There is overwhelming evidence that hypertension is an important risk factor for both macrovascular and microvascular complications in patients with diabetes, but the problem remains to identify appropriate goals for preventive therapies. A number of guidelines (the European Society of Cardiology (ESC)/European Association for the Study of Diabetes (EASD) 2007, the Joint National Committee (JNC)-VII 2003, the American Diabetes Association (ADA) 2011) have for example advocated a blood pressure goal of less than 130/80 mmHg, but this suggestion has been challenged by findings in recent trials and meta-analyses (2011). The European Society of Hypertension (ESH) therefore recommends a systolic blood pressure goal of “well below” 140 mmHg. Based on evidence from both randomized controlled trials (hypertension optimal treatment (HOT), action in diabetes and vascular disease: preterax and diamicron MR controlled evaluation (ADVANCE), action to control cardiovascular risk in diabetes (ACCORD)) and observational studies (ongoing telmisartan alone and in combination with ramipril global endpoint trial (ONTARGET), international verapamil-trandolapril study (INVEST), treat to new targets (TNT), and the National Diabetes Register (NDR)), it has been shown that the benefit for stroke reduction remains even at lower achieved blood pressure levels, but the risk of coronary events may be uninfluenced or even increased at lower systolic blood pressure levels. In a recent meta-analysis, it was therefore concluded that the new recommended goal should be 130–135 mmHg systolic blood pressure for most patients with type 2 diabetes. Other risk factors should also be controlled with a more ambitious strategy applied in the younger patients with shorter diabetes duration, but a more cautious approach in the elderly and frail patients with a number of vascular or non-vascular co-morbidities. In patients from East Asia, such as China, the stroke risk is relatively higher than the risk of coronary events. This must also be taken into consideration for individualized goal setting in relation to total risk, for example in patients from stroke-prone families. In conclusion, the current strategy is to have a more individualized approach to risk factor control in patients with type 2 diabetes, also relevant for blood pressure control.

Angiotensin II (AngII) is the primary bioactive peptide of the renin angiotensin system that plays a critical role in many cardiovascular diseases. Subcutaneous infusion of AngII into mice induces the development of abdominal aortic aneurysms (AAAs). Like human AAAs, AngII-induced AAA tissues exhibit progressive changes and considerable heterogeneity. This complex pathology provides an impediment to the quantification of aneurysmal tissue composition by biochemical and immunostaining techniques. Therefore, while the mouse model of AngII-induced AAAs provides a salutary approach to studying the mechanisms of the evolution of AAAs in humans, meaningful interpretation of mechanisms requires consideration of the heterogeneous nature of the diseased tissue.

Reperfusion is the key strategy in acute ST-segment elevation myocardial infarction (STEMI) care, and it is time-dependent. Shortening the time from symptom to reperfusion and choosing the optimal reperfusion strategy for STEMI patients are great challenges in practice. We need to improve upon the problems of low reperfusion rate, non-standardized treatment, and economic burden in STEMI care. This article briefly reviews the current status of reperfusion strategy in STEMI care, and also introduces what we will do to bridge the gap between the guidelines and implementation in the clinical setting through the upcoming China STEMI early reperfusion program.

As life expectancy increases, valvular heart disease is becoming more common. Management of heart disease and primarily valvular heart disease is expected to represent a significant proportion of healthcare provided to the elderly population. Recent years have brought a progression of surgical treatments toward less invasive strategies. This has given rise to percutaneous approaches for the correction of valvular heart disease. Percutaneous mitral valve repair using the MitraClip system (Abbott Vascular, Santa Clara, CA, USA) creates a double orifice and has been successfully used in selected patients with mitral regurgitation. We review the rationale, procedural aspects, and clinical data thus far available for the MitraClip approach to mitral regurgitation.

Objective: To evaluate whether liposomal prostaglandin E1 (lipo-PGE1) can decrease reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI). Methods: Twenty-two male Chinese mini-swines were randomized into three groups: six in a sham-operation group, and eight each in the control and lipo-PGE1 groups. The distal part of the left anterior descending coronary artery (LAD) in the latter two groups was completely occluded for 2 h, and then reperfused for 3 h. Lipo-PGE1 (1 μg/kg) was injected 10 min before LAD occlusion until reperfusion for 1 h in the lipo-PGE1 group. Hemodynamic data and proinflammatory cytokines were examined before AMI, 2 h after occlusion, and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining were performed to evaluate the myocardial no-reflow area (NRA). Results: Left ventricular systolic pressure and end-diastolic pressure significantly improved in the lipo-PGE1 group after reperfusion compared with the control group and also 2 h after AMI (P<0.05 for both). MCE and double staining both showed that lipo-PGE1 decreased reperfusion NRA after AMI (P<0.05, P<0.01). Lipo-PGE1 decreased serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) after myocardial infarction reperfusion (P<0.05 for both). Conclusions: Lipo-PGE1 is cardioprotective in our porcine model of myocardial infarction reperfusion no-reflow, decreasing NRA and attenuating the inflammatory response.

Objective: To study whether Tongxinluo (TXL) can induce angiogenesis in bone marrow mesenchymal stem cells (MSCs), and to investigate the underlying mechanism. Methods: Bone marrow MSCs were obtained from male Sprague-Dawley rats. We established an angiogenesis model in vitro via matrigel experiment. MSCs were seeded on matrigel coated 24-well plates, and treated by TXL 50 and 100 mg/L. After 24 h, we observed the tube formations of MSCs in the matrigel. Cell migration ability was examined by wound scratch test and transwell assay. Expressions of vascular endothelial growth factor (VEGF), fetal liver kinase-1 (Flk-1), matrix metalloproteinase-2 (MMP-2), MMP-9, and tissue inhibitor of metalloproteinase-2 (TIMP-2) were analyzed at the protein level by Western blot. Gelatin zymography assay was applied to investigating the MSC paracrine abilities of pro-MMP-2 and activated MMP-2. Results: TXL promoted MSC tube formation in matrigel. The ratio of TXL 100 mg/L treated-MSC tubular length was increased 3.04-fold compared to the control group (P<0.05). Scratch test and transwell assay showed that TXL could improve the cell migration ability of MSCs. Western blot experiments showed that TXL promoted MSC synthesis of MMP-2, but it had no influence on the expressions of MMP-9 and TIMP-2. This effect was confirmed by gelatin zymography assay, which showed that TXL increased MSC secretion of pro-MMP-2 and activated MMP-2. VEGF expression of TXL treated-MSCs was increased compared to the control group. The expression of Flk-1 was not different among the groups. Conclusions: This study demonstrates that TXL can promote the tube formation of MSCs, and the underlying mechanisms are associated with increased migration ability of MSCs and the up-regulation of MMP-2 and VEGF expressions.

Objective: Advanced glycation end-products (AGEs) exert inflammatory and oxidative stress insults to produce diabetic nephropathy mainly through the receptor for AGEs (RAGE). This study aimed to assess the effect of atorvastatin on diabetic nephropathy via soluble RAGE (sRAGE) and RAGE expressions in the rat kidney. Methods: Thirty-two male Sprague-Dawley rats were divided into four groups based on the presence or absence of streptozotocin-induced diabetes with or without atorvastatin treatment (10 mg/kg for 24 weeks). Serum sRAGE and glycated albumin (GA) levels were measured with enzyme-linked immunosorbent assay (ELISA) and improved bromocresol purple methods. Renal AGEs, RAGE, endogenous secretory RAGE (esRAGE), and sRAGE were determined with reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Results: Mesangial expansion and microalbuminuria were aggravated in diabetic rats, and improved with atorvastatin treatment. Serum sRAGE levels were lower in diabetic than in normal rats. After atorvastatin treatment, serum and renal sRAGE levels were up-regulated, while renal RAGE expression was decreased in diabetic rats, associated with a reduction in accumulation of AGEs, though renal esRAGE mRNA expression was not significantly increased. Conclusions: Atorvastatin exerted a beneficial effect on diabetic nephropathy with reduced AGE accumulation, down-regulating RAGE expression and up-regulating sRAGE in the kidney.

Objective: The gene for mast cell chymase (CMA1) is an ideal candidate for investigating the genetic predisposition to coronary heart disease (CHD), as activated mast cells have been found to be present in a greater proportion in the shoulder region of atheroma than in normal coronary intimae. Previous studies have indicated that CMA1 promoter polymorphism rs1800875 may be involved in regulating immunoglobulin E (IgE) levels in patients with eczema, and it is associated with the progression of immunoglobulin A nephropathy. Methods: The association between single nucleotide polymorphism (SNP) rs1800875, serum chymase, and serum IgE levels was examined in 175 CHD subjects and 95 non-CHD subjects. Results: Statistical analysis indicated no significant difference in allele frequency between CHD and non-CHD. However, a significant association was found between CMA1 genotypes and total IgE levels in CHD subjects. Meanwhile, crossover analysis revealed that, in GG homozygotes, CHD risk was nearly six times higher in those with IgE (U/ml) level <2.58 (natural logarithm conversion), while no association was found with chymase level. Conclusions: Polymorphism rs1800875 of CMA1 may be associated with serum IgE level in CHD subjects, but not with chymase level in both groups. In GG homozygotes, high IgE level is a protective factor against coronary disease.

The current study was designed to investigate the mechanisms by which ropivacaine may act within the central nervous system (CNS) to produce cardiotoxicity. Eighty New Zealand rabbits were divided into four groups randomly. In Group 1, 20 rabbits received intracerebroventricular (icv) saline, and then received icv ropivacaine 30 min later. In Group 2, 20 rabbits received icv ropivacaine. Whenever dysrhythmias continued for more than 5 min, 0.1 ml saline was administered into the left cerebral ventricle. Ten minutes later, 0.1 ml midazolam was given into the left lateral ventricle. In Group 3, 20 rabbits received icv ropivacaine, and once the dysrhythmias developed, the inspired isoflurane concentration was increased from 0.75% to 1.50%. In Group 4, 20 animals received an intravenous (iv) phenylephrine infusion until dysrhythmias occurred. In Group 1, the rabbits did not develop dysrhythmias in response to icv saline, whereas dysrhythmias did develop in these animals after icv ropivacaine. In Group 2, icv saline had no effect on the dysrhythmias; however, icv midazolam terminated cardiac dysrhythmias. In Group 3, an increase in the concentration of the inspired isoflurane had no effect on dysrhythmias. In Group 4, icv midazolam had no effect on dysrhythmias in response to iv phenylephrine. Ropivacaine administered directly into the CNS is capable of producing cardiac dysrhythmias; midazolam terminated dysrhythmias presumably by potentiation of γ-aminobutyric acid (GABA) receptor activity. Our results suggest that ropivacaine produces some of its cardiotoxicity not only by the direct cardiotoxicity of the drug, but also by the CNS effects of ropivacaine.

Decreased glucose tolerance and diabetes are frequently observed in advanced liver cirrhosis patients and may be related to insulin resistance. Glucose transporter-4 (GLUT4), one of the most important glucose transporters, plays a key role in the development of type 2 diabetes. In order to study the mechanism of insulin resistance in liver cirrhosis patients, we measured the insulin sensitivity index and determined the GLUT4 protein and mRNA contents of skeletal muscle by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR), respectively, in normal people and liver cirrhosis patients. The results showed that the levels of glucose, insulin, and C-peptide in two liver cirrhosis groups were higher and the insulin sensitivity index lower than those of the normal control group. The sensitivity of insulin may decrease with the decline of liver function. However, the contents of GLUT4 protein and mRNA in patients with advanced liver cirrhosis were similar to those of normal controls. In conclusion, insulin resistance is observed in patients with advanced liver cirrhosis but may not be correlated with the skeletal contents of GLUT4 protein and mRNA.

Objective: To assess the correlation between expectations of recovery and whiplash patients’ perceptions of injury severity using a simplified instrument. Expectations of recovery have been shown to predict rate of recovery from whiplash injury in population-based studies. The perception of having more severe pathology or more ominous diagnostic labels has also been associated with a worse prognosis. Methods: Consecutive patients with whiplash-associated disorder grade 1 or 2, presenting in the acute stage to a primary care centre, were asked “do you think that your injury will…” with response options “get better soon; get better slowly; never get better; don’t know.” Injury severity perception (ISP) was measured with a numerical rating scale which ranged from 0–10, on which subjects were asked to rate how severe (in terms of damage) they thought their injury was. The anchors were labeled “no damage” (0) and “severe, and maybe permanent damage” (10). The primary outcome measure was the correlation between the subject’s ISP score and expectation of recovery. Results: A total of 94 subjects (34 males, 60 females, and mean age (40.6±10.0) years, range 19–60 years) were included. The initial responses to expectation of recovery were: get better soon (29/94); get better slowly (22/94); never get better (11/94); don’t know (32/94). The mean ISP score was 4.9±1.7 (range 2–9 out of 10). There was a high correlation between expectations and ISP scores (Spearman’s rank correlation coefficient 0.68). Those who expected to recover soon and those who expected to get better slowly had the lowest ISP scores. Conclusions: The more slowly whiplash patients expect to recover, or the less sure they are of recovery, the more severe their initial perceptions of injury.