This article reviews the role of different types of T lymphocyte subpopulations in pathological cardiac fibrosis remodeling. T helper 17 (Th17) cells are implicated in promoting the development of pathological cardiac fibrosis remodeling, while regulatory T (Treg) cells exert an immunosuppressive functions as negative regulators, attributing to their interleukin-10 (IL-10) secretion and functional phenotype. Th1 and Th2 cells are involved in different stages of the inflammatory response in pathological cardiac fibrosis remodeling, and their influence varies according to the pathological mechanisms of different cardiac diseases. In addition, CD8⁺ T cells regulate the activation and polarization of macrophages, promote the secretion of granzyme B, induce cardiomyocyte apoptosis, and aggravate cardiac fibrosis post-myocardial infarction. Considering the limitation of cytokine modulation in clinical therapy of heart failure, targeting T-cell co-stimulatory molecules emerges as a promising strategy for treating pathologic cardiac remodeling. Future research will explore chimeric antigen receptor modified T cells (CAR-T cells) technology and targeted regulation of Treg cells quantity and phenotype, for both of which have the potential to become effective methods for treating heart disease.
Humans ; Fibrosis ; T-Lymphocytes, Regulatory/immunology* ; Ventricular Remodeling/immunology* ; Myocardium/immunology* ; Animals ; Th17 Cells/immunology* ; Interleukin-10/metabolism* ; Th1 Cells/immunology* ; Th2 Cells/immunology*

The study was conducted to investigate the mechanism of Xinyang Tablets( XYP) in modulating the fat mass and obesity-associated protein(FTO)/N6-methyladenosine(m6A) signaling pathway to ameliorate ventricular remodeling in heart failure(HF). A mouse model of HF was established by transverse aortic constriction(TAC). Mice were randomized into sham, model, XYP(low, medium, and high doses), and positive control( perindopril) groups(n= 10). From day 3 post-surgery, mice were administrated with corresponding drugs by gavage for 6 consecutive weeks. Following the treatment, echocardiography was employed to evaluate the cardiac function, and RT-qPCR was employed to determine the relative m RNA levels of key markers, including atrial natriuretic peptide( ANP), B-type natriuretic peptide( BNP), β-myosin heavy chain(β-MHC), collagen type I alpha chain(Col1α), collagen type Ⅲ alpha chain(Col3α), alpha smooth muscle actin(α-SMA), and FTO. The cardiac tissue was stained with Masson's trichrome and wheat germ agglutinin(WGA) to reveal the pathological changes. Immunohistochemistry was employed to detect the expression levels of Col1α, Col3α, α-SMA, and FTO in the myocardial tissue. The m6A modification level in the myocardial tissue was measured by the m6A assay kit. An H9c2 cell model of cardiomyocyte injury was induced by angiotensin Ⅱ(AngⅡ), and small interfering RNA(siRNA) was employed to knock down FTO expression. RT-qPCR was conducted to assess the relative m RNA levels of FTO and other genes associated with cardiac remodeling. The m6A modification level was measured by the m6A assay kit, and Western blot was employed to determine the phosphorylated phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K) and phosphorylated serine/threonine kinase(p-Akt)/serine/threonine kinase(Akt) ratios in cardiomyocytes. The results of animal experiments showed that the XYP treatment significantly improved the cardiac function, reduced fibrosis, up-regulated the m RNA and protein levels of FTO, and lowered the m6A modification level compared with the model group. The results of cell experiments showed that the XYP-containing serum markedly up-regulated the m RNA level of FTO while decreasing the m6A modification level and the p-PI3K/PI3K and p-Akt/Akt ratios in cardiomyocytes. Furthermore, FTO knockdown reversed the protective effects of XYP-containing serum on Ang Ⅱ-induced cardiomyocyte hypertrophy. In conclusion, XYP may ameliorate ventricular remodeling by regulating the FTO/m6A axis, thereby inhibiting the activation of the PI3K/Akt signaling pathway.
Animals ; Ventricular Remodeling/drug effects* ; Heart Failure/physiopathology* ; Signal Transduction/drug effects* ; Mice ; Male ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Adenosine/analogs & derivatives* ; Myocytes, Cardiac/metabolism* ; Disease Models, Animal

OBJECTIVES: To compare perioperative and mid-term results of multiple versus single arterial off-pump coronary artery bypass grafting (OPCABG) in patients with impaired left ventricular function. METHODS: This study was conducted among 86 patients with a left ventricular ejection fraction (LVEF) <50%, who underwent OPCABG at our hospital between January, 2018 and December, 2021. Of these patients, 22 underwent OPCABG with multiple arterial grafts (multiple graft group) and 64 received a single arterial graft in OPCABG (single graft group). The preoperative, intraoperative, and perioperative data were collected, and the patients were followed up for a mean of 29.28±14.84 months. The perioperative outcomes and follow-up results of the patients were compared, and the factors influencing major adverse cardiovascular events (MACE) were identified using logistic regression. Kaplan-Meier analysis was used to compare the postoperative survival rate without MACE. RESULTS: The patients in multiple graft group had a significantly younger age than those in single graft group (P<0.05), but the other baseline data were similar between the two groups (P>0.05). Perioperative mortality, 24-h postoperative drainage volume, length of ICU stay, intubation time, and the incidence of new-onset atrial fibrillation were all similar between the two groups (P>0.05), but the rate of postoperative hypotension was significantly higher in multiple graft group (34.78% vs 11.54%, P=0.009). No significant differences were found in the incidence of MACE or echocardiographic data during the follow-up. Logistic regression identified the female sex (OR: 0.191, 95% CI: 0.049-0.075) and creatinine level (OR: 1.016, 95% CI: 1.000-1.033) as factors affecting postoperative MACE occurrence. Kaplan-Meier analysis showed no significant difference in MACE-free survival rate between the two groups. CONCLUSIONS OPCABG with multiple arterial grafts does not increase severe perioperative complications or the risk of mid-term MACE in patients with impaired left ventricular function.
Humans ; Follow-Up Studies ; Postoperative Complications/epidemiology* ; Ventricular Dysfunction, Left/physiopathology* ; Coronary Artery Bypass, Off-Pump/adverse effects* ; Male ; Female ; Ventricular Function, Left ; Middle Aged ; Risk Factors ; Aged ; Perioperative Period ; Stroke Volume

OBJECTIVES: To develop a risk prediction model for left ventricular adverse remodeling (LVAR) based on cardiac magnetic resonance (CMR) parameters in patients undergoing percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 329 acute STEMI patients undergoing primary PCI at 8 medical centers from January, 2018 to December, 2021 were prospectively enrolled. The parameters of CMR, performed at 7±2 days and 6 months post-PCI, were analyzed using CVI42 software. LVAR was defined as an increase >20% in left ventricular end-diastolic volume or >15% in left ventricular end-systolic volume at 6 months compared to baseline. The patients were randomized into training (n=230) and validation (n=99) sets in a 7∶3 ratio. In the training set, potential predictors were selected using LASSO regression, followed by univariate and multivariate logistic regression to construct a nomogram. Model performance was evaluated using receiver-operating characteristic (ROC) curves, area under the curve (AUC), calibration curves, and decision curve analysis. RESULTS: LVAR occurred in 100 patients (30.40%), who had a higher incidence of major adverse cardiovascular events than those without LVAR (58.00% vs 16.16%, P<0.001). Left ventricular global longitudinal strain (LVGLS; OR=0.76, 95% CI: 0.61-0.95, P=0.015) and left atrial active strain (LAAS; OR=0.78, 95% CI: 0.67-0.92, P=0.003) were protective factors for LVAR, while infarct size (IS; OR=1.05, 95% CI: 1.01-1.10, P=0.017) and microvascular obstruction (MVO; OR=1.26, 95% CI: 1.01-1.59, P=0.048) were risk factors for LVAR. The nomogram had an AUC of 0.90 (95% CI: 0.86-0.94) in the training set and an AUC of 0.88 (95% CI: 0.81-0.94) in the validation set. CONCLUSIONS LVGLS, LAAS, IS, and MVO are independent predictors of LVAR in STEMI patients following PCI. The constructed nomogram has a strong predictive ability to provide assistance for management and early intervention of LVAR.
Humans ; Percutaneous Coronary Intervention ; Prospective Studies ; ST Elevation Myocardial Infarction/diagnostic imaging* ; Ventricular Remodeling ; Magnetic Resonance Imaging ; Male ; Female ; Middle Aged ; Risk Factors ; Aged ; Risk Assessment

Astragali Radix (AR) and Notoginseng Radix et Rhizoma (NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair (AN) in improving cardiac remodeling and its underlying mechanism remains unclear. This study aimed to evaluate AN's cardioprotective effect and potential mechanism on cardiac remodeling using transverse aortic constriction (TAC) in mice and angiotensin II (Ang II)-induced neonatal rat cardiomyocytes (NRCMs) and fibroblasts in vitro. High-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (HPLC-Q-TOF-MS/MS) characterized 23 main components of AN. AN significantly improved cardiac function in the TAC-induced mice. Furthermore, AN considerably reduced the serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (CTn-T), and interleukin-6 (IL-6) and mitigated inflammatory cell infiltration. Post-AN treatment, TAC-induced heart size approached normal. AN decreased cardiomyocyte cross-sectional area and attenuated the upregulation of cardiac hypertrophy marker genes (ANP, BNP, and MYH7) in vivo and in vitro. Concurrently, AN alleviated collagen deposition in TAC-induced mice. AN also reduced the expression of fibrosis-related indicators (COL1A1 and COL3A1) and inhibited the activation of the transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog 3 (Smad3) pathway. Thus, AN improved TAC-induced cardiac remodeling. Moreover, AN downregulated p-dynamin-related protein (Drp1) (Ser616) expression and upregulated mitogen 2 (MFN-2) and optic atrophy 1 (OPA1) expression in vivo and in vitro, thereby restoring mitochondrial fusion and fission balance. In conclusion, AN improves cardiac remodeling by regulating mitochondrial dynamic balance, providing experimental data for the rational application of Chinese medicine prescriptions with AN as the main component in clinical practice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Myocytes, Cardiac/metabolism* ; Mice ; Rats ; Male ; Mitochondrial Dynamics/drug effects* ; Ventricular Remodeling/drug effects* ; Astragalus Plant/chemistry* ; Mice, Inbred C57BL ; Rhizome/chemistry* ; Panax notoginseng/chemistry* ; Rats, Sprague-Dawley ; Natriuretic Peptide, Brain/genetics* ; Humans ; Angiotensin II ; Astragalus propinquus

OBJECTIVE: To reveal the anti-inflammatory mechanism of Guanxin V, which is prescribed for ventricular remodeling in clinical practice. METHODS: Guanxin V-, ventricular remodeling-, and inflammation-related targets were obtained through an integrated strategy of virtual screening and systematic pharmacology, and then the shared targets were visualised with a Venn diagram. Guanxin V network and the protein-protein interaction network were drawn, and enrichment analysis was conducted. Finally, the main results obtained from the integrated strategy were validated by molecular docking and in vivo experiments. RESULTS: A total of 251, 11,425, and 15,246 Guanxin V-, ventricular remodeling-, and inflammation-related targets were acquired, respectively. Then, 211 shared targets were considered to contribute to the mechanism of ventricular remodeling treated by Guanxin V. Guanxin network and the protein-protein interaction network were drawn, and enrichment analysis showed some cardiovascular-related biological processes and signaling pathways. Molecular docking revealed that the Guanxin V-derived compounds could align with key targets. Final in vivo experiments proved that Guanxin V reverses ventricular remodeling by inhibiting inflammation. CONCLUSION Guanxin V relieves ventricular remodeling by regulating inflammation, which provides new ideas for the anti-ventricular remodeling mechanism of Guanxin V.
Humans ; Molecular Docking Simulation ; Network Pharmacology ; Ventricular Remodeling ; Inflammation/drug therapy*

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).
Humans ; ST Elevation Myocardial Infarction/therapy* ; Stroke Volume ; Ventricular Remodeling ; Prospective Studies ; Microcirculation ; Ventricular Function, Left ; Myocardial Infarction/etiology* ; Treatment Outcome ; Percutaneous Coronary Intervention/adverse effects* ; Heart Failure/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic

Heart failure with preserved ejection fraction (HFpEF) displays normal or near-normal left ventricular ejection fraction, diastolic dysfunction, cardiac hypertrophy, and poor exercise capacity. Berberine, an isoquinoline alkaloid, possesses cardiovascular benefits. Adult male mice were assigned to chow or high-fat diet with L-NAME ("two-hit" model) for 15 weeks. Diastolic function was assessed using echocardiography and noninvasive Doppler technique. Myocardial morphology, mitochondrial ultrastructure, and cardiomyocyte mechanical properties were evaluated. Proteomics analysis, autophagic flux, and intracellular Ca²⁺ were also assessed in chow and HFpEF mice. The results show exercise intolerance and cardiac diastolic dysfunction in "two-hit"-induced HFpEF model, in which unfavorable geometric changes such as increased cell size, interstitial fibrosis, and mitochondrial swelling occurred in the myocardium. Diastolic dysfunction was indicated by the elevated E value, mitral E/A ratio, and E/e' ratio, decreased e' value and maximal velocity of re-lengthening (-dL/dt), and prolonged re-lengthening in HFpEF mice. The effects of these processes were alleviated by berberine. Moreover, berberine ameliorated autophagic flux, alleviated Drp1 mitochondrial localization, mitochondrial Ca²⁺ overload and fragmentation, and promoted intracellular Ca²⁺ reuptake into sarcoplasmic reticulum by regulating phospholamban and SERCA2a. Finally, berberine alleviated diastolic dysfunction in "two-hit" diet-induced HFpEF model possibly because of the promotion of autophagic flux, inhibition of mitochondrial fragmentation, and cytosolic Ca²⁺ overload.
Male ; Mice ; Animals ; Heart Failure/drug therapy* ; Stroke Volume/physiology* ; Ventricular Function, Left/physiology* ; Berberine/therapeutic use* ; Disease Models, Animal ; Mitochondrial Dynamics ; Myocardium ; Homeostasis

Objective: To assess the clinical features and relative factors of left ventricular hypertrophy (LVH) in children with primary hypertension. Methods: In this retrospective cohort study, 430 children diagnosed with primary hypertension in Children's Hospital, Capital Institute of Pediatrics from January 2019 to September 2022 were enrolled. Their clinical data was analyzed and LVH was assessed by echocardiography. According to left ventricular geometry, these children were assigned to the LVH group and normal geometry group. General conditions, laboratory indicators and ambulatory blood pressure parameters between two groups were compared by independent sample t-test or Mann-Whitney U test. Spearman correlation coefficient was used to analyze the correlation between LVH and clinical indicators including blood pressure, biochemical and metabolic indicators. The independent risk factors of LVH were analyzed by multivariable logistic regression. The receiver operating characteristic (ROC) curve was used to explore the value of risk factors in the diagnosis of LVH. Results: Among the 430 children with primary hypertension, 342 (79.5%) were males and 88 (20.5%) females. Their age was (12.6±2.3) years, and 123 children (28.6%) of them had LVH. Body mass index (BMI) ((30.0±5.2) vs. (26.2±4.3) kg/m²), ratio of stage 2 hypertension (75.6% (93/123) vs. 59.6% (183/307)), 24-hour systolic blood pressure (24 h SBP)((131±10) vs. (128±10) mmHg,1 mmHg=0.133 kPa), daytime systolic blood pressure (SBP) ((135±11) vs. (131±11) mmHg), nighttime SBP ((128±11) vs. (123±10) mmHg), cholesterol level ((4.0±0.7) vs. (3.9±0.7) mmol/L), serum uric acid level ((447±81) vs. (426±91) μmol/L) and incidence of hyperinsulinemia (69.9% (86/123) vs.59.0% (181/307)) were significantly elevated in the LVH group compared with those in the normal geometry group (all P<0.05). There were more patients with a disease course over 5 years in the LVH group than in the normal geometry group, with a statistically significant difference (χ²=8.90,P=0.031). Spearman correlation analysis showed that BMI, 24 h SBP, daytime SBP, nighttime SBP, triglyceride, uric acid, and serum sodium level were positively correlated with LVMI (r=0.43, 0.20, 0.18, 0.18, 0.18, 0.16, and 0.12, all P<0.05). BMI, hyperinsulinemia, and cholesterol level were positively correlated with relative wall thickness (RWT) (r=0.22, 0.12, and 0.16, all P<0.05). The multivariate logistic regression analysis showed that BMI (OR=1.17, 95%CI 1.10-1.25) and 24 h SBP (OR=1.04, 95%CI 1.01-1.08) were the independent risk factors for LVH (both P<0.05). The area under the receiver operator characteristic curve, combined with BMI and 24 h SBP, was 0.72 (95%CI 0.67-0.77, P<0.05), with a sensitivity and specificity of 71.5% and 64.8%, respectively. Conclusions: BMI and 24 h SBP are the independent risk factors for LVH in children with primary hypertension, and the combination of BMI and 24 h SBP has an acceptable diagnostic value for LVH. Early monitoring of these indexes is necessary to predict preclinical cardiac damage.
Male ; Female ; Humans ; Child ; Adolescent ; Hypertension/diagnosis* ; Hypertrophy, Left Ventricular/etiology* ; Uric Acid ; Blood Pressure Monitoring, Ambulatory ; Retrospective Studies ; Blood Pressure/physiology* ; Risk Factors ; Essential Hypertension ; Hyperinsulinism ; Cholesterol

Humans ; Cardiac Resynchronization Therapy ; Cardiac Pacing, Artificial ; Heart Ventricles ; Heart Failure/therapy* ; Treatment Outcome ; Electrocardiography ; Ventricular Function, Left