The Role of Oncostatin M and Its Receptor Complexes in Cardiomyocyte Protection,Regeneration, and Failure

Oncostatin M (OSM), a member of the interleukin-6 family, functions as a major mediator of cardiomyocyte remodeling under pathological conditions. Its involvement in a variety of human cardiac diseases such as aortic stenosis, myocardial infarction, myocarditis, cardiac sarcoidosis, and various cardiomyopathies make the OSM receptor (OSMR) signaling cascades a promising therapeutic target. However, the development of pharmacological treatment strategies is highly challenging for many reasons. In mouse models of heart disease, OSM elicits opposing effects via activation of the type II receptor complex (OSMR/gp130). Short-term activation of OSMR/gp130 protects the heart after acute injury, whereas chronic activation promotes the development of heart failure. Furthermore, OSM has the ability to integrate signals from unrelated receptors that enhance fetal remodeling (dedifferentiation) of adult cardiomyocytes. Because OSM strongly stimulates the production and secretion of extracellular proteins, it is likely to exert systemic effects, which in turn, could influence cardiac remodeling. Compared with the mouse, the complexity of OSM signaling is even greater in humans because this cytokine also activates the type I leukemia inhibitory factor receptor complex (LIFR/gp130). In this article, we provide an overview of OSM-induced cardiomyocyte remodeling and discuss the consequences of OSMR/gp130 and LIFR/gp130 activation under acute and chronic conditions.     

Cannabidiol Downregulates Myocardial de Novo Ceramide Synthesis Pathway in a Rat Model of High-Fat Diet-Induced Obesity

It is known that metabolic disturbances, including obesity, predispose to an increased incidence of cardiovascular diseases. Elevated consumption of dietary fat results in intramyocardial accumulation of lipids and their biologically active derivatives, which can disrupt the contractile function of the heart, its metabolism, and intracellular signaling pathways. Therefore, alternative methods, such as phytocannabinoids, are being sought for the treatment of obesity-related effects. In a model of rodent obesity (seven weeks of high-fat-diet (HFD) regime), we used cannabidiol—CBD therapy (intraperitoneal injections for 14 days; 10 mg/kg). High-performance and gas-liquid chromatographies were applied in order to determine sphingolipids in the heart and plasma as well as Western blotting for protein expression. Two-week CBD administration significantly inhibited the de novo ceramide synthesis pathway in the heart of HFD fed rats by lowering sphinganine and sphinganine-1-phosphate contents. The above reductions were accompanied by markedly diminished expressions of myocardial serine palmitoyltransferase 1 and 2 as well as ceramide synthase 5 and 6 in the HFD group with 2-week CBD treatment. To our knowledge, this research is the first that reveals unknown effects of CBD treatment on the heart, i.e., amelioration of de novo ceramide synthesis pathway in obese rats.     

新产品研发是建陶企业可持续发展的核心

新世纪我国建陶企业在整个国民经济的带动下将进一步发展，入世后经济全球化的市场竞争格局，建陶企业只有走新产口研发之路，严格企业管理，才会在日趋激烈的市场竞争中得以生存和可持续发展。     

Increased HDL Size and Enhanced Apo A-I Catabolic Rates Are Associated With Doxorubicin-Induced Proteinuria in New Zealand White Rabbits

The catabolism and structure of high‐density lipoproteins (HDL) may be the determining factor of their atheroprotective properties. To better understand the role of the kidney in HDL catabolism, here we characterized HDL subclasses and the catabolic rates of apo A‐I in a rabbit model of proteinuria. Proteinuria was induced by intravenous administration of doxorubicin in New Zealand white rabbits (n = 10). HDL size and HDL subclass lipids were assessed by electrophoresis of the isolated lipoproteins. The catabolic rate of HDL‐apo A‐I was evaluated by exogenous radiolabelling with iodine‐131. Doxorubicin induced significant proteinuria after 4 weeks (4.47 ± 0.55 vs. 0.30 ± 0.02 g/L of protein in urine, P < 0.001) associated with increased uremia, creatininemia, and cardiotoxicity. Large HDL2b augmented significantly during proteinuria, whereas small HDL3b and HDL3c decreased compared to basal conditions. HDL2b, HDL2a, and HDL3a subclasses were enriched with triacylglycerols in proteinuric animals as determined by the triacylglycerol‐to‐phospholipid ratio; the cholesterol content in HDL subclasses remained unchanged. The fractional catabolic rate (FCR) of [¹³¹I]‐apo A‐I in the proteinuric rabbits was faster (FCR = 0.036 h^?1) compared to control rabbits group (FCR = 0.026 h^?1, P < 0.05). Apo E increased and apo A‐I decreased in HDL, whereas PON‐1 activity increased in proteinuric rabbits. Proteinuria was associated with an increased number of large HDL2b particles and a decreased number of small HDL3b and 3c. Proteinuria was also connected to an alteration in HDL subclass lipids, apolipoprotein content of HDL, high paraoxonase‐1 activity, and a rise in the fractional catabolic rate of the [¹³¹I]‐apo A‐I.     

心力衰竭治疗药物的表观遗传药理学进展

心力衰竭（heart failure,HF）是心室收缩和（或）舒张功能发生障碍的一种疾病,又称心功能不全,可由多种因素引起,主要表现为心脏结构和功能的异常改变,并以交感神经、肾素-血管紧张素-醛固酮等系统激活为特征。通过临床观察,心衰患者在药物治疗期间存在极大异质性,因此在实际用药时,除了要考虑一般的环境因素,还要顾及遗传背景,尤其是序列不改变的表观遗传学。目前,有报道认为心衰患者的用药反应和DNA甲基化、组蛋白修饰、microRNA等修饰相关,但涉及该领域的研究还不多见,因此本文就近几年心衰治疗药物的表观遗传药理学进展进行一个较为全面的综述。     

Analysis of MTHFR and MTRR Gene Polymorphisms in Iranian Ventricular Septal Defect Subjects

Ventricular septal defect (VSD) is one of the most common types of congenital heart defects (CHD). There are vivid multifactorial causes for VSD in which both genetic and environmental risk factors are consequential in the development of CHD. Methionine synthase reductase (MTRR) and methylenetetrahydrofolate reductase (MTHFR) are two of the key regulatory enzymes involved in the metabolic pathway of homocysteine. Genes involved in homocysteine/folate metabolism may play an important role in CHDs. In this study; we determined the association of A66G and C524T polymorphisms of the MTRR gene and C677T polymorphism of the MTHFR gene in Iranian VSD subjects. A total of 123 children with VSDs and 125 healthy children were included in this study. Genomic DNA was extracted from the buccal cells of all the subjects. The restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) method was carried out to amplify the A66G and C524T polymorphism of MTRR and C677T polymorphism of MTHFR genes digested with Hinf1, Xho1 and Nde1 enzymes, respectively. The genotype frequencies of CC, CT and TT of MTRR gene among the studied cases were 43.1%, 40.7% and 16.3%, respectively, compared to 52.8%, 43.2% and 4.0%, respectively among the controls. For the MTRR A66G gene polymorphism, the genotypes frequencies of AA, AG and GG among the cases were 33.3%, 43.9% and 22.8%, respectively, while the frequencies were 49.6%, 42.4% and 8.0%, respectively, among control subjects. The frequencies for CC and CT genotypes of the MTHFR gene were 51.2% and 48.8%, respectively, in VSD patients compared to 56.8% and 43.2% respectively, in control subjects. Apart from MTHFR C677T polymorphism, significant differences were noticed (p < 0.05) in C524T and A66G polymorphisms of the MTRR gene between cases and control subjects.     

强化降脂与介入治疗在冠心病二级预防中的效果比较

目的 探讨比较强化降脂与介入治疗治疗在冠心病二级预防中的效果。方法 选取2009年1月至2010年1月于我院进行治疗的120例冠心病患者为研究对象,将其随机分为A组(强化降脂组)60例和B组(介入治疗组)60例,后将2组患者的心肌梗死发生率、心绞痛发生率、再次住院率及治疗前及治疗后1个月及3个月的血脂、血清hs-CRP、UA水平进行检测及比较。结果 经研究比较发现,A组的心肌梗死发生率、心绞痛发生率、再次住院率均低于B组,A组治疗后1个月及3个月的血清TG、TC及LDL-C、hs-CRP、UA水平均明显低于B组,而血清HDL-C的水平则高于B组,P均<0.05,均有显著性差异。结论 强化降脂治疗在冠心病二级预防中的效果较好,值得临床推广及应用。     

Intake of ruminant versus industrial trans fatty acids and risk of coronary heart disease – what is the evidence?

Several studies have reported a positive association between intake of trans fatty acids and risk of heart disease. It has been suggested that trans fatty acids from ruminant sources are less detrimental than trans fatty acids from industrial sources. Legislation or advice on limiting trans fatty acids has, in some instances, been restricted to trans fatty acids from industrial sources. However, comparisons of ruminant and industrial trans fatty acids have been based on few studies using relative intake data (e.g. quintiles of intakes). Therefore, we have reviewed data describing the associations between absolute intake (g eaten per day) of ruminant and industrial trans fatty acids and risk of coronary heart disease, and examined the associations graphically. Where direct comparison is possible, there are no differences in risk of coronary heart disease between total, ruminant and industrial trans fatty acids for intakes up to 2.5 g/d. At higher intakes (more than 3 g/d) total and industrial trans fatty acids are associated with an increased risk of coronary heart disease but there is insufficient data available on ruminant trans fatty acids at this level of intake. The scarce data do not support discrimination between ruminant and industrial trans fatty acids in dietary recommendations or legislation.