付海霞
阜外华中心血管病医院 心血管内科
Myocardial infarction (MI) is an extremely severe cardiovascular disease, which ranks as the leading cause of sudden death worldwide. Studies have proved that cardiac injury following MI can cause cardiomyocyte apoptosis and myocardial fibrosis. Bilobalide (Bilo) from Ginkgo biloba leaves have been widely reported to possess excellent cardioprotective effects. However, concrete roles of Bilo in MI have not been investigated yet. We here designed both in vitro and in vivo experiments to explore the effects of Bilo on MI-induced cardiac injury and the underlying mechanisms of its action. We conducted in vitro experiments using oxygen-glucose deprivation (OGD)-treated H9c2 cells. Cell apoptosis in H9c2 cells was assessed by conducting flow cytometry assay and evaluating apoptosis-related proteins with western blotting. MI mouse model was established by performing left anterior descending artery (LAD) ligation. Cardiac function of MI mice was determined by assessing ejection fraction (EF), fractional shortening (FS), left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD). Histological changes were analyzed, infarct size and myocardial fibrosis were measured by hematoxylin and eosin (H&E) and Masson staining in cardiac tissues from the mice. The apoptosis of cardiomyocytes in MI mice was assessed by TUNEL staining. Western blotting was applied to detect the effect of Bilo on c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinases (p38 MAPK) signaling both in vitro and in vivo. Bilo inhibited OGD-induced cell apoptosis and lactate dehydrogenase (LDH) release in H9c2 cells. The protein levels of p-JNK and p-p38 were significantly downregulated by Bilo treatment. SB20358 (inhibitor of p38) and SP600125 (inhibitor of JNK) suppressed OGD-induced cell apoptosis as Bilo did. In MI mouse model, Bilo improved the cardiac function and significantly reduced the infarct size and myocardial fibrosis. Bilo inhibited MI-induced cardiomyocytes apoptosis in mice. Bilo suppressed the protein levels of p-JNK and p-p38 in cardiac tissues from MI mice. Bilo alleviated OGD-induced cell apoptosis in H9c2 cells and suppressed MI-induced cardiomyocyte apoptosis and myocardial fibrosis in mice via the inactivation of JNK/p38 MAPK signaling pathways. Thus, Bilo may be an effective anti-MI agent.
Molecular biotechnology 2024
BACKGROUND:The prognostic nutritional index (PNI) and geriatric nutritional risk index (GNRI) are well known indicators for adverse outcomes in various diseases, but there is no evidence on their association with the risk of left atrial thrombus (LAT) in patients with valvular atrial fibrillation (VAF).METHODS:A comparative cross-sectional analytical study was conducted on 433 VAF patients. Demographics, clinical characteristics and echocardiographic data were collected and analyzed. Patients were grouped by the presence of LAT detected by transesophageal echocardiography.RESULTS:LAT were identified in 142 patients (32.79%). The restricted cubic splines showed an L-shaped relationship between PNI and LAT. The dose-response curve flattened out near the horizontal line with OR = 1 at the level of 49.63, indicating the risk of LAT did not decrease if PNI was greater than 49.63. GNRI was negative with the risk of LAT and tended to be protective when greater than 106.78. The best cut-off values of PNI and GNRI calculated by receiver operating characteristics curve to predict LAT were 46.4 (area under these curve [AUC]: 0.600, 95% confidence interval [CI]:0.541-0.658, P = 0.001) and 105.7 (AUC: 0.629, 95% CI:0.574-0.684, P<0.001), respectively. Multivariable logistic regression analysis showed that PNI ≤ 46.4 (odds ratio: 2.457, 95% CI:1.333-4.526, P = 0.004) and GNRI ≤ 105.7 (odds ratio: 2.113, 95% CI:1.076-4.149, P = 0.030) were independent predictors of LAT, respectively.CONCLUSIONS:Lower nutritional indices (GNRI and PNI) were associated with increased risk for LAT in patients with VAF.
BMC cardiovascular disorders 2023
Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1) has a well-established role in myocardial infarction, yet its involvement in atrial fibrosis and atrial fibrillation (AF) has not been elucidated. As cardiac arrhythmias caused by AF are a major global health concern, we investigated whether SHP-1 modulates AF development. The degree of atrial fibrosis was examined using Masson's trichrome staining, and SHP-1 expression in the human atrium was assessed using quantitative polymerase chain reaction (qPCR), immunohistochemistry (IHC), and western blotting (WB). We also examined SHP-1 expression in cardiac tissue from an AF mouse model, as well as in angiotensin II (Ang II)-treated mouse atrial myocytes and fibroblasts. We found that SHP-1 expression was reduced with the aggravation of atrial fibrosis in clinical samples of patients with AF. SHP-1 was also downregulated in the heart tissue of AF mice and Ang II-treated myocytes and fibroblasts, compared with that in the control groups. Next, we demonstrated that SHP-1 overexpression alleviated AF severity in mice by injecting a lentiviral vector into the pericardial space. In Ang II-treated myocytes and fibroblasts, we observed excessive extracellular matrix (ECM) deposition, reactive oxygen species (ROS) generation, and transforming growth factor beta 1 (TGF-β1)/mothers against decapentaplegic homolog 2 (SMAD2) pathway activation, all of which were counteracted by the overexpression of SHP-1. Our WB data showed that STAT3 activation was inversely correlated with SHP-1 expression in samples from patients with AF, AF mice, and Ang II-treated cells. Furthermore, administration of colivelin, a STAT3 agonist, in SHP-1-overexpressing, Ang II-treated myocytes and fibroblasts resulted in higher levels of ECM deposition, ROS generation, and TGF-β1/SMAD2 activation. These findings indicate that SHP-1 regulates AF fibrosis progression by modulating STAT3 activation and is thus a potential treatment target for atrial fibrosis and AF.
Experimental biology and medicine (Maywood, N.J.) 2023
OBJECTIVE:To evaluate whether the effect of radiofrequency ablation can be improved by using sacubitril/valsartan (S/V) to control blood pressure in hypertensive patients with persistent atrial fibrillation.METHODS:A total of 63 and 67 hypertension patients with persistent atrial fibrillation were enrolled in an S/V group and ACEI/ARB group, respectively. All patients underwent radiofrequency catheter ablation (RFCA). The blood pressure of the two groups was controlled within the range of 100-140 mmHg (high pressure) and 60-90 mmHg (low pressure). The clinical outcomes of the two groups were observed after 12 months of follow-up.RESULTS:No significant differences in blood pressure were observed between the S/V and ACEI/ARB groups. In addition, the recurrence rate of atrial fibrillation between the two groups was not different. The left atrial diameter was an independent predictor of recurrence (HR = 1.063, P = 0.008). However, in the heart failure subgroup, the recurrence rate of S/V was significantly lower than that of the ACEI/ARB group (P = 0.005), and Cox regression analysis showed that the recurrence risk of atrial fibrillation of the S/V group was 0.302 lower than that of the ACEI/ARB group. NT-proBNP, LVEF, and LAD were significantly improved in hypertension patients with heart failure when comparing cases before and at the end of follow-up.CONCLUSIONS:S/V is better than ACEI/ARB in reducing the recurrence of persistent atrial fibrillation in patients with hypertension and heart failure after RFCA.
Cardiovascular drugs and therapy 2023
BACKGROUND:Inflammation has been implicated in the progressive exacerbation of valvular atrial fibrillation (VAF) and thrombogenesis. This study aimed to analyze the association of systemic inflammation as measured by six indices with left atrial thrombus (LAT) in patients with VAF.METHODS:This comparative cross-sectional analytical study included 434 patients with VAF. Logistic regression analysis was used to assess the predictive value of LAT using six inflammation indices: neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio (MLR), white blood cell-to-mean platelet volume ratio, neutrophil-to-mean platelet volume ratio, systemic immune inflammation index, and systemic inflammation response index. Receiver operating characteristic curves were plotted, and the area under these curves (AUC) were calculated to evaluate the discriminative ability of the indices.RESULTS:Transesophageal echocardiography revealed LAT in 143 (32.9%) patients. All six indices reflected a positive correlation with C-reactive protein levels. Multivariate logistic analysis revealed that these indices were independent predictors of LAT, and MLR appeared to perform best (odds ratio 12.006 [95% confidence interval (CI) 3.404-42.347]; P < 0.001; AUC 0.639 [95% CI 0.583-0.694]; P < 0.001).CONCLUSIONS:Selected inflammatory indices were significantly and independently associated with LAT among patients with VAF.
BMC cardiovascular disorders 2023
Ventricular fibrillation (VF) is a life-threatening arrhythmia that usually happens in patients with structural heart diseases. However, fever-induced ventricular fibrillation in structurally normal hearts was reported, and the four main diseases associated with these cases were Brugada syndrome, long QT syndrome, idiopathic ventricular fibrillation, and non-cardiovascular diseases. In this review, we analyzed this phenomenon and its clinical characteristics.
Frontiers in cardiovascular medicine 2023
Background:Degradation of pro-inflammatory macrophage-mediated connexin 43 (Cx43) plays an important role in post-myocardial infarction (MI) arrhythmogenesis, microRNA (miR)-155 produced by macrophages has been shown to mediate post-MI effects. We hypothesized that miR-155 inhibition attenuated MI-induced Cx43 degradation by reducing pro-inflammatory macrophage activation.Methods:MI was induced by permanent ligation of the left anterior descending coronary artery in male C57BL/6 mice. Lipopolysaccharide (LPS)-stimulated mice bone marrow-derived macrophages (BMDMs) and hypoxia-induced neonatal rat cardiomyocytes (NRCMs) were used in vitro models. qRT-PCR, Western-blot and immunofluorescence were used to analyze relevant indicators.Results:The expression levels of miR-155, interleukin-1 beta (IL-1β), and matrix metalloproteinase (MMP)7 were higher in MI mice and LPS-treated BMDMs than in the sham/control groups, treatment with a miR-155 antagomir reversed these effects. Moreover, miR-155 inhibition reduced ventricular arrhythmias incidence and improved cardiac function in MI mice. Cx43 expression was decreased in MI mice and hypoxia-exposed NRCMs, and hypoxia-induced Cx43 degradation in NRCMs was reduced by application of conditioned medium from LPS-induced BMDMs treated with the miR-155 antagomir, but increased by conditioned medium from BMDMs treated with a miR-155 agomir. Importantly, NRCMs cultured in conditioned medium from LPS-induced BMDMs transfected with small interfering RNA against IL-1β and MMP7 showed decreased hypoxia-mediated Cx43 degradation, and this effect also was diminished by BMDM treatment with the miR-155 agomir. Additionally, siRNA-mediated suppressor of cytokine signaling 1 (SOCS1) knockdown in LPS-induced BMDMs promoted Cx43 degradation in hypoxia-exposed NRCMs, and the effect was reduced by the miR-155 inhibition.Conclusions:MiR-155 inhibition attenuated post-MI Cx43 degradation by reducing macrophage-mediated IL-1β and MMP7 expression through the SOCS1/nuclear factor-κB pathway.
Cardiovascular diagnosis and therapy 2022
The novel coronavirus pandemic has led to morbidity and mortality throughout the world. Until now, it is a highly virulent contagion attacking the respiratory system in humans, especially people with chronic diseases and the elderly who are most vulnerable. A majority of afflicted are those suffering from cardiovascular and coronary diseases. In this review article, an attempt has been made to discuss and thoroughly review the mode of therapies that alleviate cardiac complications and complications due to hypercoagulation in patients infected with the SARS-CoV-2 virus. Presently a host of thrombolytic drugs are in use like Prourokinase, Retelapse, RhTNK-tPA and Urokinase. However, thrombolytic therapy, especially if given intravenously, is associated with a serious risk of intracranial haemorrhage, systemic haemorrhage, immunologic complications, hypotension and myocardial rupture. The effects of the SARS-CoV-2 virus upon the cardiovascular system and coagulation state of the body are being closely studied. In connection to the same, clinical prognosis and complications of thrombolytic therapy are being scrutinized. It is noteworthy to mention that myocardial oxygen supply/demand mismatch, direct myocardial cells injury and acute plaque rupture are the multiple mechanisms responsible for acute coronary syndrome and cardiac complications in Covid-19 infection. However, this review has limitations as data available in this context is limited, scattered and heterogenous that questions the reliability of the same. So, more multi-centric studies involving representative populations, carried out meticulously, could further assist in responding better to cardiac complications among Covid-19 patients.
Inquiry : a journal of medical care organization, provision and financing 2022
Fibrosis serves a critical role in driving atrial remodelling-mediated atrial fibrillation (AF). Abnormal levels of the transcription factor PU.1, a key regulator of fibrosis, are associated with cardiac injury and dysfunction following acute viral myocarditis. However, the role of PU.1 in atrial fibrosis and vulnerability to AF remain unclear. Here, an in vivo atrial fibrosis model was developed by the continuous infusion of C57 mice with subcutaneous Ang-II, while the in vitro model comprised atrial fibroblasts that were isolated and cultured. The expression of PU.1 was significantly up-regulated in the Ang-II-induced group compared with the sham/control group in vivo and in vitro. Moreover, protein expression along the TGF-β1/Smads pathway and the proliferation and differentiation of atrial fibroblasts induced by Ang-II were significantly higher in the Ang-II-induced group than in the sham/control group. These effects were attenuated by exposure to DB1976, a PU.1 inhibitor, both in vivo and in vitro. Importantly, in vitro treatment with small interfering RNA against Smad3 (key protein of TGF-β1/Smads signalling pathway) diminished these Ang-II-mediated effects, and the si-Smad3-mediated effects were, in turn, antagonized by the addition of a PU.1-overexpression adenoviral vector. Finally, PU.1 inhibition reduced the atrial fibrosis induced by Ang-II and attenuated vulnerability to AF, at least in part through the TGF-β1/Smads pathway. Overall, the study implicates PU.1 as a potential therapeutic target to inhibit Ang-II-induced atrial fibrosis and vulnerability to AF.
Journal of cellular and molecular medicine 2021
OBJECTIVE:Early atrial fibrillation (AF) recurrences are common and have been shown to predict AF recurrences late after AF ablation during follow-up. Neiguan point acupuncture has been recognized to be therapeutic in treating AF in clinical practice.METHODS AND RESULTS:Eighty-five patients were enrolled in succession due to persistent AF. All patients were randomized divided into control group and acupuncture group. In the control group (n = 45), amiodarone was orally taken from the first day after pulmonary vein isolation (PVI). In the acupuncture group (n = 40), patients were treated with Neiguan point acupuncture for 7 days and amiodarone was prescribed as same as the control group after PVI. The levels of inflammatory factors were analyzed before operation, 1 week after the operation and 3 months later. After 3 months, the acupuncture group had a lower rate of early recurrences than the control group (5/40 [12.5%] vs 15/45 [33.3%], P = 0.039). The inflammatory factors level in the two groups were significantly increased after ablation. However, compared with the control group, the levels of TNF-α, IL-6, CRP, TGF-β1, MMP2 in the acupuncture group significantly lower (P < 0.05). In a multivariate analysis, acupuncture was an independent factor associated with a lower rate of early recurrences during the blanking period (odds ratio, 0.17; 95% confidence interval, 0.05-0.63; P = 0.008).CONCLUSION:Neiguan point acupuncture combined with amiodarone is superior to amiodarone alone in reducing early recurrences of patients with persistent AF after PVI. The efficacy of Neiguan acupuncture therapy on the early recurrence is associated with the decreased inflammation factors.
Journal of cardiovascular electrophysiology 2019
