Microglia-Mediated Neuroinflammation: A Potential Target for the Treatment of Cardiovascular Diseases.
Journal of inflammation research
Microglia are tissue-resident macrophages of the central nervous system (CNS). In the CNS, microglia play an important role in the monitoring and intervention of synaptic and neuron-level activities. Interventions targeting microglia have been shown to improve the prognosis of various neurological diseases. Recently, studies have observed the activation of microglia in different cardiovascular diseases. In addition, different approaches that regulate the activity of microglia have been shown to modulate the incidence and progression of cardiovascular diseases. The change in autonomic nervous system activity after neuroinflammation may be a potential intermediate link between microglia and cardiovascular diseases. Here, in this review, we will discuss recent updates on the regulatory role of microglia in hypertension, myocardial infarction and ischemia/reperfusion injury. We propose that microglia serve as neuroimmune modulators and potential targets for cardiovascular diseases.
10.2147/JIR.S350109
Subarachnoid Hemorrhage From Cavernous Malformation Masquerading as Myocardial Infarction.
Journal of medical cases
Intracranial hemorrhage, including subarachnoid hemorrhage (SAH), is associated with many cardiac effects, including cardiac rhythm abnormalities, ischemic electrocardiographic (ECG) changes, elevated cardiac troponin levels, and regional wall motion abnormalities on echocardiogram. About 40% of patients with SAH demonstrate increased serum markers for myocardial necrosis. Approximately 10% of patients with SAH demonstrate left ventricular (LV) wall motion abnormalities; a subset of these patients will have irreversible myocardial damage, but most regain LV function in several weeks. Cardiac effects of SAH are thought to be a result of an imbalance of the autonomic nervous system with resultant increased catecholamine effect on the myocardial cells rather than due to preexisting coronary artery disease. These cardiovascular complications carry a prognostic significance in patients with SAH and can also be misdiagnosed as primary cardiac problems and delay the diagnosis of SAH. Herein, we present a case of a 68-year-old female who presented to the emergency department with acute onset of upper back and neck pain. She was initially misdiagnosed with myocardial infarction in view of the ischemic changes in the ECG and elevated cardiac troponins. She was started on antiplatelets and anticoagulation but was later found to have a negative coronary angiography and was diagnosed with SAH via a computed tomography (CT) scan. Intracranial hemorrhage can be associated with elevated cardiac enzymes and ECG changes and can sometimes masquerade as an acute coronary syndrome (ACS). A careful history and examination and a high index of clinical suspicion are pivotal in such cases since early diagnosis significantly impacts prognosis and prevents the inadvertent use of antiplatelets and anticoagulation, which can be detrimental if used in such cases.
10.14740/jmc4064
Cerebral blood flow alteration following acute myocardial infarction in mice.
Kaplan Abdullah,Yabluchanskiy Andriy,Ghali Rana,Altara Raffaele,Booz George W,Zouein Fouad A
Bioscience reports
Heart failure is associated with low cardiac output (CO) and low brain perfusion that imposes a significant risk for accelerated brain ageing and Alzheimer's disease (AD) development. Although clinical heart failure can emerge several years following acute myocardial infarction (AMI), the impact of AMI on cerebral blood flow (CBF) at early stages and up to 30 days following MI is unknown. Sixteen months old male mice underwent left anterior descending (LAD) coronary artery ligation. Hemodynamics analyses were performed at baseline and at days 1, 7, and 30 post-MI. Left ventricular (LV) ejection fraction (EF), LV volumes, CO, and right common carotid artery (RCCA) diameter were recorded by echocardiography. RCCA flow (RCCA FL) was measured by Doppler echocardiography. LV volumes consistently increased (<0.0012) and LV systolic function progressively deteriorated (<0.0001) post-MI. CO and RCCA FL showed a moderate but significant decrease over the course of MI with similar fluctuation pattern such that both variables were decreased at day 1, increased at day 7, and decreased at 30 days post-MI. Correlation and regression analyses between CO and RCCA FL showed a strong correlation with significance at baseline and day 30 post-MI ( = 0.71, =0.03, and = 0.72, =0.03, respectively). Days 1 and 7 analyses between CO and RCCA FL showed moderate correlation with non-significance post-MI ( = 0.51, =0.2, and = 0.56, =0.12, respectively). In summary, CBF significantly decreased following AMI and remained significantly decreased for up to 30 days, suggesting a potential risk for brain damage that could contribute to cognitive dysfunction later in life.
10.1042/BSR20180382
Reward system activation improves recovery from acute myocardial infarction.
Nature cardiovascular research
Psychological processes have a crucial role in the recovery from acute myocardial infarction (AMI), yet the underlying mechanisms of these effects remain elusive. Here we demonstrate the impact of the reward system, a brain network associated with motivation and positive expectations, on the clinical outcomes of AMI in mice. Chemogenetic activation of dopaminergic neurons in the reward system improved the remodeling processes and vascularization after AMI, leading to enhanced cardiac performance compared to controls. These effects were mediated through several physiological mechanisms, including alterations in immune activity and reduced adrenergic input to the liver. We further demonstrate an anatomical connection between the reward system and the liver, functionally manifested by altered transcription of complement component 3, which in turn affects vascularization and recovery from AMI. These findings establish a causal connection between a motivational brain network and recovery from AMI, introducing potential therapeutic avenues for intervention.
10.1038/s44161-024-00491-3
Vagal Nerve Stimulation Reduces Ventricular Arrhythmias and Mitigates Adverse Neural Cardiac Remodeling Post-Myocardial Infarction.
JACC. Basic to translational science
This study sought to evaluate the impact of chronic vagal nerve stimulation (cVNS) on cardiac and extracardiac neural structure/function after myocardial infarction (MI). Groups were control, MI, and MI + cVNS; cVNS was started 2 days post-MI. Terminal experiments were performed 6 weeks post-MI. MI impaired left ventricular mechanical function, evoked anisotropic electrical conduction, increased susceptibility to ventricular tachycardia and fibrillation, and altered neuronal and glial phenotypes in the stellate and dorsal root ganglia, including glial activation. cVNS improved cardiac mechanical function and reduced ventricular tachycardia/ventricular fibrillation post-MI, partly by stabilizing activation/repolarization in the border zone. MI-associated extracardiac neural remodeling, particularly glial activation, was mitigated with cVNS.
10.1016/j.jacbts.2023.03.025
The cardioprotective and anxiolytic effects of Chaihujialonggumuli granule on rats with anxiety after acute myocardial infarction is partly mediated by suppression of CXCR4/NF-κB/GSDMD pathway.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
AIMS:Over-expression of CXCR4 activates nuclear translocation of NF-κB, induces high expression of NLRP3, GSDMD, IL-1β and IL-18, which promotes severe inflammatory response following myocardial infarction. Previous studies revealed inflammation induces anxiety after myocardial infarction. The Chaihujialonggumuli granule has anti-inflammatory properties and could tranquillize mind. But the mechanism of its efficacy remains unknown. This study was to investigate the possible mechanism of BFG on cardioprotective and anxiolytic. METHODS:The expression of CXCR4, NF-κB, NLRP3and GSDMD was measured with western-blot, QRT-PCR. The expression location of CXCR4, NLRP3, GSDMD were determined by immunohistochemistry. IL-1β、IL-18 in the peripheral blood were measured by ELISA. HE staining, Masson staining and transmission electron microscopy were used to observe morphological changes of cardiomyocytes. Echocardiography was used to assess cardiac function after cardiac surgery. Elevated cross maze test and open field test were used to evaluate behaviours. Western blot was used to detect the protein expressions of 5-HT, DA, IL-1β, IL-18 and neuron damage was investigated by Nissl staining in the hippocampus. RESULTS:The up-regulation of CXCR4, NF-κB, NLRP3 and GSDMD were found in the infarcted area after left coronary artery ligation. Pathological staining and analysis showed that more severe inflammatory cytokines infiltration, myocardial fibrosis, were found in myocardial tissue of the complex group rats. And when compared to the sham group, the levels of IL-1β, IL-18 was increased of the complex group in both peripheral blood and brain. Behavioural test and echocardiography indicated that the rats in complex group exploration behaviours was significantly reduced, and with poor cardiac functional recovery. The AMD3100 had an inhibitory impact of CXCR4 on the activition of its downstream effectors, alleviating inflammatory reaction. Furthermore, the BFG decreased the expression level of CXCR4, NF-κB, GSDMD, NLRP3 in the infarcted area after myocardial infarction, when compared to the complex group. The assays in the brain indicated the BFG suppressed expression and activity of IL-1β, IL-18, and improved 5-HT and DA synthesis. CONCLUSIONS:In sum, our study indicated that BFG may reduce inflammation, treat co-existing anxiety after myocardial infarction through inhibition of CXCR4/NF-κB/GSDMD signalling.
10.1016/j.biopha.2020.111015
Sympathetic Nervous System Mediates Cardiac Remodeling After Myocardial Infarction in a Circadian Disruption Model.
Wang Yuhong,Jiang Wanli,Chen Hu,Zhou Huixin,Liu Zhihao,Liu Zihan,Liu Zhihao,Zhou Yuyang,Zhou Xiaoya,Yu Lilei,Jiang Hong
Frontiers in cardiovascular medicine
Circadian rhythms have a considerable impact on the daily physiology of the heart, and their disruption causes pathology. Several studies have revealed that circadian disruption impaired cardiac remodeling after myocardial infarction (MI); however, the underlying brain-heart mechanisms remain unknown. We aim to discuss whether circadian disruption facilitates cardiac remodeling after MI by activating sympathetic nervous system. Rats were randomly divided into three groups: Sham group (Sham), MI group (MI), and MI+ circadian disruption group (MI+Dis); rats were treated with pseudorabies virus (PRV) injections for trans-synaptic retrograde tracing; rats were randomly divided into two groups: MI+ circadian disruption + Empty Vector+ clozapine N-oxide (CNO) (Empty Vector), and MI+ circadian disruption + hM4D(Gi)+ CNO [hM4D(Gi)]. Circadian disruption significantly facilitated cardiac remodeling after MI with lower systolic function, larger left ventricular volume, and aggravated cardiac fibrosis. Cardiac sympathetic remodeling makers and serum norepinephrine levels were also significantly increased by circadian disruption. PRV virus-labeled neurons were identified in the superior cervical ganglion (SCG), paraventricular nucleus (PVN), and suprachiasmatic nucleus (SCN) regions. Ganglionic blockade via designer receptors exclusively activated by designer drugs (DREADD) technique suppressed the activity of sympathetic nervous system and significantly alleviated the disruption-related cardiac dysfunction. Circadian disruption adversely affected cardiac remodeling after MI possibly by activating sympathetic nervous system, and suppressing sympathetic activity can attenuate this disruption-related cardiac dysfunction.
10.3389/fcvm.2021.668387
The role of central autonomic nervous system dysfunction in Takotsubo syndrome: a systematic review.
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
INTRODUCTION:Takotsubo syndrome (TTS), also known as stress cardiomyopathy or "broken heart" syndrome, is a mysterious condition that often mimics an acute myocardial infarction. Both are characterized by left ventricular systolic dysfunction. However, this dysfunction is reversible in the majority of TTS patients. PURPOSE:Recent studies surprisingly demonstrated that TTS, initially perceived as a benign condition, has a long-term prognosis akin to myocardial infarction. Therefore, the health consequences and societal impact of TTS are not trivial. The pathophysiological mechanisms of TTS are not yet completely understood. In the last decade, attention has been increasingly focused on the putative role of the central nervous system in the pathogenesis of TTS. CONCLUSION:In this review, we aim to summarize the state of the art in the field of the brain-heart axis, regional structural and functional brain abnormalities, and connectivity aberrancies in TTS.
10.1007/s10286-021-00844-z
The Impact of Mental Stress on Cardiovascular Health-Part II.
Journal of clinical medicine
Endothelial dysfunction is one of the earliest manifestations of atherosclerosis, contributing to its development and progression. Mental stress induces endothelial dysfunction through increased activity of the sympathetic nervous system, release of corticotropin-releasing hormone from the hypothalamus, inhibition of nitric oxide (NO) synthesis by cortisol, and increased levels of pro-inflammatory cytokines. Mental-stress-induced increased output of the sympathetic nervous system and concomitant withdrawal of the parasympathetic inflammatory reflex results in systemic inflammation and activation of a neural-hematopoietic-arterial axis. This includes the brainstem and subcortical regions network, bone marrow activation, release of leukocytes into the circulation and their migration to the arterial wall and atherosclerotic plaques. Low-grade, sterile inflammation is involved in all steps of atherogenesis, from coronary plaque formation to destabilisation and rupture. Increased sympathetic tone may cause arterial smooth-muscle-cell proliferation, resulting in vascular hypertrophy, thus contributing to the development of hypertension. Emotional events also cause instability of cardiac repolarisation due to brain lateralised imbalance of cardiac autonomic nervous stimulation, which may lead to asymmetric repolarisation and arrhythmia. Acute emotional stress can also provoke severe catecholamine release, leading to direct myocyte injury due to calcium overload, known as myocytolysis, coronary microvascular vasoconstriction, and an increase in left ventricular afterload. These changes can trigger a heart failure syndrome mimicking acute myocardial infarction, characterised by transient left ventricular dysfunction and apical ballooning, known as stress (Takotsubo) cardiomyopathy. Women are more prone than men to develop mental-stress-induced myocardial ischemia (MSIMI), probably reflecting gender differences in brain activation patterns during mental stress. Although guidelines on CV prevention recognise psychosocial factors as risk modifiers to improve risk prediction and decision making, the evidence that their assessment and treatment will prevent CAD needs further evaluation.
10.3390/jcm11154405
Impact of Ghrelin on Ventricular Arrhythmia and Related Mechanism After Myocardial Infarction.
Pharmacology
INTRODUCTION:Ghrelin is an endogenous peptide with potential protective effects on ischemic heart. METHODS:Synthetic ghrelin was administered (100 μg·kg-1 subcutaneous injection, twice daily) for 4 weeks in a rat model of myocardial infarction (MI) with coronary artery occlusion. At the 5th week, electrocardiogram, monophasic action potentials and autonomic nerve function were evaluated. Cardiac tyrosine hydroxylase (TH) was determined by immunofluorescence staining. RESULTS:MI significantly increased sympathetic nerve activity (SNA) and ventricular arrhythmias, and prolonged APD dispersion and APD alternans (p < 0.01). Ghrelin treatment significantly increased ventricular fibrillation threshold (VFT), shortened APD dispersion and APD alternans, inhibited SNA and promoted vagus nerve activities (p < 0.01). Ghrelin also markedly reversed abnormal expression of TH in the peri-infarcted area of the heart (p < 0.01). DISCUSSION/CONCLUSION:Ghrelin provides a sustained electrophysiological protection by the increase of VFT and improvement of APD dispersion and APD alternans. The mechanism may be related to the regulation of autonomic nerve and sympathetic nerve remodeling. Thus, ghrelin represents a novel drug to prevent ventricular arrhythmia in ischemic heart disease.
10.1159/000519330
Impact of antidepressant use on the autonomic nervous system: A meta-analysis and systematic review.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
Changes in cardiac autonomic nervous system (ANS) regulation observed in psychiatric disorders may be mitigated by antidepressants. We meta-analyzed and systematically reviewed studies examining antidepressants' effects on ANS outcomes, including heart rate variability (HRV). We conducted a PRISMA/MOOSE-compliant search of PubMed and Scopus until March 28th, 2022. We included randomized placebo-controlled trials (RCTs) and pre-post studies, regardless of diagnosis. We pooled results in random-effects meta-analyses, pooling homogeneous study designs and outcomes. We conducted sensitivity analyses and assessed quality of included studies. Thirty studies could be meta-analyzed. Selective serotonin reuptake inhibitors (SSRIs) were significantly associated with a reduction in the square root of the mean-squared difference between successive R-R intervals (RMSSD) (SMD= -0.48) and skin conductance response (SMD= -0.55) in RCTs and with a significant increase in RMSSD in pre-post studies (SMD=0.27). In pre-post studies, tricyclic antidepressants (TCAs) were associated with a significant decrease in several HRV outcomes while agomelatine was associated with a significant increase in high frequency power (SMD= 0.14). In conclusion, SSRIs reduce skin conductance response but have no or inconclusive effects on other ANS outcomes, depending on study design. TCAs reduce markers of parasympathetic function while agomelatine might have the opposite effect. Studies are needed to investigate the impact of SSRIs on the recovery of cardiac ANS regulation after acute myocardial infarction, and the effects of newer antidepressants.
10.1016/j.euroneuro.2023.03.013