Safety and effectiveness of nano composite hydrogel stent implantation in the treatment of coronary cardiovascular disease: A preclinical study.

With the improvement of people's quality of life, various cardiovascular diseases are the most common diseases. Therefore, the main site of disease atherosclerosis is blood vessels, so we can see that its flow rate has obvious changes. Through the analysis of coronary heart disease, this paper studies the relationship between coronary artery disease and cardiovascular disease, which is helpful to evaluate the risk of disease, and also provides the best prevention and treatment plan to overcome cardiovascular disease. As the material of artificial cartilage repair, nanocomposite hydrogel has excellent application value and attraction, because nanocomposite hydrogel has a structure similar to the extracellular matrix of natural chondrocytes. The patients in the experimental group were treated with nano composite hydrogel stent implantation. The other group of patients used the traditional way to carry out the comparative experiment. In the perfusion data of each ventricular wall in the coronary angiography and anterior wall perfusion group, the percentage of lateral wall in the normal proportion was the highest, 69.2%, 59.3% in the anterior wall, 39.5% in the inferior wall, and 19.7% in the apical value and interval. The percentage of LAD stenosis in anterior wall perfusion was O. The highest percentage in the lateral wall was 69.2%, and the lowest in the septum and apex was 19.7%. Nanocomposite hydrogel stent implantation can effectively treat coronary heart disease. The research shows that it is safe and effective in application.

Vaspin Mediates the Intraorgan Crosstalk Between Heart and Adipose Tissue in Lipoatrophic Mice.

Lipoatrophy is characterized as selective loss of adipose tissues, leading to the severity of cardiovascular disorders. Therefore, there was close intraorgan crosstalk between adipose tissue and cardiovascular in lipoatrophy. A-ZIP/F-1 mouse, a well-established lipoatrophic model, and primary cardiomyocytes were used for investigating the pathophysiological changes and molecular mechanisms. A-ZIP/F-1 mice had severe fat loss and impaired ventricular function during growth, but closely associated with the reduction of circulating vaspin levels. Administration of recombinant vaspin protein improved cardiac structural disorders, left ventricular dysfunction, and inflammatory response in lipoatrophic mice. In detail, vaspin decreased cardiac lipid deposits, but enhanced mitochondrial biogenesis and activities. Interestingly, A-ZIP/F-1 mice transplanted with normal visceral adipose tissues exhibited improvement in cardiac structural remodeling and mitochondrial function. Mechanistically, vaspin increased cardiac AKT activity, which guaranteed the mitochondrial benefits of vaspin in lipoatrophic mice and primary mouse cardiomyocytes. The present study suggested that vaspin possessed biological benefits in attenuating lipoatrophy-induced cardiomyopathy onset, and targeting vaspin/AKT signaling was a potential strategy to maintain heart metabolism.

Clinical Influencing Factors of Acute Myocardial Infarction Based on Improved Machine Learning.

At present, there is no method to predict or monitor patients with AMI, and there is no specific treatment method. In order to improve the analysis of clinical influencing factors of acute myocardial infarction, based on the machine learning algorithm, this paper uses the K-means algorithm to carry out multifactor analysis and constructs a hybrid model combined with the ART2 network. Moreover, this paper simulates and analyzes the model training process and builds a system structure model based on the KNN algorithm. After constructing the model system, this paper studies the clinical influencing factors of acute myocardial infarction and combines mathematical statistics and factor analysis to carry out statistical analysis of test results. The research results show that the system model constructed in this paper has a certain effect in the clinical analysis of acute myocardial infarction.

MiR-599 Protects Cardiomyocytes against Oxidative Stress-Induced Pyroptosis.

Oxidative stress is a crucial factor and key promoter of a variety of cardiovascular diseases associated with cardiomyocyte injury. Emerging literatures suggest that pyroptosis plays a key role in cardiac damages. However, whether pyroptosis contributes to cardiomyocyte injury under oxidative stress and the underlying molecular mechanisms are totally unclear. This study was designed to investigate the potential role of pyroptosis in H2O2-induced cardiomyocyte injury and to elucidate the potential mechanisms. Primary cardiomyocytes from neonatal Wistar rats were utilized. These myocytes were treated with different concentrations of H2O2 (25, 50, and 100 µM) for 24 h to induce oxidative injury. Our results indicated that mRNA and protein levels of ASC were remarkably upregulated and caspase-1 was activated. Moreover, the expressions of inflammatory factors IL-1ß and IL-18 were also increased. Luciferase assay showed that miR-599 inhibited ASC expression through complementary binding with its 3'UTR. MiR-599 expression was substantially reduced in H2O2-treated cardiomyocytes. Upregulation of miR-599 inhibited cardiomyocyte pyroptosis under oxidative stress, and opposite results were found by decreasing the expression of miR-599. Consistently, miR-599 overexpression ameliorated cardiomyocyte injury caused by H2O2. Therefore, miR-599 could be a promising therapeutic approach for the management of cardiac injury under oxidative condition.

TRIF/miR-34a mediates aldosterone-induced cardiac inflammation and remodeling.

Aldosterone, as a major product of renin-angiotensin-aldosterone system (RAAS), determines multiple pathophysiological processes in cardiovascular diseases. The excess inflammatory response is one of the key profiles in aldosterone-mediated cardiac remodeling. However, the potential mechanisms of aldosterone/inflammatory signaling were still not fully disclosed. The present study aimed to investigate whether TIR-domain-containing adapter-inducing interferon-ß (Trif) participated in the aldosterone-induced cardiac remodeling, and to explore potential molecular mechanisms. Trif knockout mice and their littermates were osmotically administrated with aldosterone (50 µg/kg per day) for 21 and 42 days. The cardiac structural analysis, functional parameters, and mitochondrial function were measured. Aldosterone dose- or time-dependently increased the levels of TRIF in primary mouse cardiomyocytes or mouse heart tissues. Trif deficiency protected against aldosterone-induced cardiac hypertrophy, fibrosis and dysfunction. Moreover, Trif deficiency also suppressed aldosterone-induced cardiac inflammatory response and mitochondrial injuries. Mechanistically, overexpression of cardiac microRNAs (miR)-34a reversed the cardiac benefits of Trif deficiency in aldosterone-treated mice. Taken together, Trif/miR-34a axis could provide a novel molecular mechanism for explaining aldosterone-induced cardiac hypertrophy, fibrosis and functional disorders.

Decreased expression of adenosine receptor 2B confers cardiac protection against ischemia via restoring autophagic flux.

Adora2B (adenosine receptor 2B) has been reported as one of the key modulators during cardiac remodeling after acute myocardial infarction (AMI). However, the molecular mechanism involved has not been well investigated. Thus, our study aims to investigate whether Adora2B contributes to cardiac remodeling after AMI and its underlying mechanisms. Adenovirus harboring Adora2B or shAdora2B was injected in the border zone in a mouse model of AMI experimentally produced by permanent ligation of left anterior descending (LAD) coronary artery. Decreased Adora2B expression protected the cardiomyocytes from MI-induced autophagic flux obstacle, improved cardiac function, and reduced fibrosis after MI. Adora2B downregulation attenuated the accumulation of LC3-II and p62, which are autophagy substrate proteins. An adenovirus containing mRFP-GFP-LC3 showed that decreased expression of Adora2B restored the autophagic flux by enhancing autophagosome conversion to autophagolysosome. Also, Adora2B knockdown improved cardiomyocytes' survival and protected mitochondrial function of cardiomyocytes insulted with hypoxia. Notably, the effect of Adora2B on autophagy flux and cardiomyocyte protection could be mitigated by autophagy inhibitor chloroquine. Our results demonstrate that decreased expression of Adora2B protected cardiomyocytes from impaired autophagy flux induced by MI. Modulation Adora2B expression plays a significant role in blunting the worsening of heart function and reducing scar formation, suggesting therapeutic potential by targeting Adora2B in AMI for the infarct healing.

Adipose tissue-derived autotaxin causes cardiomyopathy in obese mice.

The prevalence of obesity is dramatic increased and strongly associated with cardiovascular disease. Adipokines, secreted from adipose tissues, are critical risk factors for the development of cardiomyopathy. Present study aimed to investigate the pathophysiological role of autotaxin in obesity-related cardiomyopathy. In high-fat diet-fed mice, autotaxin was mainly synthesized and secreted from adipocytes. The increased accumulation of cardiac autotaxin was positively associated with cardiac dysfunction in obese mice. Interestingly, specific blockage of adipose tissue autotaxin effectively protected against high-fat diet-induced cardiac structural disorders, left ventricular hypertrophy and dysfunction. Inhibition of autotaxin further improved high-fat diet-induced cardiac fibrosis and mitochondrial dysfunction, including improvement of mitochondrial structure, mass and activities. Our findings demonstrated intervention of adipose tissue biology could influence cardiac modification in obese mice, and adipocyte-derived autotaxin was a potential diagnostic marker and therapeutic target for obesity-related cardiomyopathy.

Parathyroid hormone-related peptide protects cardiomyocytes from oxidative stress-induced cell death: First evidence of a novel endocrine-cardiovascular interaction.

Although there is a growing interest in the molecular cross-talk between the endocrine and cardiovascular systems, the cardiac effects of calcium-regulating hormones (i.e., parathyroid hormone-related peptide (PTHrP)) have not been explored. In this study, we examined the effect of PTHrP on the viability of isolated adult mouse cardiomyocytes subjected to oxidative stress. Myocytes from 19 to 22 week old male 129J/C57BL6 mice were exposed to oxidative insult in the form of H2O2 which led to more than 70% loss of cell viability. Herein we demonstrate, for the first time, that pretreatment with 100 nM PTHrP prior to 100 µM H2O2 incubation prevents H2O2 -induced cell death by more than 50%. Immunoblot analysis revealed H2O2 induction of MKP-1 protein expression while PTHrP decreased MKP-1 expression. Moreover, myocytes derived from MKP1 KO mice were resistant to oxidative injury. No added benefit of PTHrP treatment was noted in MKP-1 null cardiomyocytes. Using specific pharmacological inhibitors we demonstrated that P-p38, P-ERK and P-AKT mediated PTHrP's cardioprotective action. These data provide novel evidence that: i) down-regulation of MKP1 affords profound protection against oxidative stress; and ii) PTHrP is cardioprotective, possibly via down-regulation of MKP-1 and activation of MAPK and PI3K/AKT signaling.

Adenosine A2A and A2B receptors are both required for adenosine A1 receptor-mediated cardioprotection.

All four adenosine receptor subtypes have been shown to play a role in cardioprotection, and there is evidence that all four subtypes may be expressed in cardiomyocytes. There is also increasing evidence that optimal adenosine cardioprotection requires the activation of more than one receptor subtype. The purpose of this study was to determine whether adenosine A(2A) and/or A(2B) receptors modulate adenosine A(1) receptor-mediated cardioprotection. Isolated perfused hearts of wild-type (WT), A(2A) knockout (KO), and A(2B)KO mice, perfused at constant pressure and constant heart rate, underwent 30 min of global ischemia and 60 min of reperfusion. The adenosine A(1) receptor agonist N(6)-cyclohexyladenosine (CHA; 200 nM) was administrated 10 min before ischemia and for the first 10 min of reperfusion. Treatment with CHA significantly improved postischemic left ventricular developed pressure (74 ± 4% vs. 44 ± 4% of preischemic left ventricular developed pressure at 60 min of reperfusion) and reduced infarct size (30 ± 2% with CHA vs. 52 ± 5% in control) in WT hearts, effects that were blocked by the A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (100 nM). Treatments with the A(2A) receptor agonist CGS-21680 (200 nM) and the A(2B) agonist BAY 60-6583 (200 nM) did not exert any beneficial effects. Deletion of adenosine A(2A) or A(2B) receptor subtypes did not alter ischemia-reperfusion injury, but CHA failed to exert a cardioprotective effect in hearts of mice from either KO group. These findings indicate that both adenosine A(2A) and A(2B) receptors are required for adenosine A(1) receptor-mediated cardioprotection, implicating a role for interactions among receptor subtypes.

Dose-dependent cardiac effect of oestrogen replacement in mice post-myocardial infarction.

Hormonal replacement therapy (HRT) has recently been shown to increase the risk of cardiovascular events in women. However, it is not clear whether the adverse effect of HRT is related to dosage and/or the presence of progestin. Using a mouse model of myocardial infarction (MI), we studied the dose-effect of oestrogen replacement on mortality and cardiac remodelling and dysfunction post-MI in the absence of progestin. Six-week-old females were subjected to ovariectomy (OVX). A pellet containing a low, moderate or high dose of 17beta-oestradiol (E(2); 0.42, 4.2 or 18.8 microg day(-1)) or placebo was implanted subcutaneously on the day of OVX. Myocardial infarction was induced 8 weeks later, and cardiac morphology and function were evaluated 8 weeks after MI. We found that E(2) at moderate and high doses adversely affected mortality. A low dose of E(2) that restored plasma oestrogen close to physiological levels had no significant effect on mortality but tended to improve cardiac function and remodelling, associated with reduced fibrosis and increased capillary density. At the moderate dose, E(2) exacerbated cardiac fibrosis, hypertrophy, dysfunction and dilatation, associated with liver and kidney enlargement and ascites. Protein kinase C and extracellular signal-regulated kinase were increased by MI but were not affected by E(2). In summary, E(2) at a low dose tended to be cardioprotective. At increased doses that raised plasma oestrogen far beyond the physiological level, E(2) was detrimental to the heart. Our data suggest that dosage should be an important consideration when studying the effect of oestrogen replacement on the heart.