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Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.
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Objective To investigate the clinical characteristics of coronary heart disease risk fac tors,and explore the relationship of severity of coronary artery lesions in patients with coronary heart disease and coronary heart disease risk factors.Methods In our hospital for treatment of coronary artery disease patients during April 2013 to August 2014,230 cases of hospitalized patients were divided into two groups after coronary angiography diagnosis,including 170 cases of patients with coronary heart disease as the observation group,and 60 patients with coronary atherosclerosis as the control group with the degree of stenosis less than 50％.The clinical data of two groups were used to study the risk factors for coronary heart disease.The relationship was analyzed between severity of coronary artery pathological changes and coronary heart disease risk factors.Results For the observation group,type 2 diabetes,smoking,and men were associated with coronary heart disease (CHD),with the corresponding OR (95％ CI) of 17.489 (11.013-30.017),48.632 (20.379-117.178),and 18.976 (13.105-28.331),respectively.Smoking and type 2 diabetes were associated with coronary artery stenosis degree (P ＜ 0.05),with OR 95％ (CI) of 10.15 (2.012-2.584),and of 7.23 (1.613-2.176).The results found there was no relationship among hypertension,dyslipidemia,coronary heart disease (CHD),and age.There was a link between the body mass index (BMI) and the severity of the disease.For observation group,left ventricular ejection function,high-sensitivity C-reactive protein (hs-CRP),and Ccr were related to the severity of coronary lesions,and the patients existed lower Ccr,left ventricular ejection function abate,and increased hs-CRP levels increase,P＜0.05,and the OR (95％ CI) were 1.986 (5.204-17.627),1.103 (1.012-1.027),and 2.131 (1.901-2.369).Conclusions Type 2 diabetes,smoking,male patients with coronary heart disease risk factors had a close relationship,and the severity of coronary artery lesions included the reduced re nal function in patients and the increased hs-CRP level.
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Coronary heart disease is the main cause of death,and harmful to the health of the elderly,affecting the quality of life of the elderly.Coronary stent treatment with its safety,minimally invasive,simplistic characteristics in the past 40 years has become the focus of coronary therapy development.At present,the bioresorbable scaffolds made of biodegradable materials have been developed,and magnesium alloy scaffolds have been developed rapidly as one of the representative materials.This article reviewed the progress of clinical research on bioresorbable magnesium alloy coronary stents in recent years,summarized stent development process,and thought about the future development of intervention and treatment of the future.
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Coronary heart disease is the main cause of death,and harmful to the health of the elderly,affecting the quality of life of the elderly.Coronary stent treatment with its safety,minimally invasive,simplistic characteristics in the past 40 years has become the focus of coronary therapy development.At present,the bioresorbable scaffolds made of biodegradable materials have been developed,and magnesium alloy scaffolds have been developed rapidly as one of the representative materials.This article reviewed the progress of clinical research on bioresorbable magnesium alloy coronary stents in recent years,summarized stent development process,and thought about the future development of intervention and treatment of the future.
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BACKGROUND:Novel fuly biodegradable poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) scaffold shows a good prospect of application, but whether the scaffold material has impact on the surrounding tissue calcification is unknown. OBJECTIVE: To observe the influence of PLLA/ACP scaffold material on the calcification of surrounding tissue after implantation of PLLA/ACP scaffold into rats. METHODS:A total of 48 SD rats were divided into experimental group and control group randomly. The experimental group was implanted with PLLA/ACP scaffold material, while the control group was implanted with PLLA scaffold material. At 1, 2, 4, 12 weeks after implantation, the liver function, kidney function and concentrations of calcium, phosphorus, alkaline phosphatase in serum were detected; the muscle tissue around the scaffold was colected for hematoxylin-eosin staining, Von Kossa staining, alkaline phosphatase staining and immunohistochemical staining of nuclear factor-kappa B. Then, western blot assay was used to detect the contents of interleukin-6, bone morphogenetic protein-2, and meanwhile, the contents of calcium and alkaline phosphatase in tissue homogenate were measured. RESULTS AND CONCLUSION:There was no significant difference in either group about the liver and kidney functions at each time. The content of interleukin-6 in the experimental group was less than that in the controlgroup at 2, 4 and 12 weeks after implantation (P 0.05). These findings indicate that the PLLA/ACP scaffold has a good biocompatibility and biological security, which cannot induce peripheral tissue calcification.
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BACKGROUND:In recent years, pathological calcification such as vascular calcification has been an active deposition of the mineralizer in the abnormal parts, can promote the occurrence and development of many diseases. Moreover, extensive studies believe that micro-inflammatory state is strongly associated with pathological calcification. OBJECTIVE:To further summarize the relationship between micro-inflammatory state and calcification based on the relationship between inflammatory factor and calcification-related factors. METHODS: A computer-based search of CNKI, Wanfang database and PubMed database from January 2000 to January 2015 was performed for articles addressing the relationship between micro-inflammatory state and calcification. The key words were “calcification, micro-inflammatory state, inflammatory factor” in Chinese and English. RESULTS AND CONCLUTION:Micro-inflammatory state is a non-dominant inflammatory state, caused by an infection of non-pathogenic microorganisms, mainly for the elevated inflammatory protein, inflammatory cytokines in the systemic circulation. At present, pro-inflammatory cytokines interleukin-1, interleukin-6, interleukin-8, tumor necrosis factor-alpha and acute phase protein C reactive protein were considered as the objective and sensitive detection index of micro-inflammation state. A large number of studies have found that a slight elevation of interleukin-1, interleukin-6, interleukin-8, tumor necrosis factor-alpha and C reactive protein was positively correlated with calcification promoting factors, which ilustrated that the micro-inflammatory state has the role of promoting the calcification.
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BACKGROUND:With good biocompatibility, bioactivity, control able biodegradation rate, amorphous calcium phosphate is considered as a natural reservoir of calcium and phosphorus, which has been widely used in the biomedical field. OBJECTIVE:To review the latest progress of amorphous calcium phosphate in biomedicine based on its clinical application and characteristics. METHODS:A computer-based search of CNKI, Wanfang database and PubMed database from January 1980 to June 2014 was performed for articles relevant to amorphous calcium phosphate materials with the key words of“amorphous calcium phosphate, biomaterials”in Chinese and English. RESULTS AND CONCLUSION:Amorphous calcium phosphate has been widely used in orthodontic care, bone substitutes, drug delivery material and stents, but it is stil in the developmental stage for the special low differentiated cells, cytokines, targeted drug delivery materials and new biodegradable coronary stent. Based on amorphous calcium phosphate, there are various possible treatments for human diseases. But we cannot blindly exaggerate its advantages but outweigh its disadvantages. For example, whether it wil increase the formation of dental calculus during prevention of dental caries? Whether it wil promote its adjacent tissue calcification or hardening? And whether there are risks leading to vascular calcification or hardening? The advantages and disadvantages of amorphous calcium phosphate when used in human are stil needed to carry out a large scale and long-time research.
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BACKGROUND:In order to solve the problems of poly-l-lactic acid (PLLA) stents, such as poor support, acidic metabolites, we researched a novel biogradable stent-PLLA/amorphous calcium plosphate (ACP). OBJECTIVE: To discuss the safety and histocompatibility of the novel biogradable stent-PLLA/ACP stent implanted in the coronary artery in a porcine model. METHODS:Sixteen novel biogradable stents were randomly implanted into the coronary arteries, left anterior descending branch, left circumflex artery or right coronary artery of sixteen healthy Tibet miniature pigs. The blood routine and blood biochemistry were measured pre-operation and at 1 month after operation. The coronary blood vessels where the stent was implanted were examined by hematoxylin-eosin staining at 1 and 6 months after operation. RESULTS AND CONCLUSION: Compared with pre-operation, the post-operation indicators of the blood routine and blood biochemistry were of no significant difference. Coronary angiography revealed coronary artery patency and no thrombosis, the vascular stent segments exhibited clear boundaries with the surrounding tissue, with no tissue adhesion, necrosis, and adherence abnormalities. The results of hematoxylin-eosin staining showed that there was no significant difference in vascular injury integral between 1 month after operation and 6 months after operation. However, 6 months after operation, the scores of the inflammation were lower (P < 0.05), and the scores of the endothelialization were increased (P < 0.05). There was no myocardial infarction and inflammatory cellinfiltration around the stent. These results suggest that the novel biodegradable stent has good safety and histocompatibility.
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BACKGROUND:At present, the main research fields about coronary stents are the whole degradation biological materials with high biocompatibility and drug control ed release systems. OBJECTIVE: To evaluate the safety after the two novel biodegradable stents implanted in coronary arteries in porcine models. METHODS:The normal ful y biodegradable stents were made up of the poly-L-lactide and the antiproliferative drugs paclitaxel, and the novel biodegradable stents were added in amorphic calcium phosphate at the basis of normal biodegradable stents. (1) Five normal ful y biodegradable stents were randomly implanted into the coronary arteries of five porcines, and five novel biodegradable stents were randomly implanted into the coronary arteries of the remaining five porcines by coronary angiography. The blood biochemistry and C-reactive protein levels were measured pre-operation and at 28 days after operation. Coronary angiography was utilized to observe the lumen unobstructed at 28 days after surgery. (2) Under a microscope, seven normal ful y biodegradable stents and seven novel biodegradable stents were implanted into right external iliac arteries of 14 rabbits. Blood urea nitrogen and creatinine levels were measured before surgery and at 28 days after operation. RESULTS AND CONCLUSION:At 28 days after operation, there were no significant changes in porcine glutamic-pyruvic transaminase, aspartate aminotransferase, triacylglycerol, total cholesterol, low density lipoprotein and C-reactive protein levels compared with that before operation, but urea nitrogen and creatinine levels were significantly higher than that before operation (P<0.05). The result of coronary angiography showed that no in-stent thrombosis or stenosis was detected in either group. There was no significant difference in urea nitrogen and creatinine levels in both groups. These results suggested that it is safe and compatible after the two novel biodegradable stents implanted in coronary arteries of porcine models, and the stents had good histocompatibility.
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Objective To evaluate the efficacy of percutaneous transluminal septal myocardial ablation (PTSMA) and septal myectomy (SM) for treatment of hypertrophic obstructive cardiomyopathy.Methods We searched all clinical controlled trials of PTSMA and SM in treatment of hypertrophic obstructive cardiomyopathy in Cochrane Library,PubMed,Web of Science,Wanfang Database and CNKI update to August,2012.The selected studies in Chinese and English were used for Meta-analysis with software RevMan 5.0.Results Five studies including 286 cases (PTSMA:149,SM:137) were included in the study.Left ventricular outflow tract pressure was significantly reduced by SM treatment compared with PTSMA (OR =9.07,95％ CI:0.96-17.18,P =0.030).There were no significant differences in interventricular septum thickness (OR =1.15,95％ CI:-0.79-3.10,P =0.240),left atrial diameter (OR =1.95,95％ CI:-0.16-4.07,P =0.070),left ventricular end-diastolic (OR =0.70,95％ CI:-0.79-2.19,P =0.360),end systolic diameter (OR =1.14,95 ％ CI:-1.65-3.93,P =0.420),degree of symptom improvement (chest pain:OR =1.07,95 ％ CI:0.35-3.23,P =0.910;syncope:OR =0.32,95％ CI:0.08-1.23,P =0.100),and postoperative mortality (OR =1.63,95％CI:0.46-5.76,P =0.450) between PTSMA and SM treatment; but the rates of pacemaker implantation (OR =5.91,95％ CI:2.04-17.11,P =0.001) and reintervention treatment (OR =6.62,95％CI:1.20-36.62,P=0.030) in patients with PTMSA were significantly higher than those with SM.Conclusions There is no evidence to indicate that PTSMA can completely replace SM,as an alternative choice the therapy can be used according to left ventricular out flow tract pressure,symptoms,anatomy of target vessel and other conditions.