4D bioprinting technology and its application in cardiovascular tissue engineering / 生物工程学报

3D bioprinting technology is a rapidly developing technique that employs bioinks containing biological materials and living cells to construct biomedical products. However, 3D-printed tissues are static, while human tissues are in real-time dynamic states that can change in morphology and performance. To improve the compatibility between in vitro and in vivo environments, an in vitro tissue engineering technique that simulates this dynamic process is required. The concept of 4D printing, which combines "3D printing + time" provides a new approach to achieving this complex technique. 4D printing involves applying one or more smart materials that respond to stimuli, enabling them to change their shape, performance, and function under the corresponding stimulus to meet various needs. This article focuses on the latest research progress and potential application areas of 4D printing technology in the cardiovascular system, providing a theoretical and practical reference for the development of this technology.

Ferroptosis is essential for diabetic cardiomyopathy and is prevented by sulforaphane via AMPK/NRF2 pathways

Herein, we define the role of ferroptosis in the pathogenesis of diabetic cardiomyopathy (DCM) by examining the expression of key regulators of ferroptosis in mice with DCM and a new ex vivo DCM model. Advanced glycation end-products (AGEs), an important pathogenic factor of DCM, were found to induce ferroptosis in engineered cardiac tissues (ECTs), as reflected through increased levels of Ptgs2 and lipid peroxides and decreased ferritin and SLC7A11 levels. Typical morphological changes of ferroptosis in cardiomyocytes were observed using transmission electron microscopy. Inhibition of ferroptosis with ferrostatin-1 and deferoxamine prevented AGE-induced ECT remodeling and dysfunction. Ferroptosis was also evidenced in the heart of type 2 diabetic mice with DCM. Inhibition of ferroptosis by liproxstatin-1 prevented the development of diastolic dysfunction at 3 months after the onset of diabetes. Nuclear factor erythroid 2-related factor 2 (NRF2) activated by sulforaphane inhibited cardiac cell ferroptosis in both AGE-treated ECTs and hearts of DCM mice by upregulating ferritin and SLC7A11 levels. The protective effect of sulforaphane on ferroptosis was AMP-activated protein kinase (AMPK)-dependent. These findings suggest that ferroptosis plays an essential role in the pathogenesis of DCM; sulforaphane prevents ferroptosis and associated pathogenesis via AMPK-mediated NRF2 activation. This suggests a feasible therapeutic approach with sulforaphane to clinically prevent ferroptosis and DCM.

Cardiac Fibrosis in right Atrial tissue is not different in male Pasifika and Pākehā Cardiac surgery patients in Aotearoa

@#Cardiovascular disease (CVD) is the leading cause of death worldwide and in New Zealand. However, a significant inequality in the burden of CVD amongst different ethnic groups exists with a 2 - 3-times higher CVD mortality rate in Pasifika compared to Pākehā. It is unknown whether a difference in cardiac fibrosis might underly this ethnic inequality in CVD mortality. To address this, we determined cardiac fibrosis, myocardial fat infiltration, and the expression of some key miRNAs (miR-15a, miR-15b, miR- 34a and miR-153) in right atrial appendages of Pacific Islanders and New Zealand European patients (n=21) undergoing cardiopulmonary bypass surgery. Cardiac fibrosis was measured by total collagen deposition identified by Picro Sirius Red staining, whereas fat accumulation was determined via Oil-Red-O staining. No differences in cardiac fibrosis were observed between ethnic groups (Collagen: Pasifika 23.4±12.5% vs. New Zealand European 29.4±13.2%, one-way ANOVA, p=0.17). Similarly, no differences were observed in accumulation of lipid nor the expression of the miRNAs examined (-15a, - 15b, -34a and -153) between different groups. In conclusion, the earlier requirements for surgical intervention for CVD of Pasifika in Aotearoa might not be explained by differences in miRNAs associated with cardiomyocyte loss, fibrosis or myocardial lipid infiltration. New and Noteworthy Despite the established significant inequality in the burden of CVD amongst the Pasifika compared to the Pākehā (New Zealand European) populations in Aotearoa, we found no difference inhistopathological (cardiac fibrosis, lipid infiltration, or associated pro- or anti-f

Increased angiogenesis parallels cardiac tissue remodelling in experimental acute Trypanosoma cruzi infection

BACKGROUND Angiogenesis has been implicated in tissue injury in several noninfectious diseases, but its role in Chagas disease (CD) physiopathology is unclear. OBJECTIVES The present study aimed to investigate the effect of Trypanosoma cruzi infection on cardiac angiogenesis during the acute phase of experimental CD. METHODS The signalling pathway involved in blood vessel formation and cardiac remodelling was evaluated in Swiss Webster mice infected with the Y strain of T. cruzi. The levels of molecules involved in the regulation of angiogenesis, such as vascular endothelial growth factor-A (VEGF-A), Flk-1, phosphorylated extracellular-signal-regulated protein kinase (pERK), hypoxia-inducible factor-1α (HIF-1α), CD31, α-smooth muscle actin (α-SMA) and also the blood vessel growth were analysed during T. cruzi infection. Hearts were analysed using conventional histopathology, immunohistochemistry and western blotting. FINDINGS In this study, our data demonstrate that T. cruzi acute infection in mice induces exacerbated angiogenesis in the heart and parallels cardiac remodelling. In comparison with noninfected controls, the cardiac tissue of T. cruzi-infected mice presented higher levels of (i) HIF-1α, VEGF-A, Flk-1 and pERK; (ii) angiogenesis; (iii) α-SMA+ cells in the tissue; and (iv) collagen -1 deposition around blood vessels and infiltrating throughout the myocardium. MAIN CONCLUSIONS We observed cardiac angiogenesis during acute experimental T. cruzi infection parallels cardiac inflammation and remodelling.

The global competitive situation of cardiac tissue engineering based on patent analysis / 中国组织工程研究

BACKGROUND: Tissue engineering is the best way to repair or replace organ failure or tissue defects. From the theoretical point of view to the research in many fields, tissue engineering has developed very rapidly. As cardiovascular disease has become one of the most dangerous factors that endanger human health, research on cardiac tissue engineering has made tremendous progress. OBJECTIVE: To provide advices and references for the development and innovation of cardiac tissue engineering based on patent analysis in the field of cardiac tissue engineering that reveals the global competitive situation of cardiac tissue engineering. METHODS: We qualitatively and quantitatively analyze the number and development tendency, technology birthplaces, target markets, applicants, inventors and technical fields of patents in the field of liver tissue engineering in nearly 20 years. The data visualization method is used to present the current status and tendency of global cardiac tissue engineering technology development and China's development status. RESULTS AND CONCLUSION: The technology for cardiac tissue engineering has been evolved rapidly and highly innovative, with invention patents accounting for 93.91%. The scale of technological development in the field of cardiac tissue engineering in China is not expanded as large as that in the United States, but the growth rate is far faster than that in the United States, and it has accumulated a certain number of high-quality technological achievements, becoming the second largest source of technology in the world. The United States is the most concerned target market in the field of cardiac tissue engineering, and the Chinese market currently ranks fourth. Chinese cardiac tissue engineering has developed rapidly in recent years, growing much faster than that in the United States. There are three institutions in China that has mounted to the front of the world in terms of technology development. Due to a lack of technological achievements with high potential market value, there is still a certain gap between China and the United States. Chinese inventors have achieved certain results in this field, mainly in enterprises. The main fields of technological innovation in this field are heart valve covering materials and cell scaffolds. Through an in-depth and comprehensive analysis of patents in the field of cardiac tissue engineering, it can be found that the global development of cardiac tissue engineering is active and innovative, but generally lacks high-quality results. The United States is the most concerned target market in this field and the most important technology birthplace, whereas China is at a stage of rapid development in this field. In order to improve technological competitiveness, enterprises and universities should strengthen cooperation and focus on research hot spots.

Recent research progress in construction of biomimetic engineered cardiac tissue based on extracellular matrix / 中国组织工程研究

BACKGROUND: Patches, powders and hydrogels fabricated from extracellular matrix and its components can be used as scaffolds, along with a variety of stem cells and their derivatives, to construct biomimetic engineered cardiac tissue. OBJECTIVE: To review research progress in construction of biomimetic engineered cardiac tissue based on extracellular matrix. METHODS: We searched the articles in Web of Science Core Collection and PubMed databases with the key words of “the extracellular matrix; engineered cardiac tissue; cardiomyocyte; biomimetic; stem cell” in English. Eventually 64 articles were included for review. RESULTS AND CONCLUSION: Compared with the traditional synthetic materials, the extracellular matrix has good biocompatibility and cell affinity, which can provide seed cells with the closest living environment, and is conducive to the growth, differentiation and maturation of seed cells. A great number of research evidences suggest that the biomimetic engineered cardiac tissue based on extracellular matrix and stem cells has the characteristics of excitability, contractility and conductivity similar to the natural myocardial tissue. It also can repair the damaged myocardium, reshape the microvascular system and effectively improve cardiac function, showing the potential to treat cardiovascular diseases such as myocardial infarction. However, there are still some problems in the construction of biomimetic engineered cardiac tissue based on extracellular matrix, such as the structural damage during decellularization, the relatively slow development of seed cell morphology and function.

Application of speckle tracing echocardiography in examination of rat models of myocardial infarction and its significance / 吉林大学学报(医学版)

Objective: To investigate the significance of speckle tracing echocardiography in the examination of the rat models of myocardial infarction, and to elucidate the reliability and clinical application of speckle tracing echocardiography in the identification of the myocardial infarction rats. Methods: A total of 50 rats were randonly divided into sham operation group and model group, with 25 rats in each group. Ischemic preconditioning method was used to establish the myocardial infarction models. Speckle tracking echocardiography and cardiac tissue Masson staining were performed to analyze the changes of echocardiography and the morphology of myocardium tissue of the rats. Results: Compared with sham operation group, the each index in echocardiography of the rats in model group before modeling had no significant differences ( Pr>0. 05). Compared with sham operation group∗ the left ventricular ejection fraction (KF), circumferential strain (CS)» the peak values of CS in the anterior septum, anterior wall, anterior lateral wall, systolic period, radial strain ( RS) of the anterior wall of the rats in model group were decreased ( P<0. 05); the standardized time to peak of CS of anterior wall (TTP) was increased ( P<0. 05). The results of Masson staining showed that there was no change in the myocardium tissue and no infarction of the rats in control group; the infarction area of the rats in model group was (4. 52± 1. 41) %•, the infarction located in the anterior wall which was the myocardiocyte lesion in the small area. Conclusion: Speckle tracing echocardiography RS and IIP can reveal the infarction area and its surrounding areas of myocardial infarction, and quantitatively detect the myocardial infarction site in the rats. Speckle tracing echocardiography can be used for the clinical rapid diagnosis of myocardial infarction and confirmation of infarction area.

Role of adenovirus-mediated cardiac-specificRIP140 overexpression in cardiac function and inflammation pathway / 中国药理学通报

Aim To explore the role of cardiac-specific overexpression of RIP140 in cardiac function and inflammation signaling pathway.Methods Direct intra-myocardial injection of adenovirus vector expressing RIP140 drove transgene expression in heart tissue.RIP140 overexpression was confirmed using immunofluorescence technique in heart.Cardiac function was assessed by echocardiographic and hemodynamic assessment.TNF-α,IL-2 and IL-1β inflammatory cytokines were detected by ELISA,and the protein levels of p65 and IκB-α were measured by Western blot.Results Adenovirus-mediated foreign gene of RIP140 was successfully transferred in cardiac tissue.RIP140 overexpression in heart induced ventricular dilation,decreased left ventricular ejection fraction and cardiac malfunction,as well as increased releases of TNF-α,IL-2 and IL-1β inflammatory cytokines,p65 protein translocation into the nucleus and IκB-α protein degradation in cytoplasm.Conclusion Adenovirus-mediated RIP140 overexpression in cardiac tissue impairs cardiac function,activates NF-κB/p65 inflammatory signaling pathway and induces the release of inflammatory cytokines.

A comparative study of biventricular and right ventricular septum pacing in the patients with pacemaker dependant Jianping / 中国综合临床

Objective Respectively applying the treatment of biventricular pacing and right ventricular septal pacing in atrioventricular block,to compare the heart function influence of two kinds of pacing mode on pacemaker dependent patients, to provide evidence for the physiological pacing mode selection?Methods Enrolled 20 patients from January 2012 to March 2013 who should be placed in pacemakers, their primary disease was the second degree,high or third degree atrioventricular block,giving them three chamber pacemaker ( right atrial + biventricular ) each?Randomly divided into right ventricular septum pacing group ( group A, n=10) and biventricular pacing group( group B,n=10)?Twelve months later,each group crossed into the each other group and continued following?up for 12 months?After 24 months to obtain all the data to do the statistical analysis,including patients'6 min walking distance(6MWD),the Minnesota Heart Failure Quality of life score (MLHFQ),plasma N?terminal pro brain natriuretic peptide precursor(NT?proBNP),left ventricular ejection ejection fraction(LVEF),left ventricular diastolic end diastolic diameter(LVEDD),left ventricular contraction end diastolic diameter(LVESD),left ventricular twelve segmental 14W time standard deviation(Ts?12SD),left ventricular twelve segmental 14W time maximum delay(Ts?dif),the paced QRS qrsd?Results Compared with group B,the 6MWD and LVEF of 12,24 months after treatment of group A were significantly increased( ( 242?58 ±37?56) m vs?(347?42±36?59) m vs?(340?67±24?99) m;(39?97±5?84)% vs?(57?92±10?01)% vs?(60?50±10?06)%;P0?05)?Conclusion Compared with the right septal pacing,biventricular pacing is of no significant advantages on the effect of cardiac function for patients with pacemaker dependent.

Respuesta cardiaca al estrés tóxico por exposición pasiva combinada al humo de cigarrillo y al etanol / Cardiac stress toxic response to combined passive smoke cigarette exposition plus ethanol

El estrés oxidativo ha sido considerado por muchos investigadores como la principal causa de daño tisular generado por el consumo de alcohol en combinación con nicotina. Sin embargo, se desconoce si existe una potenciación de la inducción de Hsps como respuesta al daño celular en el caso de fumadores involuntarios que consumen etanol, y si los sistemas de citoprotección endógena, específicamente la proteína anti-estrés Hsp70, tienen alguna participación. En tal sentido, en este trabajo se determinó la presencia de las Hsp70 y su correspondencia con la respuesta subcelular cardiaca en el estrés tóxico individual y combinado de etanol y exposición pasiva al humo del cigarrillo (EPHC) en ratas. Se utilizaron 60 ratas hembras Sprague-Dawley (80- 100gr), divididas aleatoriamente en cuatro grupos: grupo control; grupo etanol (2 g/kg p.c. 50%, vía oral); grupo humo (exposición pasiva al humo de 8 cigarrillos) y grupo combinado (etanol-humo). Los tratamientos se suministraron diariamente en dosis única, durante 15 días continuos. Seguidamente, posterior al sacrificio de los animales se tomaron muestras de la pared ventricular izquierda del corazón para el estudio bioquímico y subcelular. Los resultados mostraron un paralelismo entre la mayor acumulación de Hsp70 y el menor daño subcelular en el tejido cardiaco. El tratamiento combinado de alcohol y EPHC promovió la respuesta al estrés en el corazón, a través de un proceso de coinducción, resultando en mayor acumulación de Hsp70. Se sugiere un papel cardioprotector de las Hsp70.

Many researchers have considered oxidative stress as the main cause of tisular damage induced by alcohol and nicotine together. Oxidative stress is associated to the induction of stress proteins. However, in the case of passive smoke, it is unknown whether the stress proteins are induced and what kind of role they could have. In this regard, this work determined Hsp70 and their relationship to subcellular heart response in individual and combined ethanol and passive smoke cigarette exposition in rats. 60 female Sprague-Dawley (80-100g) rats, were randomized into four group: control; ethanol (2 g/kg c.w. 50%, oral route); passive smoke of 8 cigarettes and ethanol/smoke group. Single dose daily treatment was given during 15 days. Once therats were killed, samples for biochemical and subcellular analysis were made from left ventricular wall. Results showed a strong relationship between bigger accumulation of Hsp70 and smaller cardiac cellular damage. Ethanol plus passive smoke treatment promoted the stress response by co-induction and an increased Hsp70 accumulation was induced. It is suggested a cardiac protective role for Hsp70.

Changes of ANF mRNA expression in the myocardial tissue of rat embryo and suckling induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin / 第三军医大学学报

Objective To investigate the changes of ANF mRNA expression in the myocardial tissues of rat embryo and neonate induced by 2,3,7,8-TCDD so as to determine if TCDD can cause injuries of cardiac functions. Methods SD rat embryos were divided into 4 groups respectively exposed to TCDD at the dose of 0.05,0.5,5,10 ?g/kg. The mRNA expression of ANF/ANP in the myocardial tissues of rat embryos of day 15,19 and suckling rats aged 5 days were detected by semiquantitative RTPCR analysis. Results TCDD could upregulate ANF mRNA expression in the myocardial tissues of rat embryos and suckling rats,as compared with control group. Conclusion TCDD can upregulate ANF mRNA expression in myocardial tissues,suggesting that TCDD may cause injuries of cardiac functions of rat embryos and suckling rats.