Metabolism regulator adiponectin prevents cardiac remodeling and ventricular arrhythmias via sympathetic modulation in a myocardial infarction model

Zhou, Zhen; Liu, Chengzhe; Xu, Saiting; Wang, Jun; Guo, Feng-Biao; Duan, Shoupeng; Deng, Qiang; Ji, Sun; Yu, Fu; Zhou, Yuyang; Wang, Meng; Wang, Yueyi; Zhou, Liping; Jiang, Hong; Yu, Lilei

doi:10.1007/s00395-022-00939-2

Cited by 28 publications

(20 citation statements)

References 59 publications

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“…Adiponectin levels may decline with chronic stress (283), an effect likely to favour cardiac hypertrophy. Adiponectin was recently shown to limit cardiac sympathetic and myocardial remodelling after infarction in dogs (284). Sex differences in adiponectin responses to stress have yet to be examined in detail.…”

Section: Adipokinesmentioning

confidence: 99%

“…Altered adipokine signalling may also play some role. Adiponectin is cardioprotective, limiting hypertrophy and heart failure (675,676) and protecting against sympathetic and myocardial remodelling after infarction (284). Adiponectin levels are generally repressed with chronic stress (283), potentially facilitating stress-dependent dysfunction and hypertrophy.…”

Section: Stress Modifies Myocardial Control and Promotes Hypertrophy ...mentioning

confidence: 99%

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The sex-dependent response to psychosocial stress and ischaemic heart disease

Helman

Headrick

Stapelberg

et al. 2023

Front. Cardiovasc. Med.

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Stress is an important risk factor for modern chronic diseases, with distinct influences in males and females. The sex specificity of the mammalian stress response contributes to the sex-dependent development and impacts of coronary artery disease (CAD). Compared to men, women appear to have greater susceptibility to chronic forms of psychosocial stress, extending beyond an increased incidence of mood disorders to include a 2- to 4-fold higher risk of stress-dependent myocardial infarction in women, and up to 10-fold higher risk of Takotsubo syndrome—a stress-dependent coronary-myocardial disorder most prevalent in post-menopausal women. Sex differences arise at all levels of the stress response: from initial perception of stress to behavioural, cognitive, and affective responses and longer-term disease outcomes. These fundamental differences involve interactions between chromosomal and gonadal determinants, (mal)adaptive epigenetic modulation across the lifespan (particularly in early life), and the extrinsic influences of socio-cultural, economic, and environmental factors. Pre-clinical investigations of biological mechanisms support distinct early life programming and a heightened corticolimbic-noradrenaline-neuroinflammatory reactivity in females vs. males, among implicated determinants of the chronic stress response. Unravelling the intrinsic molecular, cellular and systems biological basis of these differences, and their interactions with external lifestyle/socio-cultural determinants, can guide preventative and therapeutic strategies to better target coronary heart disease in a tailored sex-specific manner.

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Section: Adipokinesmentioning

confidence: 99%

Section: Stress Modifies Myocardial Control and Promotes Hypertrophy ...mentioning

confidence: 99%

The sex-dependent response to psychosocial stress and ischaemic heart disease

Helman

Headrick

Stapelberg

et al. 2023

Front. Cardiovasc. Med.

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“…39 Previously, we demonstrated that inflammatory cytokines and chemokines in the LSG contributed to myocardial ischemia-induced VAs. 14 Studies have shown that using CNT coatings on implants can reduce inflammatory signals and responses. 40,41 In this study, PC−CNTs exhibited a significant inhibitory effect on LSG neural activity and function, leading to a decrease in the occurrence of VAs.…”

Section: Modulation Of Transcriptional Expression By Pc− Cnts In the Lsgmentioning

confidence: 99%

“…Myocardial ischemia can decrease the HF power (indicating a reduction in parasympathetic activity) and enhance the LF power and LF/HF (indicating increased sympathetic activity). 14 However, treatment with PC−CNTs suppressed the myocardial ischemia-induced changes, indicating that PC−CNTs significantly alleviated myocardial ischemia-induced cardiac sympathetic overactivation (Figure 5A−C). Myocardial ischemia markedly increased the firing of the LSG; however, PC− CNTs significantly inhibited the frequency and amplitude of LSG spikes (Figure 5D,E).…”

Section: Pc−cnts Suppressed Myocardial Ischemia-induced Sympathetic O...mentioning

confidence: 99%

“…Cardiac nerve sprouting and sympathetic hyperinnervation are significant contributors to arrhythmogenesis following ischemia. 14 The protein c-fos, derived from the immediate-early genes c-fos, is rapidly activated in stimulated neurons and commonly utilized as a marker for neuronal activation. 32 NGF serves as a regulator of nerve growth and is recognized for its ability to promote the aggressive sprouting and remodeling of sympathetic nerves.…”

Section: Pc−cnts Attenuated Sympatheticmentioning

confidence: 99%

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Phospholipid-Coated Carbon Nanotubes as Neuromodulators to Protect against Ventricular Arrhythmias

Xu,

Guo,

Wang

et al. 2023

ACS Appl. Nano Mater.

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Left stellate ganglion (LSG) hyperactivity is a critical factor in ventricular arrhythmias (VAs), and inhibiting LSG activity remains challenging. Carbon nanotubes (CNTs) are gaining popularity as promising nanomedicines for applications in neuromodulation owing to their exceptional physicochemical properties and capacity to interface with neurons and neuronal circuits. We have fabricated multiwalled CNTs coated with 1,2-diphytanoyl-sn-glycero-3-phosphocholine (PC–CNTs) and explored their neuromodulatory effects in protection against VAs. In vitro calcium imaging of HT22 cells demonstrates that PC–CNTs effectively inhibit neuronal activity. In vivo, PC–CNTs are microinjected into the canine LSG in a model of myocardial ischemia. PC–CNTs significantly inhibit LSG neural activity and function, suppress sympathetic nerve indices of heart rate variability, and mitigate myocardial ischemia-induced VAs. Histological analysis of the LSG reveals that PC–CNTs downregulate the levels of c-fos and nerve growth factor. Transcriptomic analysis of the LSG indicates that attenuating neuroinflammation might be the underlying mechanism of the therapeutic effects of PC–CNTs. This study provides compelling evidence that PC–CNTs are potential therapeutic neuromodulators, representing a promising approach to protecting against VAs.

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AIEgen‐Based Covalent Organic Frameworks for Preventing Malignant Ventricular Arrhythmias Via Local Hyperthermia Therapy

Zhang

Guo

et al. 2023

Advanced Materials

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We report the engineering of aggregation‐induced emission luminogens (AIEgen) based covalent organic frameworks (COFs), TDTA‐COF, BTDTA‐COF, and BTDBETA‐COF, as hyperthermia agents for inhibiting the occurrence of malignant ventricular arrhythmias (VAs). These AIE COFs exhibit dual functionality, as they not only directly modulate the function and neural activity of stellate ganglion (SG) through local hyperthermia therapy (LHT) but also induce the browning of white fat and improve the neuro‐inflammation peri‐SG microenvironment, which is favorable for inhibiting ischemia‐induced VAs. In vivo studies have confirmed that BTDBETA‐COF‐mediated LHT enhances thermogenesis and browning‐related gene expression, thereby serving a synergistic role in combating VAs. Transcriptome analysis of peri‐SG adipose tissue reveals a substantial downregulation of inflammatory cytokines, highlighting the potency of BTDBETA‐COF‐mediated LHT in ameliorating the neuro‐inflammation peri‐SG microenvironment and offering myocardial and arrhythmia protection. Our work on AIE COF‐based hyperthermia agent for VAs inhibition providing a new avenue for mitigating cardiac sympathetic nerve hyperactivity.AIEgen; covalent organic frameworks; hyperthermia agent; malignant ventricular arrhythmias; neuromodulationThis article is protected by copyright. All rights reserved

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Metabolism regulator adiponectin prevents cardiac remodeling and ventricular arrhythmias via sympathetic modulation in a myocardial infarction model

Cited by 28 publications

References 59 publications

The sex-dependent response to psychosocial stress and ischaemic heart disease

The sex-dependent response to psychosocial stress and ischaemic heart disease

Phospholipid-Coated Carbon Nanotubes as Neuromodulators to Protect against Ventricular Arrhythmias

AIEgen‐Based Covalent Organic Frameworks for Preventing Malignant Ventricular Arrhythmias Via Local Hyperthermia Therapy

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