Jing P, Zhou LH, Chen YX
… +6 more, Gu LF, Du C, Yang TT, Chen SX, Wang H, Wang LS
Zhonghua Xin Xue Guan Bing Za Zhi
· 2025 Dec · PMID 41402105
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To investigate the biological role and molecular mechanism of checkpoint kinase 1 (CHK1) in delaying cardiac aging in mice. In vitro, a senescence model of H9C2 cells (a cardiomyocyte line) was induced using HO. A contr...To investigate the biological role and molecular mechanism of checkpoint kinase 1 (CHK1) in delaying cardiac aging in mice. In vitro, a senescence model of H9C2 cells (a cardiomyocyte line) was induced using HO. A control group (without HO treatment) and three HO-treated groups (at concentrations of 10, 30, and 50 μmol/L) were set up. The CCK-8 assay was used to evaluate the proliferative activity of cells in each group; Western blot analysis was employed to detect the expression level of CHK1; and quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to determine the messenger RNA (mRNA) expression levels of P16 and interleukin-1β (IL-1β). In vivo, C57BL/6 wild-type mice aged 2 months (=15) and 24 months (=40), as well as myocardial-specific CHK1-overexpressing (CHK1-TG) mice aged 2 months (=15) and 24 months (=40), were selected. The mice were divided into four groups based on age and genotype: 2-month-old wild-type (WT-2M), 24-month-old wild-type (WT-24M), 2-month-old CHK1-TG (CHK1-TG-2M), and 24-month-old CHK1-TG (CHK1-TG-24M). Echocardiography was used to evaluate cardiac function of mice in the WT-24M and CHK1-TG-24M groups. Western blot analysis was conducted to measure the protein expression levels of CHK1, total Ras-related protein 1 (Rap1), NADPH oxidase 4 (Nox4), and Rap1-guanosine triphosphate (Rap1-GTP, the active form of Rap1) in the cardiac tissue of mice in each group. qRT-PCR was used to detect the messenger RNA (mRNA) expression levels of CHK1, collagen type Ⅰ (Coll1), matrix metalloproteinase-2 (Mmp2), alpha-smooth muscle actin (α-SMA), P53, P21, P16, thioredoxin 1 (Trx1), thioredoxin reductase (TrxR), glutathione recluctase (GR), Rap1, and Nox4. Immunofluorescence staining was employed to determine the protein expression levels of P53, P21, and P16, as well as the proportion of histone H2AX phosphorylation-positive cells. Dihydroethidium (DHE) staining was used to detect the relative intensity of DHE. Wheat germ agglutinin staining, HE staining, Masson staining and Sirius red staining were applied to measure the cross-sectional area of cardiomyocytes, cardiac morphology, and myocardial fibrosis area. Mice in the WT-24M and CHK1-TG-24M groups were intraperitoneally injected with the Rap1 activity inhibitor GGTI298 (25 μmol/kg). After injection, the oxidative stress damage in the cardiac tissue of the mice was detected, along with the mRNA expression levels of fibrosis-related indicators (Coll1, Mmp2, and α-SMA) and cell cycle inhibitory proteins (P16, P21, and P53). A concentration of 30 μmol/L was determined as the optimal concentration for establishing an HO-induced senescence model of myocardial cells in vitro. The expression level of CHK1 in H9C2 cells of the 30 μmol/L HO group was lower than that in the control group (<0.05). Echocardiographic examination showed that the left ventricular ejection fraction ((61.08±1.13)% vs. (52.55±2.02)%) and fractional shortening ((31.80±1.27)% vs. (25.18±1.59)%) of mice in the CHK1-TG-24M group were higher than those in the WT-24M group (both <0.05). qRT-PCR and Western blot analysis revealed that, compared with the WT-24M group, mice in CHK1-TG-24M group had higher expression levels of CHK1 and its mRNA, lower expression levels of Nox4 and its mRNA, and higher expression level of Rap1-guanosine triphosphate (Rap1-GTP) (all <0.05). However, there were no statistically significant differences in the total expression level of Rap1 and its mRNA between the two groups (both >0.05). In addition, the mRNA expression levels of Coll1, Mmp2, and α-SMA in myocardial tissue of mice in the CHK1-TG-24M group were lower than those in the WT-24M group (all <0.05). Immunofluorescence staining results showed that the expression levels of P53, P21, and P16 proteins, as well as the proportion of phosphorylated histone H2AX-positive cells in myocardial tissue of mice in the WT-24M group were higher than those in the CHK1-TG-24M group (all <0.05). qRT-PCR further confirmed that the mRNA expression levels of the above-mentioned proteins in cardiac tissue of mice in the WT-24M group were higher than those in the CHK1-TG-24M group (all <0.05). DHE staining results indicated that the relative intensity of DHE in cardiac tissue of mice in the CHK1-TG-24M group was lower than that in the WT-24M group (<0.05). Meanwhile, the left ventricular internal diameter, cross-sectional area of cardiomyocytes, and myocardial fibrosis area of mice in the CHK1-TG-24M group were all smaller than those in the WT-24M group (all <0.05). Furthermore, the degree of DNA damage in cardiac tissue as well as the mRNA levels of fibrosis-related indicators (Coll1, Mmp2, and α-SMA) and cell cycle inhibitory proteins (P53, P21, P16) in mice of the WT-24M+GGTI298 group were higher than those in the WT-24M group and the CHK1-TG-24M+GGTI298 group (all <0.05). CHK1 alleviates oxidative stress-induced damage in mouse cardiomyocytes by activating the Rap1/Nox4 signaling pathway, thereby delaying cardiac aging in mice.
Zhao XM, Shen YX, Gao CY
… +8 more, Li MW, Wu HY, Yang W, Zhang L, Liu M, Xing F, Du TM, Liu L
Zhonghua Xin Xue Guan Bing Za Zhi
· 2025 Dec · PMID 41402104
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Investigation of the relationship between variant angina pectoris syncope and coronary artery spastic targeted location, arrhythmias, and coronary artery stenostic lesion. This study combined retrospective and prospecti...Investigation of the relationship between variant angina pectoris syncope and coronary artery spastic targeted location, arrhythmias, and coronary artery stenostic lesion. This study combined retrospective and prospective registry approaches. Data were sourced from the case database of Henan province "Multicenter Clinical Observation Study of Variant Angina Pectoris". A total of 507 patients with variant angina pectoris who had complete records from June 1980 to December 2022 were consecutively enrolled. Select patients among them who experienced syncope, and analyze the target vessel sites of coronary artery spasm, arrhythmias during variant angina pectoris attacks, and the degree of stenosis in coronary artery lesions. Among 507 variant angina pectoris patients, 88 experienced syncope. Age was (53.9±9.7) years and 66 patients (75.0%) were male. Forty patients (45.5%, 40/88) were aged 50-59 years. The incidence of syncope in variant angina pectoris caused by left anterior descending artery (LAD) spasm, right coronary artery (RCA) spasm, and multivessel coronary artery spasm was 7.4% (15/202), 22.7% (42/185), and 23.6% (25/106), respectively. The latter two were significantly higher than those in the LAD group (<0.05). Among 77 patients with variant angina pectoris syncope, definitive electrocardiogram recordings were available during syncope episodes. All patients exhibited arrhythmias during syncope: 34 cases involved tachyarrhythmias and 43 cases involved bradyarrhythmias. The incidence of rapid arrhythmias in patients with LAD, RCA, and multi-vessel spasm syncope was 72.7% (8/11), 24.3% (9/37), and 54.2% (13/24), respectively, with <0.05 for the first two. Bradyarrhythmias occurred in 27.3% (3/11) of LAD, 75.7% (28/37) of RCA, and 45.8% (11/24) of multivessel coronary artery spasm syncope cases, with the first two showing <0.05. Coronary angiography analysis of 56 syncope patients revealed target vessel locations and stenosis severity: 12 patients had LAD lesions and 41 had RCA lesions, stenosis ≥50% occurred in 66.7% (8/12) and 43.9% (18/41) of these lesions, respectively (>0.05). Variant angina pectoris syncope predominantly affects middle-aged males. Bradyarrhythmias triggered by RCA spasm are a common cause, while the incidence of syncope shows no significant correlation with the degree of coronary artery stenostic lesion, whether in the LAD or the RCA.
Yuan CZ, Ze F, Wu CC
… +5 more, Duan JB, Zhou X, Yang DD, Li D, Li XB
Zhonghua Xin Xue Guan Bing Za Zhi
· 2025 Dec · PMID 41402103
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To evaluate the incidence and frequency of inappropriate shocks caused by defibrillation lead failure in patients with implantable cardioverter-defibrillators (ICD), and to explore methods for reducing the incidence and...To evaluate the incidence and frequency of inappropriate shocks caused by defibrillation lead failure in patients with implantable cardioverter-defibrillators (ICD), and to explore methods for reducing the incidence and frequency of such inappropriate shocks. This was a single-center retrospective study involving patients treated for defibrillation lead failures at Peking University People's Hospital between March 2015 and May 2024. Patients were divided into an alarm function group and a non-alarm function group based on whether their ICDs were equipped with lead alarm functions. Clinical data, lead data, and the incidence and frequency of inappropriate shocks were collected and compared between the two groups. A multivariate logistic regression model was used to analyze factors influencing the incidence and frequency of inappropriate ICD shocks. Kaplan-Meier survival curves were plotted to compare the trends in the incidence and frequency of inappropriate shocks over time since ICD implantation between the two groups. A total of 59 patients were enrolled, with a age of (56.7±15.2) years, including 42 males (71%). The lifespan of the failed leads in the entire cohort was 64.0 (36.0, 96.0) months. There were 26 patients in the alarm function group and 33 in the non-alarm function group. The most common manifestations of lead failure were oversensing (85%, 50/59) and abnormal pacing impedance (42%, 25/59). A total of 33 patients (56%, 33/59) experienced inappropriate shock therapy, with an average of 27.3 shocks per patient. The frequency of inappropriate ICD shocks in the non-alarm function group was higher than that in the alarm function group (25.0 (10.0, 60.0) times/year vs. 5.0 (2.8, 7.8) times/year, =0.001). Multivariate logistic regression analysis showed that oversensing (=2.057, 95% 1.125-6.763, =0.019) was an influencing factor for incidence of inappropriate shocks, while the lead alert function (=0.062, 95% 0.005-0.719, =0.001) was a factor influencing the frequency of inappropriate shocks. Kaplan-Meier survival analysis revealed that the incidence and frequency of inappropriate shocks increased with the duration of ICD implantation in both groups, but the differences were not statistically significant (incidence: log-rank =0.908; frequency: log-rank =0.767). The lead alert function can reduce the frequency of inappropriate shocks caused by lead failure.
Wei H, Bao W, Hu XQ
… +6 more, Bao HM, Ge LQ, Li F, Zhang CQ, Wang ZR, Li CZ
Zhonghua Xin Xue Guan Bing Za Zhi
· 2025 Dec · PMID 41402102
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To investigate the impact of imaging anatomical features on the prognosis of middle-aged and elderly patients with anomalous coronary artery originating from the opposite sinus (ACAOS). This retrospective cohort study e...To investigate the impact of imaging anatomical features on the prognosis of middle-aged and elderly patients with anomalous coronary artery originating from the opposite sinus (ACAOS). This retrospective cohort study enrolled patients aged ≥45 years who were diagnosed with ACAOS by coronary computed tomography angiography (CTA) at the Affiliated Hospital of Xuzhou Medical University between January 1, 2011, and December 31, 2018. Baseline clinical data and coronary CTA images were collected. Anatomic imaging features were extracted, including ACAOS subtype, course of the anomalous vessel, and ostial angle. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of acute myocardial infarction, cardiac death, and coronary revascularization. The Maxstat method was used to determine the cut-off values of specific anatomical features for predicting MACE risk. Cox proportional hazards models were employed to analyze the impact of these imaging features on MACE in middle-aged and elderly ACAOS patients. A total of 203 patients were enrolled, aged (60.0(51.0, 66.0)) years, including 119 (58.6%) males. Over a follow-up of (98.2±30.9) months, 39 patients experienced MACE. Maxstat identified an optimal cut-off value of 34.3° for the ostial angle of the anomalous vessel. Multivariable Cox proportional hazards regression analysis revealed that the following factors were independent risk factors for MACE: left-sided ACAOS subtype (=4.35, 95% 2.17-8.73, <0.001), an interarterial course between the aorta and pulmonary artery (=3.21, 95% 1.23-8.37, =0.017), an anomalous vessel ostial angle <34.3° (=2.62, 95% 1.18-5.77, =0.017), and concomitant coronary artery disease (=2.92, 95% 1.49-5.73, =0.002). In middle-aged and elderly patients with ACAOS, the imaging anatomical features of a left-sided ACAOS subtype, an interarterial course, and an ostial angle <34.3° are independent risk factors for MACE.
Zhonghua Xin Xue Guan Bing Za Zhi
· 2025 Dec · PMID 41402101
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Investigate key genes influencing vascular calcification through bioinformatics analysis and experimental validation. Three vascular calcification datasets (GSE159832, GSE229679 and GSE37558) were obtained from the Gene...Investigate key genes influencing vascular calcification through bioinformatics analysis and experimental validation. Three vascular calcification datasets (GSE159832, GSE229679 and GSE37558) were obtained from the Gene Expression Omnibus database. Subsequently, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and conventional gene set enrichment analysis (GSEA) were performed on the common differential expressed genes(DEGs). For in vitro validation, a vascular smooth muscle cell calcification model was established by stimulating mouse primary vascular smooth muscle cells with high phosphate and calcium chloride (Pi+CaCl). Cells were divided into a control group and a Pi+CaCl group. To investigate the role of TK1, cells were transfected with TK1-targeting siRNA (siTK1) or control siRNA (siControl) prior to Pi+CaCl stimulation, creating siControl+Pi+CaCl and siTK1+Pi+CaCl groups. The association between key DEGs and vascular calcification was assessed at the protein and mRNA levels using Western blot and quantitative real-time PCR, respectively. Changes in the phosphorylation of the downstream effector, AKT (p-AKT/AKT), were also measured. A total of 2275, 449, and 381 DEGs were identified from the three vascular calcification datasets (GSE159832, GSE229679, and GSE37558), respectively. Two common DEGs-phosphoserine aminotransferase 1 and thymidine kinase 1 (TK1)-were identified across all datasets. GO enrichment analysis revealed that TK1 was significantly enriched in pathways related to ribosome biogenesis, assembly, and rRNA processing and maturation. GSEA-KEGG analysis indicated significant enrichment in the PI3K-AKT signaling pathway, pathways in cancer, neurodegenerative diseases, cytoskeleton, and smooth muscle contraction. Conventional GSEA of TK1 further confirmed significant enrichment in pathways including dynein, epithelial tight junctions, axon guidance, and vascular smooth muscle contraction pathways. At the experimental level, both protein and mRNA expression of TK1, along with the p-AKT/AKT ratio, were significantly lower in the Pi+CaCl group compared to the control group (all <0.05). Furthermore, compared to the siControl+Pi+CaCl group, the siTK1+Pi+CaCl group exhibited decreased expression of differentiation markers, increased expression of calcification markers, and a further reduced p-AKT/AKT ratio (all <0.05). Integrated bioinformatics and cellular validation demonstrate a correlation between TK1 expression and vascular calcification, suggesting a potential protective role for TK1 in this pathological process.
Xie LH, Guan CD, Sun ZW
… +13 more, Qian J, Wu F, Cui JG, Huang YF, Chen J, Hu FH, Zhao J, Yang YJ, Qiao SB, Dou KF, Yang WX, Wu YJ, Song L
Zhonghua Xin Xue Guan Bing Za Zhi
· 2025 Dec · PMID 41402100
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Investigate the impact of calcification on the long-term outcomes of patients with coronary chronic total occlusion (CTO) after percutaneous coronary intervention (PCI). A retrospective cohort study was conducted. Patie...Investigate the impact of calcification on the long-term outcomes of patients with coronary chronic total occlusion (CTO) after percutaneous coronary intervention (PCI). A retrospective cohort study was conducted. Patients who underwent PCI and had at least one CTO lesion at Fuwai Hospital between January 2010 and December 2013 were consecutively enrolled. Calcification was evaluated by coronary angiography, and patients were divided into two groups: moderate/severe calcification group and non/mild calcification group. Clinical follow-up was completed up to 5 years. Incidence of PCI-related complications and immediate procedural outcomes were compared between two groups, and the primary endpoint was the target lesion failure (TLF) at 5 years after PCI. Clinical follow-up endpoint events were analyzed using Kaplan-Meier survival analysis with log-rank test, and Cox multivariate regression model was used to evaluate the relationship between calcification and TLF. The study included 2 659 CTO patients with an age of (57.2±10.5) years, of whom 442 (16.6%) were female, and among whom 13.5% (360/2 659) had moderate/severe calcification. Compared with the non/mild calcification group, the moderate/severe calcification group had a higher incidence of PCI-related complications (43.2% (156/361) vs. 32.5% (772/2 374), <0.001) and procedural failure (34.3% (124/361) vs. 24.3% (577/2 374), <0.001). Additionally, the moderate/severe calcification group showed a higher risk of the primary endpoint event (TLF) during the 5-year follow-up (19.8% vs. 15.3%, log-rank =0.028). Higher incidence of cardiac death was observed in moderate/severe calcification group (5.7% vs. 2.7%, log-rank =0.003). Cox multivariate regression analysis revealed that moderate/severe calcified plaques remained an independent risk factor for 5-year TLF after CTO-PCI (=1.34, 95%: 1.01-1.79, =0.043). Compared with CTO patients with non/mild calcification, those with moderate/severe calcification have higher procedural failure and complication rates, as well as poorer long-term prognosis, mainly due to an increase in cardiac death.
Li JY, Luo JY, Xu ZM
… +3 more, Xue Y, Li Y, Han YL
Zhonghua Xin Xue Guan Bing Za Zhi
· 2025 Dec · PMID 41402099
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Publisher ↗
Investigate the clinical characteristics of patients with coronary artery disease (CAD) and moderate-to-severe coronary calcification lesions confirmed by intravascular ultrasound (IVUS), and to compare the prevalence of...Investigate the clinical characteristics of patients with coronary artery disease (CAD) and moderate-to-severe coronary calcification lesions confirmed by intravascular ultrasound (IVUS), and to compare the prevalence of moderate-to-severe calcification lesions among different clusters of patients with CAD. This cross-sectional study enrolled patients with coronary artery disease who underwent coronary angiography and IVUS at the General Hospital of Northern Theater Command from June 2016 to June 2023. Patients with mild calcification were excluded, and the remaining cohort was divided into moderate-to-severe calcification and non-calcification groups. The least absolute and selective operator logistic regression was used to identify baseline variables associated with mederate-to-severe calcification. Hierarchical cluster analysis was used to identify similarities in clinical baseline data among patients, and the prevalence of moderate-to-severe coronary calcification was compared across different clusters of patients with CAD. A total of 1 406 patients with CAD were enrolled (age (60.7±10.0) years; 963 males (68.5%)). A total of 563 patients were assigned in the moderate-to-severe calcification group and 843 patients were assigned in the non-calcification group. The least absolute and selective operator logistic regression identified 23 baseline variables associated with moderate-to-severe coronary artery calcification. Hierarchical cluster analysis based on these 23 variables divided all patients into Cluster 1 (500 cases) and Cluster 2 (906 cases). Patients in Cluster 1 were characterized by high age, high body mass index, high diastolic blood pressure, elevated mean arterial pressure, history of hypertension, history of diabetes, low endogenous creatinine clearance, high fasting blood glucose, low high-density lipoprotein cholesterol (HDL-C), high lipoprotein(a), high alkaline phosphatase, high glycated hemoglobin, low serum albumin, high triglycerides/HDL-C ratio, high HbA1c/HDL-C ratio, and high triglyceride glucose index. Cluster 1 (49.6%, 248/500) exhibited a significantly higher prevalence of moderate-to-severe coronary artery calcification compared to Cluster 2 (34.8%, 315/906, =0.002). Patients with moderate-to-severe coronary artery calcification exhibited clinical heterogeneity compared to those without calcification. A subgroup characterized by high age, elevated body mass index, high diastolic blood pressure, elevated mean arterial pressure, history of hypertension, history of diabetes, low endogenous creatinine clearance, and high fasting blood glucose levels demonstrated a higher prevalence of moderate-to-severe coronary artery calcification.
Chinese Society of Rare Diseases, Chinese Medical Association, Chinese Society of Cardiology, Chinese Medical Association, Editorial Board of Chinese Journal of Cardiology
Zhonghua Xin Xue Guan Bing Za Zhi
· 2025 Dec · PMID 41402096
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