Role of lysosomal cathepsin B in endothelial cell injury induced by hypoxia / 中国药理学通报

Aim To investigate whether CTSB is involved in hypoxia-induced injury of cardiac microvascular endothelial cells.Methods A hypoxia-induced endothelial cell injury model was used.Cardiac microvascular endothelial cells were isolated from CTSB gene knockout mice.CTSB was overexpressed by adenovirus delivery system, and bafilomycin was used to block autophagy.ELISA was used to detect the release of inflammatory factors.Tunel staining was used to detect the number of cell apoptosis.caspase-3 kit was used to detect the activity of cell caspase-3.Cells were infected with LC3-GFP-mCherry double-labeled adenovirus todetect cell autophagy flow.Results CTSB gene knockout could significantly aggravate the inflammation and apoptosis of endothelial cells induced by hypoxia, and increased autophagy.Overexpression of CTSB reduced the inflammation and apoptosis of endothelial cells induced by hypoxia, and increased autophagy.But bafilomycin treatment could significantly offset the inhibitory effect of CTSB overexpression on cell inflammation and apoptosis and the protective effect on cell autophagy.Conclusions CTSB knockout aggravates inflammation and apoptosis induced by hypoxia in endothelial cells; while the overexpression of CTSB ameliorates endothelial cell injury induced by hypoxia.CTSB maintains normal autophagy degradation in endothelial cells.BAF blocks the protective effect of CTSB on endothelial cells by inhibiting autophagy degradation.

Segmentation method of myocardial perfusion bull-eye for the degree of loss of cardiac ischemia / 生物医学工程学杂志

As one of the non-invasive imaging techniques, myocardial perfusion imaging provides a basis for the diagnosis of myocardial ischemia in coronary heart disease. Aiming at the bull-eye image in myocardial perfusion imaging, this paper proposed a branching structure, which included multi-layer transposed convolution up-sampling concatenate module and four-channel weighted channels attention module, and the output results of the branch structure were fused with the output results of trunk U-Net, to achieve accurate segmentation of the cardiac ischemia missing degree in myocardial perfusion bull-eye image. The experimental results show that the multi-layer transposed convolution up-sampling concatenate module realizes the fusion of different depth feature maps, and effectively reduces the interference of the severe sparse degree which is similar to the missing degree on the segmentation. Four-channel weighted attention module can further improve the ability to distinguish between the two similar degrees and the ability to learn edge details of the targets, and retain more abundant edge details features. The experimental data came from Tianjin Medical University General Hospital, Tianjin TEDA Hospital, Tianjin First Central Hospital and Third Central Hospital. The Jaccard scores in the self-built dataset was 5.00% higher than that of U-Net. The model presented in this paper is superior to other optimized models based on U-Net, and the subjective evaluation meets the accuracy requirements for clinical diagnosis.

The role and molecular mechanisms of long noncoding RNAs in cardiac diseases / 药学学报

Long noncoding RNAs (lncRNAs) are a class of RNAs that are more than 200 nucleotides in length with no protein coding property. LncRNAs are involved in almost every cellular process through multiple mechanisms. LncRNAs can directly bind to molecules in cells such as proteins, RNA, and DNA, to regulate cellular functions by influencing processes including transcription, translation, and molecular transporting. Recent researches showed lncRNAs are key regulators of serious cardiac diseases, especially in development and progression of cardiac ischemia, arrhythmia, cardiac fibrosis, and heart failure. This article mainly summarizes the function and mechanism of lncRNAs in cardiac diseases and gives reasonable prospect of lncRNAs in the future.

Cross Talk between Oxidative Stress, PPAR- γ and RAS System in Diabetic Rat Heart Exposed to Ischemia / Reperfusion Injury.

The present study aimed at clarifying the cross talk between peroxisome proliferator-activated receptor-gamma (PPAR- γ), cardiac reactive Oxygen species (ROS) and Renin-Angiotensin System (RAS). Methods: A total of 90 male albino rats were used. The rats were divided into: Group 1: Control group, Group 2: Type 2 diabetic rats, Group 3: PPARγ agonist protected type 2 diabetic rats. Group 4: Antioxidant protected type2 diabetic rats, Group 5: Metformin treated type 2 diabetic rats. Blood samples were collected for measurement of FBS and fasting insulin. Half the number of each group was sacrificed and the heart excised and perfused, from the rest of the group small piece from the heart was taken for estimation of malondialdehyde (MDA), Angiotensin 2 Receptor (AT2R) and Angiotensin Converting Enzyme 2 (ACE2) gene expression. Results: Treatment with pioglitazone and Vitamin E significantly lowered blood glucose, insulin levels and Homeostasis Model Assessment Insulin Resistance (HOMA IR). However, values did not return to control values. Pioglitazone and Vitamin E improved myocardial performance and percentage recovery following ischemia reperfusion. The cardioprotective effect was more pronounced in the pioglitazone group. This positively correlated with decreased MDA levels and increased AT2R and ACE2 expression in cardiac tissue. Conclusion: Pioglitazone and Vitamin E in type 2 DM significantly offered cardioprotection through improving the diabetic condition and / or decreasing MDA levels.

Adeno-associated Viral Vector Mediated and Cardiac-specific Delivery of CD151 Gene in Ischemic Rat Hearts / 华中科技大学学报（医学）（英德文版）

Our previous studies demonstrated that CD151 gene promoted neovascularization in ischemic heart model.To improve the delivery efficacy and target specificity of CD1 51 gene to ischemic heart,we generated an adeno-associated virus (AAV) vector in which CD151 expression was controlled by the myosin light chain (MLC-2v) promoter to achieve the cardiac-specific expression of CD 151 gene in ischemic myocardium and to limit unwanted CD151 expression in extracardiac organs.The function of this vector was examined in rat ischemic myocardium model.The protein expression of CD151 in the ischemic myocardium areas,liver and kidney was confirmed by using Western blot,while the microvessels within ischemic myocardium areas were detected by using immunohistochemistry.The results showed that MLC-2v significantly enhanced the expression of CD151 in ischemic myocardium,but attenuated its expression in other organs.The forced CD151 expression could increase the number of microvessels in the ischemic myocardium.This study demonstrates the AAV-mediated and MLC-2v regulated CD151 gene is highly expressed in the ischemic myocardium and cardiac-specific delivery that is more efficiently targets CD151 to the ischemia myocardium after myocardial infarction.

La frecuencia cardiaca y su intervención en el manejo de la enfermedad isquémica cardiaca. Un nuevo abordaje y alternativa / Heart rate and its intervention in ischemic heart disease. A new approach and alternative

Desde hace mucho tiempo se sabe que en las diferentes escalas zoológicas la frecuencia cardiaca es un factor que determina la esperanza de vida en años. En la especie humana parece suceder algo similar. En un reciente estudio (BEAUTIFUL), en enfermos con falla cardiaca y enfermedad coronaria, los pacientes con una frecuencia cardiaca > 70 lpm obtuvieron un beneficio significativo en eventos coronarios, hospitalización por infarto del miocardio y revascularización coronaria, al reducirla con un nuevo medicamento que actúa exclusivamente en la corriente If del nodo sinusal, reduciéndola sin componente hemodinámico asociado (esto es, no efecto inotrópico negativo). La enfermedad isquémica cardiaca se ha visto como un disbalance entre la oferta y la demanda de oxígeno en el miocardio. Por tal motivo, los medicamentos que disminuyen su consumo (betabloqueadores y algunos calcioantagonistas), a través del efecto inotrópico negativo, se han convertido en el pilar fundamental para el manejo de este proceso. Sin embargo, el efecto betabloqueador tiene un sobrecosto el cual es el efecto vasoconstrictor mediado por el efecto alfa que se libera al bloquear los receptores beta. De ahí que los betabloqueadores con efecto vasodilatador -carvedilol, nebivolol- no tengan esta desventaja. Recientemente, surgió una nueva clase terapéutica que puede coadyuvar en el manejo de enfermos coronarios, al disminuir de manera selectiva la frecuencia cardiaca y prolongar el tiempo de llenado diastólico, mejorando la perfusión miocárdica sobre todo en la zona más vulnerable: el sub-endocardio. El primer medicamento de esta clase es la ivabradina. Se hace una revisión sobre el papel de la frecuencia cardiaca en el sistema cardiovascular, la corriente If, la fisiología de la enfermedad isquémica cardiaca y los beneficios de la ivabradina al disminuir exclusivamente la frecuencia cardiaca con su impacto adicional sobre la pared vascular y más específicamente en la hemodinámica de la placa aterosclerótica.

We have known for many years that in the different zoological scales the heart rate is a determinant of life expectancy in years. It seems that something similar occurs in the human species. In a recent study (BEAUTIFUL), performed in patients with heart failure and coronary heart disease, patients with heart rate higher or equal to 70 beats per minute had a significant benefit in coronary events, hospitalization for cardiac infarct and coronary revascularization, by reducing it with a new drug that acts exclusively in the sinus node If current, without any hemodynamic associated component (this is, no inotropic negative effect).Ischemic heart disease has been seen as an imbalance between oxygen supply and demand in the myocardium. Therefore, medications that decrease its consumption (betablockers and some calcium antagonists) have become the mainstay for the management of this process, due to its negative inotropic effect. Nevertheless, betablocker effect has an extra cost that is the vasoconstrictor effect, mediated by the alfa effect that is liberated when blocking the beta receptors. For that reason, betablockers with vasodilator effect-carvediol, nebivolol- do not have this disadvantage. Recently, a new therapeutic class that may help in coronary patients management emerged, by selectively decreasing the heart rate and prolonging diastolic filling time, improving myocardial perfusion especially in the most vulnerable zone: the subendocardium. The first specific heart rate-lowering agent is ivabradine. A review of the heart rate role on the cardiovascular system, the If current, ischemic heart disease physiology, and ivabradine benefits when exclusively decreasing the heart rate with its additional impact on the vascular wall and more specifically in the atheroesclerotic plaque hemodynamics, is made.

Reduction of Muscarinic K+ Channel Activity by Transferrin in Ischemic Rat Atrial Myocytes

It has been demonstrated that an unidentified cytosolic factor (s) reduces K (ACh) channel function. Therefore, this study attempted to elucidate the cytosolic factor. Fresh cytosol isolated from normal heart (FC) depressed the K (ACh) channel activity, but cytosol isolated from the ischemic hearts (IC) did not modulate the channel function. Electrophorectic analysis revealed that a protein of ~80 kDa was markedly reduced or even lost in IC. By using peptide sequencing analysis and Western blot, this 80 kDa protein was identified as transferrin (receptor-mediated Fe3+ transporter, 76 kDa). Direct application of transferrin (100 nM) to the cytoplasmic side of inside-out patches decreased the open probability (Po, 12.7+/-6.4%, n=4) without change in mean open time (tau o, 98.5+/-1.3%, n=4). However, the equimolar apotransferrin, which is free of Fe3+, had no effect on the channel activity (N*Po, 129.1+/-13.5%, n=3). Directly applied Fe3+ (100 nM) showed results similar to those of transferrin (N*Po: 21.1+/-3.9%, n=5). However Fe2+ failed to reduce the channel function (N*Po, 106.3+/-26.8%, n=5). Interestingly, trivalent cation La (3+) inhibited N*Po of the channel (6.1+/-3.0%, n=3). Taken together, these results suggest that Fe3+ bound to transferrin can modulate the KACh channel function by its electrical property as a polyvalent cation.

Two Cases of Transient Cardiac Attacks Related to Steroid Pulse Therapy

No abstract available.

Limb ischemia preconditions myocardium:the role of nitric oxide and neurogenic pathway / 中国药理学通报

Aim To investigate a possible role for nitric oxide and neurogenic pathway in the protective effect of the limb preconditioning on the ischemic-reperfusion myocardium.Methods 64 Wistar rats were randomly divided into one of the four experimental groups.In Group Ⅰ,the rats underwent 30 min occlusion of the left anterior descending coronary artery,and 120 min reperfusion.In Group PL,the rats underwent four cycles of 5 min occlusion and reperfusion of both hind limbs using a tourniquet before the experiment was continued as in Group Ⅰ.In Group PL-N and Group PL-H,rats were administered with L-Nitro-Arginine Methyl Ester(L-NAME)10 mg?kg-1 or hexamethonium chloride 20 mg?kg-1,intravenously,20 min before IPC.Infarct size,as a percentage of the area at risk,was determined by triphenyltetrazolium chloride staining.And other 8 rats in each group,at the end of the experiment,all rats were killed and myocardium were stored in liquid nitrogen for the measurement of NO,NOS,iNOS and iNOS mRNA.Results The myocardial infarct size(IS)was decreased significantly in Group PL and Group PL-H compared with Group Ⅰ(P

Acute Cardiac Ischemia in Young Adults: Characteristics and Risk Factors

PURPOSE: Acute cardiac ischemia under the age of 45 years is uncommon. This study was to evaluate the prevalence of various risk factors, the angiographic characteristics, and the prognosis in young patients with acute cardiac ischemia compared with that in older patients. METHODS: A review was retrospectively done of 554 patients with acute cardiac ischemia from January 2002 to December 2002. The patients were divided into two groups: patients under 45 years old (75 patients) and patients over 45 years old (479 patients). The clinical features which were compared between the two groups were demographic features, risk factors (cigarette smoking, history of hypertension and diabetes, hypercholesterolemia, hypertriglyceridemia, and family history of ischemic cardiac disease), coronary angiographic findings, and prognosis. RESULTS: The incidence of acute cardiac ischemia in patients under 45 years old was 13.5% (75/554). Three clinical risk factors, a history of cigarette smoking, a positive family history coronary artery disease, and hypertriglyceridemia, were significantly more prevalent in the young patients. Angiographically, normal or minimal coronary obstructions were more frequently found in the young patients, and significant coronary obstructions were more frequently found in the older patients. However the incidences of single-vessel disease and multi-vessel disease between young patients and older patients were not different. Young patients with acute cardiac ischemia do not have a more favorable prognosis than older patients. CONCLUSION: Acute cardiac ischemia is found in young patients with less extensive disease, but young patients do not have a more favorable prognosis than older patients.