The role of inflammation in takotsubo syndrome: A new therapeutic target?

Takotsubo syndrome (TTS) is a particular form of acute heart failure that can be challenging to distinguish from acute coronary syndrome at presentation. TTS was previously considered a benign self-limiting condition, but it is now known to be associated with substantial short- and long-term morbidity and mortality. Because of the poor understanding of its underlying pathophysiology, there are few evidence-based interventions to treat TTS. The hypotheses formulated so far can be grouped into endogenous adrenergic surge, psychological stress or preexisting psychiatric illness, coronary vasospasm with microvascular dysfunction, metabolic and energetic alterations, and inflammatory mechanisms. Current evidence demonstrates that the infiltration of immune cells such as macrophages and neutrophils play a pivotal role in TTS. At baseline, resident macrophages were the dominant subset in cardiac macrophages, however, it underwent a shift from resident macrophages to monocyte-derived infiltrating macrophages in TTS. Depletion of macrophages and monocytes in mice strongly protected them from isoprenaline-induced cardiac dysfunction. It is probable that immune cells, especially macrophages, may be new targets for the treatment of TTS.

Abnormalities in Electroencephalographic Microstates in Patients with Late-Life Depression.

Background: Late-life depression (LLD) is characterized by disrupted brain networks. Resting-state networks in the brain are composed of both stable and transient topological structures known as microstates, which reflect the dynamics of the neural activities. However, the specific pattern of EEG microstate in LLD remains unclear. Methods: Resting-state EEG were recorded for 31 patients with episodic LLD (eLLD), 20 patients with remitted LLD (rLLD) and 32 healthy controls (HCs) using a 64-channel cap. The clinical data of the patients were collected and the 17-Item Hamilton Rating Scale for Depression (HAMD) was used for symptom assessment. Duration, occurrence, time coverage and syntax of the four microstate classes (A-D) were calculated. Group differences in EEG microstates and the relationship between microstates parameters and clinical features were analyzed. Results: Compared with NC and patients with rLLD, patients with eLLD showed increased duration and time coverage of microstate class D. Besides, a decrease in occurrence of microstate C and transition probability between microstate B and C was observed. In addition, the time coverage of microstate D was positively correlated with the total score of HAMD, core symptoms, and miscellaneous items. Conclusion: These findings suggest that disrupted EEG microstates may be associated with the pathophysiology of LLD and may serve as potential state markers for the monitoring of the disease.

Association of composite dietary antioxidant index with mortality in adults with hypertension: evidence from NHANES.

Objective: The objective of this study is to assess the correlation between composite dietary antioxidant index (CDAI) with all-cause mortality and cause-specific mortality in adults with hypertension. Methods: The cohort study comprised adult participants with hypertension from the NHANES database, spanning 9 cycles from 2001 to 2018. Follow-up was conducted until December 31, 2019. Multi-variable Cox regression analysis was utilized to ascertain hazard ratios (HR) and their corresponding 95% confidence intervals, evaluating the relationship between CDAI and the risks of all-cause and cause-specific mortality. To further investigate the association between CDAI and mortality rates in adults with hypertension, Kaplan-Meier survival curves, restricted cubic splines (RCS), subgroup analyses and sensitivity analyses were employed. Results: The analysis included 16,713 adults with hypertension (mean age 56.93 ± 0.23 years, 8,327 [49.61%] male). During the mean follow-up time 102.11 ± 1.22 months, with 3,908 (18.08%) all-cause mortality occurred, 1,082 (4.84%) cardiovascular mortality and 833 (3.80%) cancer mortality. Compared to the lowest quartile of CDAI, the weighted multivariate hazard ratios of participants in the highest quartile was 0.77 (95% CI, 0.68-0.87) for all-cause mortality, 0.83 (95% CI, 0.67-1.04) for cardiovascular mortality, and 0.64 (95% CI, 0.50-0.82) for cancer mortality. RCS analysis demonstrated a nonlinear association of CDAI with all-cause and cancer mortality, and a linear association between CDAI and cardiovascular mortality. The results were robust in subgroup analyses and sensitivity analyses. Conclusion: Higher CDAI is associated with reduced all-cause mortality, cardiovascular mortality, and cancer mortality in hypertensive adults. Our findings highlight the importance of an antioxidant diet in improving outcomes in adults with hypertension.

Hemodynamics and arrhythmia disorder caused by lithium poisoning: A case report. / 锂中毒导致心律失常、血流动力学障碍1例.

Bipolar affective disorder refers to a category of mood disorders characterized clinically by the presence of both manic or hypomanic episodes and depressive episodes. Lithium stands out as the primary pharmacological intervention for managing bipolar affective disorder. However, its therapeutic dosage closely approaches toxic levels. Toxic symptoms appear when the blood lithium concentration surpasses 1.4 mmol/L, typically giving rise to gastrointestinal and central nervous system reactions. Cardiac toxicity is rare but serious in cases of lithium poisoning. The study reports a case of a patient with bipolar affective disorder who reached a blood lithium concentration of 6.08 mmol/L after the patient took lithium carbonate sustained-release tablets beyond the prescribed dosage daily and concurrently using other mood stabilizers. This resulted in symptoms such as arrhythmia, shock, impaired consciousness, and coarse tremors. Following symptomatic supportive treatment, including blood dialysis, the patient's physical symptoms gradually improved. It is necessary for clinicians to strengthen the prevention and recognition of lithium poisoning.

Effects of different exercise methods and intensities on the incidence and prognosis of atrial fibrillation.

Atrial fibrillation (AF), the most common sustained arrhythmia in clinical practice, exhibits a higher risk of cardiovascular adverse events. Exercise plays a crucial role in AF prevention, but the effects of different exercise types and doses are inconclusive. This review aims to comprehensively explore the most recent evidence and possible mechanisms of diverse exercise modalities concerning AF incidence and therapeutic outcomes. Multiple studies underscore the efficacy of moderate-intensity continuous training (MICT) in reducing AF incidence and symptom burden, rendering it the currently favored exercise therapy for AF patients. High-intensity interval training (HIIT) shows promise, potentially surpassing MICT, especially in reducing age-related AF susceptibility and improving symptoms and exercise capacity. Conversely, prolonged high-intensity endurance exercise exacerbates AF risk due to excessive exercise volume, with potential mechanisms encompassing irreversible atrial remodeling, heightened inflammation, and increased vagal tone. In summation, MICT is a secure strategy for populations in mitigating the risk associated with AF incidence and secondary cardiovascular events and should be encouraged. Also, it is recommended to initiate large-scale clinical intervention trials encompassing a variety of exercise types to delineate the optimal exercise prescription for cardiovascular patients, including those afflicted with AF.

Altered resting-state brain oscillation and the associated cognitive impairments in late-life depression with different depressive severity: An EEG power spectrum and functional connectivity study.

OBJECTIVE: Cognitive impairments are prevalent in late-life depression (LLD). However, it remains unclear whether there are concurrent brain oscillation alterations in resting condition across varying level of depression severity. This cross-sectional study aims to investigate the characteristics of altered resting-state oscillations, including power spectrum and functional connectivity, and their association with the cognitive impairments in LLD with different depression severity. METHODS: A total of 65 patients with LLD and 40 elder participants without depression were recruited. Global cognition and subtle cognitive domains were evaluated. A five-minute resting-state electroencephalography (EEG) was conducted under eyes-closed conditions. Measurements included the ln-transformed absolute power for power spectrum analysis and the weighted phase lag index (wPLI) for functional connectivity analysis. RESULTS: Attentional and executive dysfunction were exhibited in Moderate-Severe LLD group. Enhanced posterior upper gamma power was observed in both LLD groups. Additionally, enhanced parietal and fronto-parietal/occipital theta connectivity were observed in Moderate-Severe LLD group, which were associated with the attentional impairment. LIMITATIONS: Limitations include a small sample size, concomitant medication use, and a relatively higher proportion of females. CONCLUSIONS: Current study observed aberrant brain activity patterns in LLD across different levels of depression severity, which were linked to cognitive impairments. The altered posterior brain oscillations may be trait marker of LLD. Moreover, cognitive impairments and associated connectivity alterations were exhibited in moderate-severe group, which may be a state-like marker of moderate-to severe LLD. The study deepens understanding of cognitive impairments with the associated oscillation changes, carrying implications for neuromodulation targets in LLD.

Research Progress on the Role and Mechanism of GDF15 in Body Weight Regulation.

BACKGROUND: Growth differentiation factor-15 (GDF15) is a member of the growth differentiation factor subfamily in the transforming growth factor beta superfamily. GDF15 has multiple functions and can regulate biological processes. High levels of GDF15 in the circulation can affect metabolic processes. Studies have shown that GDF15 is associated with changes in body weight. SUMMARY: This review reviews the current knowledge on the relationship between GDF15 and body weight change, focusing on the role and mechanism of GDF15 in body weight regulation. GDF15 plays an important role in reducing food intake, improving insulin resistance, and breaking down fat, suggesting that GDF15 has an important regulatory effect on body weight. The mechanism by which GDF15 causes reduced food intake may be related to changes in food preference, delayed gastric emptying, and conditioned taste aversion. GDF15 can combat insulin resistance induced by inflammation or protect ß cell from apoptosis. GDF15 probably promotes lipolysis through a brain-somatic tissue circuit. Several factors and related signaling pathways are also mentioned that can contribute to the effects of GDF15 on reducing weight. KEY MESSAGE: GDF15 plays an important role in weight regulation and provides a new direction for the treatment of obesity. Its effects on resisting obesity are of great significance to inhibiting the progression of metabolic diseases. It is expected to become a new target for regulating body weight, improving obesity, and treating metabolic diseases such as diabetes.

Short-chain fatty acids are potential goalkeepers of atherosclerosis.

Short-chain fatty acids (SCFAs) are metabolites produced by gut bacteria and play a crucial role in various inflammatory diseases. Increasing evidence suggests that SCFAs can improve the occurrence and progression of atherosclerosis. However, the molecular mechanisms through which SCFAs regulate the development of atherosclerosis have not been fully elucidated. This review provides an overview of the research progress on SCFAs regarding their impact on the risk factors and pathogenesis associated with atherosclerosis, with a specific focus on their interactions with the endothelium and immune cells. These interactions encompass the inflammation and oxidative stress of endothelial cells, the migration of monocytes/macrophages, the lipid metabolism of macrophages, the proliferation and migration of smooth muscle cells, and the proliferation and differentiation of Treg cells. Nevertheless, the current body of research is insufficient to comprehensively understand the full spectrum of SCFAs' mechanisms of action. Therefore, further in-depth investigations are imperative to establish a solid theoretical foundation for the development of clinical therapeutics in this context.

The Role of Regulatory T Cells in Heart Repair After Myocardial Infarction.

Myocardial infarction (MI) remains one of the leading causes of death worldwide. Inflammation and immune responses after MI are of significance to the adverse cardiac remodeling. Regulatory T cells (Tregs) play an important role in suppressing the immune response and thus benefit the post-MI remodeling. After MI, damaged cardiomyocytes may be replaced by scar tissue, leading to systolic and diastolic dysfunction and subsequently adverse remodeling. In this review, we provide an overview of the function and possible mechanisms of Tregs in post-MI heart repair. Specifically, after the occurrence of MI, Tregs infiltrated to peri-infarcted myocardium through CCR5 pathway, CXCR4-CXCL12 axis, and Hippo pathway. Normal functional Tregs can reduce the size of the MI area, improve heart function, and ameliorate myocardial remodeling by inhibiting proinflammatory cells accumulation, changing the proportion of macrophages phenotypes, improving myocardial fibrosis, protecting myocardial cells, and promoting angiogenesis. Eventually, Functional Tregs recruited into the heart can improve MI outcomes. Therefore, targeted therapies with Tregs might provide a promising approach to the treatment of MI remodeling.

Complex Interplay Between Metabolism and CD4+ T-Cell Activation, Differentiation, and Function: a Novel Perspective for Atherosclerosis Immunotherapy.

Atherosclerosis is a complex pathological process that results from the chronic inflammatory reaction of the blood vessel wall and involves various immune cells and cytokines. An imbalance in the proportion and function of the effector CD4+ T-cell (Teff) and regulatory T-cell (Treg) subsets is an important cause of the occurrence and development of atherosclerotic plaques. Teff cells depend on glycolytic metabolism and glutamine catabolic metabolism for energy, while Treg cells mainly rely on fatty acid oxidation (FAO), which is crucial for determining the fate of CD4+ T cells during differentiation and maintaining their respective immune functions. Here, we review recent research achievements in the field of immunometabolism related to CD4+ T cells, focusing on the cellular metabolic pathways and metabolic reprogramming involved in the activation, proliferation, and differentiation of CD4+ T cells. Subsequently, we discuss the important roles of mTOR and AMPK signaling in regulating CD4+ T-cell differentiation. Finally, we evaluated the links between CD4+ T-cell metabolism and atherosclerosis, highlighting the potential of targeted modulation of CD4+ T-cell metabolism in the prevention and treatment of atherosclerosis in the future.

Regulatory T Cells in Pathological Cardiac Hypertrophy: Mechanisms and Therapeutic Potential.

BACKGROUND: Pathological cardiac hypertrophy is linked to immune-inflammatory injury, and regulatory T cells (Tregs) play a crucial role in suppressing immune-inflammatory responses. However, the precise role of Tregs in pathological cardiac hypertrophy remains unclear. OBJECTIVE: To summarize the current knowledge on the role and mechanisms of Tregs in pathological cardiac hypertrophy and explore their perspectives and challenges as a new therapeutic approach. RESULTS: Treg cells may play an important protective role in pressure overload (hypertension, aortic stenosis), myocardial infarction, metabolic disorders (diabetes, obesity), acute myocarditis, cardiomyopathy (hypertrophic cardiomyopathy, storage diseases), and chronic obstructive pulmonary disease-related pathological cardiac hypertrophy. Although some challenges remain, the safety and efficacy of Treg-based therapies have been confirmed in some clinical trials, and engineered antigen-specific Treg cells may have better clinical application prospects due to stronger immunosuppressive function and stability. CONCLUSION: Targeting the immune-inflammatory response via Treg-based therapies might provide a promising and novel future approach to the prevention and treatment of pathological cardiac hypertrophy.

Deficiency of Tregs in hypertension-associated left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) is the most common target organ damage in hypertension. Abnormal numbers or functions of CD4+ CD25+ Foxp3+ regulatory T lymphocytes (Tregs) can cause immune disorders, which participates in LVH. This study aimed to explore the role of Tregs in LVH by investigating circulating Tregs and associated cytokine levels in hypertensive patients with or without LVH. Blood samples were collected from 83 hypertensive patients without LVH (essential hypertension group, EH), 91 hypertensive patients with LVH (left ventricular hypertrophy group, LVH), and 69 normotensive controls without LVH (control group, CG). Tregs and cytokines were measured by flow cytometry and enzyme-linked immunosorbent assays. We found that circulating Tregs were significantly lower in hypertensive patients than in CG subjects. It was lower in LVH than in EH patients. No correlation between blood pressure regulation and Tregs was found in EH or LVH patients. Furthermore, Tregs in older females were lower than those in older males among LVH patients. Additionally, serum interleukin-10 (IL-10) and transforming growth factor beta 1 (TGFß1) decreased in hypertensive patients, and interleukin-6 (IL-6) increased in LVH patients. Tregs were negatively correlated with creatine kinase, low-density lipoprotein cholesterol, apoprotein B, high-sensitivity C-reactive protein, and left ventricular mass index (LVMI) values. In general, our study demonstrates significantly decreased circulating Tregs in hypertensive LVH patients. Decreased circulating Tregs in LVH is independent of blood pressure regulation. IL-6, IL-10, and TGF-ß1 are related with LVH in hypertension.

Arterial remodeling: the role of mitochondrial metabolism in vascular smooth muscle cells.

Arterial remodeling is a common pathological basis of cardiovascular diseases such as atherosclerosis, vascular restenosis, hypertension, pulmonary hypertension, aortic dissection, and aneurysm. Vascular smooth muscle cells (VSMCs) are not only the main cellular components in the middle layer of the arterial wall but also the main cells involved in arterial remodeling. Dedifferentiated VSMCs lose their contractile properties and are converted to a synthetic, secretory, proliferative, and migratory phenotype, playing key roles in the pathogenesis of arterial remodeling. As mitochondria are the main site of biological oxidation and energy transformation in eukaryotic cells, mitochondrial numbers and function are very important in maintaining the metabolic processes in VSMCs. Mitochondrial dysfunction and oxidative stress are novel triggers of the phenotypic transformation of VSMCs, leading to the onset and development of arterial remodeling. Therefore, pharmacological measures that alleviate mitochondrial dysfunction reverse arterial remodeling by ameliorating VSMCs metabolic dysfunction and phenotypic transformation, providing new options for the treatment of cardiovascular diseases related to arterial remodeling. This review summarizes the relationship between mitochondrial dysfunction and cardiovascular diseases associated with arterial remodeling and then discusses the potential mechanism by which mitochondrial dysfunction participates in pathological arterial remodeling. Furthermore, maintaining or improving mitochondrial function may be a new intervention strategy to prevent the progression of arterial remodeling.

Improvement of hemodynamic parameters in aortic stenosis patients with transcatheter valve replacement by using impedance cardiography.

Background: The hemodynamic changes of patients with aortic stenosis (AS) who underwent transcatheter valve replacement (TAVR) have not been completely investigated. Methods and results: We enrolled 74 patients with AS who underwent TAVR and assessed cardiac function changes at 1 week post-operation by impedance cardiography (ICG) in a supine position at rest for more than 15 min. Of the 74 patients, 47 had preserved left ventricular ejection fraction (LVEF ≥ 50%; preserved-LVEF group) and 27 had reduced LVEF (LVEF <50%; reduced-LVEF group). TAVR improved the cardiac structure and function, as evidenced by the decrease in the left ventricular end-diastolic (LVED), left atrial diameter (LAD), and an increase in the LVEF. We observed a decrease in N-terminal pro-brain natriuretic peptide (NT-proBNP) level compared to that before treatment. Moreover, patients with reduced LVEF had a more significant reduction of NT-proBNP than those with preserved LVEF. Meanwhile, the blood pressure of patients had no significant differences pre- and post-operation. Based on ICG, there were no changes in the parameter of cardiac preload [thoracic fluid content (TFC)]. We observed an improvement in parameters of diastolic cardiac function [left ventricular ejection time (LVET) and pre-ejection period (PEP)]. And we detected converse results in parameters of heart systolic function [systolic time ratio (STR), cardiac output (CO), cardiac index (CI), stroke index (SI), and stroke volume (SV)] and cardiac afterload [stroke systemic vascular resistance (SSVR) and SSVR-index (SSVRI)]. In addition, TFC level was decreased in patients with thoracic volume overload after valve replacement. Subgroup analysis showed that the changes in those parameters were more noticeable in patients with reduced LVEF than that with preserved LVEF. Moreover, we observed no effects on parameters of heart systolic function and heart afterload in the LVEF ≥ 50% group before and after TAVR. Conclusion: Our data revealed a beneficial effect of TAVR in diastolic function and preload as detected by the ICG. But the LV systolic function and cardiac afterload were not improved in patients with LVEF <50%. The result indicated that ICG could be used as an important technique to monitor the cardiac condition of patients after aortic valve replacement.

Research progress on Th17 and T regulatory cells and their cytokines in regulating atherosclerosis.

Background: Coronary heart disease due to atherosclerosis is the leading cause of death worldwide. Atherosclerosis is considered a chronic inflammatory state in the arterial wall that promotes disease progression and outcome, and immune cells play an important role in the inflammatory process. Purpose: We review the mechanisms of CD4+ T subsets, i.e., helper T17 (Th17) cells and regulatory T cells (Tregs), in regulating atherosclerosis, focusing on the role of interleukin (IL)-17, IL-10, and other cytokines in this disease and the factors influencing the effects of these cytokines. Results: IL-17 secreted by Th17 cells can promote atherosclerosis, but few studies have reported that IL-17 can also stabilize atherosclerotic plaques. Tregs play a protective role in atherosclerosis, and Th17/Treg imbalance also plays an important role in atherosclerosis. Conclusion: The immune response is important in regulating atherosclerosis, and studying the mechanism of action of each immune cell on atherosclerosis presents directions for the treatment of atherosclerosis. Nevertheless, the current studies are insufficient for elucidating the mechanism of action, and further in-depth studies are needed to provide a theoretical basis for clinical drug development.

Effects of early phase 1 cardiac rehabilitation on cardiac function evaluated by impedance cardiography in patients with coronary heart disease and acute heart failure.

Purpose: The purpose of the study was to access the impact of phase 1 cardiac rehabilitation (CR) on cardiac function and hemodynamic changes in patients with coronary heart disease (CHD) and acute heart failure (AHF). Materials and methods: A total of 98 patients with CHD and AHF were recruited and randomized into two groups. Control group received standard pharmacotherapy and CR group received standard pharmacotherapy combined phase 1 CR. NT-proBNP and hemodynamic parameters measured by impedance cardiography (ICG) were estimated at baseline and at the end of treatment period. Results: Phase 1 CR combined routine medical treatment could lower NT-proBNP levels. The percentage of high-risk patients was significantly decreased in CR group, although the post-treatment NT-proBNP level between control group and CR group showed no significant differences. Similarly, most hemodynamic parameters improved in the CR group, but not in the control group, suggesting that phase 1 CR in combination with the standard pharmacotherapy improved hemodynamic characteristics by elevating cardiac output, ameliorating preload, improving systolic and diastolic function, and relieving afterload, although the post-treatment hemodynamic parameters showed no statistically significant differences between the control group and the CR group. Conclusion: Phase 1 CR combined routine medication can improve cardiac function and hemodynamic characteristics in patients with CHD and AHF. Thus, recommendation of phase 1 CR to stable patients is necessary.

New insights into macrophage subsets in atherosclerosis.

Macrophages in atherosclerotic patients are notably plastic and heterogeneous. Single-cell RNA sequencing (Sc RNA-seq) can provide information about all the RNAs in individual cells, and it is used to identify cell subpopulations in atherosclerosis (AS) and reveal the heterogeneity of these cells. Recently, some findings from Sc RNA-seq experiments have suggested the existence of multiple macrophage subsets in atherosclerotic plaque lesions, and these subsets exhibit significant differences in their gene expression levels and functions. These cells affect various aspects of plaque lesion development, stabilization, and regression, as well as plaque rupture. This article aims to review the content and results of current studies that used RNA-seq to explore the different types of macrophages in AS and the related molecular mechanisms as well as to identify the potential roles of these macrophage types in the pathogenesis of atherosclerotic plaques. Also, this review listed some new therapeutic targets for delaying atherosclerotic lesion progression and treatment based on the experimental results.

Lipoprotein(a), a Lethal Player in Calcific Aortic Valve Disease.

Calcified aortic valve disease (CAVD) is the most common valvular cardiovascular disease with increasing incidence and mortality. The primary treatment for CAVD is surgical or transcatheter aortic valve replacement and there remains a lack of effective drug treatment. Recently, lipoprotein (a) (Lp(a)) has been considered to play a crucial role in CAVD pathophysiology. Multiple studies have shown that Lp(a) represents an independent risk factor for CAVD. Moreover, Lp(a) mediates the occurrence and development of CAVD by affecting aortic valve endothelial dysfunction, indirectly promoting foam cell formation through oxidized phospholipids (OxPL), inflammation, oxidative stress, and directly promotes valve calcification. However, there is a lack of clinical trials with Lp(a) reduction as a primary endpoint. This review aims to explore the relationship and mechanism between Lp(a) and CAVD, and focuses on the current drugs that can be used as potential therapeutic targets for CAVD.

The Effect of Enhanced External Counterpulsation on Platelet Aggregation in Patients with Coronary Heart Disease.

BACKGROUND: Resistance to antiplatelet therapy, especially aspirin or clopidogrel, triggers other therapies for patients with coronary heart disease (CHD). Enhanced external counterpulsation (EECP) is a noninvasive, pneumatic technique that provides beneficial effects for patients with CHD. However, the physiological effects of EECP have not been fully studied, and the role of EECP on platelet function remains poorly understood. METHODS: A total of 168 patients with CHD were finally selected from the Second Xiangya Hospital and randomly assigned to either a control group or EECP group. The control group accepted only standard medical treatment, while the EECP group accepted standard medical treatment and EECP treatment. Blood samples were collected from patients at baseline and after EECP, and platelet aggregation was assessed. Changes in platelet aggregation were compared before and after treatment. RESULTS: There was no difference in the basal levels of arachidonic acid (AA) induced platelet maximum aggregation ratio (MAR) between the two groups. The AA-induced platelet MAR was significantly decreased after EECP therapy. The logistic analysis showed that low HDL-C was not favorable for the decrease in platelet aggregation. CONCLUSION: EECP therapy is favorable for lowering platelet aggregation in patients with CHD, especially the AA-induced platelet aggregation ratio.

New insights into the roles of glucocorticoid signaling dysregulation in pathological cardiac hypertrophy.

Pathological cardiac hypertrophy is a process of abnormal remodeling of the myocardium in response to stress overload or ischemia that results in myocardial injury, which is an independent risk factor for the increased morbidity and mortality of heart failure. Elevated circulating glucocorticoids (GCs) levels are associated with an increased risk of pathological cardiac hypertrophy, but the exact role remains unclear. In the heart, GCs exerts physiological and pharmacological effects by binding the glucocorticoid receptor (GR, NR3C1). However, under the state of tissue damage or oxidative stress, GCs can also bind the closely related mineralocorticoid receptor (MR, NR3C2) to exert a detrimental effect on cardiac function. In addition, the bioavailability of GCs at the cellular level is mainly regulated by tissue-specific metabolic enzymes 11ß-hydroxysteroid dehydrogenases (11ß-HSDs), including 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) and type 2 (11ß-HSD2), which catalyze the interconversion of active GCs. In this paper, we provide an overview of GC signaling and its physiological roles in the heart and highlight the dynamic and diverse roles of GC signaling dysregulation, mediated by excessive ligand GCs levels, GR/MR deficiency or overexpression, and local GCs metabolic disorder by 11ß-HSDs, in the pathology of cardiac hypertrophy. Our findings will provide new ideas and insights for the search for appropriate intervention targets for pathological cardiac hypertrophy.