, Xiaochen; Zheng, Chang‐Bo; Zhao, Qiannan; Lan, Hui‐Yao; Huang, Yü; Wan, Song; Mori, Yasuo; Yao, Xiaoqiang

doi:10.1016/j.bbadis.2015.03.014

Cited by 11 publications

(8 citation statements)

References 44 publications

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“…For example, L-type Ca 2+ channels are downregulated and transient receptor potential cation (TRPC) channels are upregulated in VSMCs [156]. Of the TRPCs, the Ca 2+ -permeable TRPM2 channel was suggested to be a sensor of oxidative stress [158], and its activation by ROS leads to intracellular Ca 2+ overload inflammation [159], VSMC, migration, proliferation and apoptosis [158, 160, 161]. Another TRPC isoform, TRPC1, has also been implicated in neointimal proliferation [162].…”

Section: Recent Advancesmentioning

confidence: 99%

Mouse models of atherosclerosis: a historical perspective and recent advances

et al. 2017

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Atherosclerosis represents a significant cause of morbidity and mortality in both the developed and developing countries. Animal models of atherosclerosis have served as valuable tools for providing insights on its aetiology, pathophysiology and complications. They can be used for invasive interrogation of physiological function and provide a platform for testing the efficacy and safety of different pharmacological therapies. Compared to studies using human subjects, animal models have the advantages of being easier to manage, with controllable diet and environmental risk factors. Moreover, pathophysiological changes can be induced either genetically or pharmacologically to study the harmful effects of these interventions. There is no single ideal animal model, as different systems are suitable for different research objectives. A good understanding of the similarities and differences to humans enables effective extrapolation of data for translational application. In this article, we will examine the different mouse models for the study and elucidation of the pathophysiological mechanisms underlying atherosclerosis. We also review recent advances in the field, such as the role of oxidative stress in promoting endoplasmic reticulum stress, mitochondrial dysfunction and mitochondrial DNA damage, which can result in vascular inflammation and atherosclerosis. Finally, novel therapeutic approaches to reduce vascular damage caused by chronic inflammation using microRNA and nano-medicine technology, are discussed.

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Section: Recent Advancesmentioning

confidence: 99%

Mouse models of atherosclerosis: a historical perspective and recent advances

et al. 2017

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“…These vaccine peptides can successfully attenuate atherosclerosis in mouse model 6,7 . TRPM2 is expressed in macrophages and vascular cells in vascular walls 10,11,13, 17 . Recent studies from us and others showed that TRPM2 has proinflammatory role in vascular walls, consequently promoting atherosclerotic progression 14, 15 .…”

Section: Discussionmentioning

confidence: 99%

“…The E3 domain is a region that is hydrophilic, C-terminal to the fifth transmembrane domain (S5) and close to the predicted ion pore 16 . We have previously immunized rabbits with E3 region-based rat TRPM2 short peptide to generate a polyclonal anti-TRPM2 antibody 11, 17 . The generated antibody TM2E3 can effectively inhibit the activity of human and rat TRPM2 channels in patch clamp recording and Ca 2+ measurement study 11 .…”

Section: Introductionmentioning

confidence: 99%

“…The generated antibody TM2E3 can effectively inhibit the activity of human and rat TRPM2 channels in patch clamp recording and Ca 2+ measurement study 11 . Intriguingly, TM2E3 also inhibits several cellular processes that are tightly associated with atherosclerotic development, including proliferation and migration of vascular smooth muscle cells and ROS-induced vascular cell death in murine models 17 .…”

Section: Introductionmentioning

confidence: 99%

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Active immunization using TRPM2 peptide vaccine attenuates atherosclerotic progression in a mouse model of atherosclerosis

Yao

Ying

Zhang

et al. 2022

Preprint

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Atherosclerosis is one of the leading causes of cardiovascular diseases and mortality around the world. One exciting strategy for atherosclerosis treatment is immunotherapy, especially active immunization. Active immunization relies on the delivery of antigens in a vaccine platform to introduce humoral and cellular immunity alleviating atherosclerotic progression. TRPM2 is an ROS-activated Ca2+-permeable ion channel that can promote atherosclerosis via stimulating vascular inflammation. In the present study, we developed a strategy of active immunization with TRPM2 E3 domain peptide in a vaccine platform, aiming to induce endogenous production of anti-TRPM2 blocking antibody in mice in vivo, consequently inhibiting TRPM2 channel activity to alleviate atherosclerotic progression. The results show that immunization with a pig TRPM2 E3 region-based peptide (P1) could effectively alleviate high cholesterol diet-induced atherosclerosis in ApoE-/- mice. We worked out the best vaccine formulation for most effective atheroprotection, namely P1 at the dose of 67.5 µg per mouse (2.5 mg/kg body weight) with aluminium salts as adjuvant. The present study laid the foundation for future clinical trials using TRPM2 E3 vaccine for potential therapeutic option against atherosclerosis.

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“…Similar increased expression of TRPC1 was also observed in the intimal layer of human vein graft samples. Thus, these channels may be novel therapeutic targets for occlusive vascular diseases [154,155].…”

Section: Vascular Stenosis After Bypass Surgery and Angioplastymentioning

confidence: 99%

“TRP inflammation” relationship in cardiovascular system

2015

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Despite considerable advances in the research and treatment, the precise relationship between inflammation and cardiovascular (CV) disease remains incompletely understood. Therefore, understanding the immunoinflammatory processes underlying the initiation, progression, and exacerbation of many cardiovascular diseases is of prime importance. The innate immune system has an ancient origin and is well conserved across species. Its activation occurs in response to pathogens or tissue injury. Recent studies suggest that altered ionic balance, and production of noxious gaseous mediators link to immune and inflammatory responses with altered ion channel expression and function. Among plausible candidates for this are transient receptor potential (TRP) channels that function as polymodal sensors and scaffolding proteins involved in many physiological and pathological processes. In this review, we will first focus on the relevance of TRP channel to both exogenous and endogenous factors related to innate immune response and transcription factors related to sustained inflammatory status. The emerging role of inflammasome to regulate innate immunity and its possible connection to TRP channels will also be discussed. Secondly, we will discuss about the linkage of TRP channels to inflammatory CV diseases, from a viewpoint of inflammation in a general sense which is not restricted to the innate immunity. These knowledge may serve to provide new insights into the pathogenesis of various inflammatory CV diseases and their novel therapeutic strategies.

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Transient receptor potential channel M2 contributes to neointimal hyperplasia in vascular walls

Abstract: These data suggest a critical functional role of TRPM2 in the progression of neointimal hyperplasia. The study also highlights the possibility of targeting TRPM2 as a potential therapeutic option for the treatment of occlusive vascular diseases.

Cited by 11 publications

References 44 publications

Mouse models of atherosclerosis: a historical perspective and recent advances

Mouse models of atherosclerosis: a historical perspective and recent advances

Active immunization using TRPM2 peptide vaccine attenuates atherosclerotic progression in a mouse model of atherosclerosis

“TRP inflammation” relationship in cardiovascular system

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