Assessment of the causal relationship between gut microbiota and cardiovascular diseases: a bidirectional Mendelian randomization analysis.

BACKGROUND: Previous studies have shown an association between gut microbiota and cardiovascular diseases (CVDs). However, the underlying causal relationship remains unclear. This study aims to elucidate the causal relationship between gut microbiota and CVDs and to explore the pathogenic role of gut microbiota in CVDs. METHODS: In this two-sample Mendelian randomization study, we used genetic instruments from publicly available genome-wide association studies, including single-nucleotide polymorphisms (SNPs) associated with gut microbiota (n = 14,306) and CVDs (n = 2,207,591). We employed multiple statistical analysis methods, including inverse variance weighting, MR Egger, weighted median, MR pleiotropic residuals and outliers, and the leave-one-out method, to estimate the causal relationship between gut microbiota and CVDs. Additionally, we conducted multiple analyses to assess horizontal pleiotropy and heterogeneity. RESULTS: GWAS summary data were available from a pooled sample of 2,221,897 adult and adolescent participants. Our findings indicated that specific gut microbiota had either protective or detrimental effects on CVDs. Notably, Howardella (OR = 0.955, 95% CI: 0.913-0.999, P = .05), Intestinibacter (OR = 0.908, 95% CI:0.831-0.993, P = .03), Lachnospiraceae (NK4A136 group) (OR = 0.904, 95% CI:0.841-0.973, P = .007), Turicibacter (OR = 0.904, 95% CI: 0.838-0.976, P = .01), Holdemania (OR, 0.898; 95% CI: 0.810-0.995, P = .04) and Odoribacter (OR, 0.835; 95% CI: 0.710-0.993, P = .04) exhibited a protective causal effect on atrial fibrillation, while other microbiota had adverse causal effects. Similar effects were observed with respect to coronary artery disease, myocardial infarction, ischemic stroke, and hypertension. Furthermore, reversed Mendelian randomization analyses revealed that atrial fibrillation and ischemic stroke had causal effects on certain gut microbiotas. CONCLUSION: Our study underscored the importance of gut microbiota in the context of CVDs and lent support to the hypothesis that increasing the abundance of probiotics or decreasing the abundance of harmful bacterial populations may offer protection against specific CVDs. Nevertheless, further research is essential to translate these findings into clinical practice.

Poor cardiovascular health status among Chinese women.

BACKGROUND: Systematic investigation and analysis of cardiovascular health status (CVHS) of Chinese women is rare. This study aimed to assess CVHS and atherosclerotic cardiovascular disease (ASCVD) burden in the Chinese women physicians (CWP) and community-based non-physician cohort (NPC). METHODS: In this prospective, multicenter, observational study, CVHS using the American Heart Association (AHA) defined 7 metrics (such as smoking and fasting glucose) and ASCVD risk factors including hypertension, hyperlipidemia and type-2 diabetes were evaluated in CWP compared with NPC. RESULTS: Of 5832 CWP with a mean age of 44 ± 7 years, only 1.2% achieved the ideal CVHS and 90.1% showed at least 1 of the 7 AHA CVHS metrics at a poor level. Total CVHS score was significantly decreased and ASCVD risk burden was increased in postmenopausal subjects in CWP although ideal CVHS was not significantly influenced by menopause. Compared to 2596 NPC, fewer CWP had ≥ 2 risk factors (8% vs. 27%, P < 0.001); CWP scored significantly higher on healthy factors, a composite of total cholesterol, blood pressure, fasting glucose (P < 0.001), but, poorly on healthy behaviors (P < 0.001), specifically in the physical activity component; CWP also showed significantly higher levels of awareness and rates of treatment for hypertension and hyperlipidemia, but, not for type-2 diabetes. CONCLUSION: Chinese women's cardiovascular health is far from ideal and risk intervention is sub-optimal. Women physicians had lower ASCVD burden, scored higher in healthy factors, but, took part in less physical activity than the non-physician cohort. These results call for population-specific early and improved risk intervention.

Cathepsin K-deficiency impairs mouse cardiac function after myocardial infarction.

BACKGROUND: Extracellular matrix metabolism and cardiac cell death participate centrally in myocardial infarction (MI). This study tested the roles of collagenolytic cathepsin K (CatK) in post-MI left ventricular remodeling. METHODS AND RESULTS: Patients with acute MI had higher plasma CatK levels (20.49 ±â€¯7.07 pmol/L, n = 26) than those in subjects with stable angina pectoris (8.34 ±â€¯1.66 pmol/L, n = 28, P = .01) or those without coronary heart disease (6.63 ±â€¯0.84 pmol/L, n = 93, P = .01). CatK protein expression increases in mouse hearts at 7 and 28 days post-MI. Immunofluorescent staining localized CatK expression in cardiomyocytes, endothelial cells, fibroblasts, macrophages, and CD4+ T cells in infarcted mouse hearts at 7 days post-MI. To probe the direct participation of CatK in MI, we produced experimental MI in CatK-deficient mice (Ctsk-/-) and their wild-type (Ctsk+/+) littermates. CatK-deficiency yielded worsened cardiac function at 7 and 28 days post-MI, compared to Ctsk+/+ littermates (fractional shortening percentage: 5.01 ±â€¯0.68 vs. 8.62 ±â€¯1.04, P < .01, 7 days post-MI; 4.32 ±â€¯0.52 vs. 7.60 ±â€¯0.82, P < .01, 28 days post-MI). At 7 days post-MI, hearts from Ctsk-/- mice contained less CatK-specific type-I collagen fragments (10.37 ±â€¯1.91 vs. 4.60 ±â€¯0.49 ng/mg tissue extract, P = .003) and more fibrosis (1.67 ±â€¯0.93 vs. 0.69 ±â€¯0.20 type-III collagen positive area percentage, P = .01; 14.25 ±â€¯4.12 vs. 6.59 ±â€¯0.79 α-smooth muscle actin-positive area percentage, P = .016; and 0.82 ±â€¯0.06 vs. 0.31 ±â€¯0.08 CD90-positive area percentage, P = .008) than those of Ctsk+/+ mice. Immunostaining demonstrated that CatK-deficiency yielded elevated cardiac cell death but reduced cardiac cell proliferation. In vitro studies supported a role of CatK in cardiomyocyte survival. CONCLUSION: Plasma CatK levels are increased in MI patients. Heart CatK expression is also elevated post-MI, but CatK-deficiency impairs post-MI cardiac function in mice by increasing myocardial fibrosis and cardiomyocyte death.

The gender difference of utilization of cardiac implantable electronic device in China: data from Arrhythmia Interventional Therapy Data Registry.

BACKGROUND: Cardiac implantable electronic devices (CIEDs) greatly improve survival and life quality of patients. However, there are gender differences regarding both the utilization and benefit of these devices. In this prospective CIED registry, we aim to appraise the gender differences in CIED utilization in China. METHODS: Twenty centers from 14 provinces in China were included in our registry study. All patients who underwent a CIED implantation in these twenty centers between Jan 2015 and Dec 2016 were included. RESULTS: A total of 8570 patients were enrolled in the baseline cohort, including 7203 pacemaker, 664 implantable cardiac defibrillators (ICD) implants and 703 cardiac resynchronization therapy device (CRT/D). Totally, 4117 (48.0%) CIED patients were female, and more than 59% pacemaker patients were female, but women account only one third of ICD or CRT/D implantation in this registry. There were significant differences between genders at pacemaker and ICD indications. Female was more likely received a pacemaker due to sick sinus syndrome (SSS) (63.9% vs. 51.0%, P < 0.001). Female patients receiving an ICD were more likely due to cardiac ion channel disease (29.2% vs. 4.2%, P < 0.001). The percentage of utilization of dual-chamber pacemaker in female patients was significantly higher than male (85.3% vs. 81.1%, P < 0.001). But male patients were more likely received a cardiac resynchronization therapy devices with defibrillator than female (56.5% vs. 41.9%, P = 0.001). In pacemaker patient, male was more likely to have structure heart disease (31.3% vs. 28.0%, P = 0.002). In ICD patient, male patients were more likely to have ischemic heart disease (48.2% vs. 29.2%, P < 0.001). The mean age of women at the time of CRT/D implantation was older than men (P = 0.014). Nonischemic cardiomyopathy (70.9%) was the most common etiology in the patients who underwent the treatment of CRT/D, no matter male or female. CONCLUSIONS: In real-world setting, female do have different epidemiology, pathophysiology and clinical presentation of many cardiac rhythm disorders when compared with male, and all these factors may affect the utilization of CIED implantation. But it also possibility that cultural and socioeconomic features may play a role in this apparent discrimination.

Pharmacological Therapy of Abdominal Aortic Aneurysm: An Update.

BACKGROUND: Abdominal aortic aneurysm (AAA), a progressive segmental abdominal aortic dilation, is associated with high mortality. AAA is characterized by inflammation, smooth muscle cell (SMC) depletion and extracellular matrix (ECM) degradation. Surgical intervention and endovascular therapy are recommended to prevent rupture of large AAAs. Unfortunately, there is no reliable pharmacological agent available to limit AAA expansion. In the past decades, extensive investigations and a body of ongoing clinical trials aimed at defining potent treatments to inhibit and even regress AAA growth. CONCLUSION: In this review, we summarized recent progress of potential strategies, particularly macrolides, tetracyclines, statins, angiotensin converting enzyme inhibitors, angiotensin receptor blocker, corticosteroid, anti-platelet drugs and mast cell stabilizers. We also consider recently identified novel molecular targets, which have potential to be translated into clinical practice in the future.

Efficacy of amiodarone and lidocaine for preventing ventricular fibrillation after aortic cross-clamp release in open heart surgery: a meta-analysis of randomized controlled trials.

OBJECTIVE: The relative preventative efficacy of amiodarone and lidocaine for ventricular fibrillation (VF) after release of an aortic cross-clamp (ACC) during open heart surgery has not been determined. This meta-analysis was designed to systematically evaluate the influence of amiodarone, lidocaine, or placebo on the incidence of VF after ACC. METHODS: Prospective randomized controlled trials (RCTs) that compared the VF-preventative effects of amiodarone with lidocaine, or amiodarone or lidocaine with placebo were included. PubMed, EMBASE, and the Cochrane Library were searched for relevant RCTs. Fixed or randomized effect models were applied according to the heterogeneity of the data from the selected studies. RESULTS: We included eight RCTs in the analysis. Pooled results suggested that the preventative effects of amiodarone and lidocaine were comparable (relative risk (RR)=1.12, 95% confidence interval (CI): 0.70 to 1.80, P=0.63), but both were superior to the placebo (amiodarone, RR=0.71, 95% CI: 0.51 to 1.00, P=0.05; lidocaine, RR=0.63, 95% CI: 0.46 to 0.88, P=0.006). The percentage of patients requiring electric defibrillation counter shocks (DCSs) did not differ significantly among patients administered amiodarone (RR=0.21, 95% CI: 0.04 to 1.19, P=0.08), lidocaine (RR=2.44, 95% CI: 0.13 to 44.02, P=0.55), or the placebo (RR=0.56, 95% CI: 0.25 to 1.25, P=0.16). CONCLUSIONS: Amiodarone and lidocaine are comparably effective in preventing VF after ACC, but the percentage of patients who subsequently require DCSs does not differ among those administered amiodarone, lidocaine, or placebo.

Evaluation of Safety and Efficacy of Qinming8631 DR Implantable Cardiac Pacemaker in Chinese Patients: A Prospective, Multicenter, Randomized Controlled Trial of the First Domestically Developed Pacemaker of China.

BACKGROUND: High cost of imported pacemakers is a main obstacle for Chinese patients suffering from bradyarrhythmia, and a domestically developed pacemaker will help lower the burden. This study aimed to evaluate the safety and efficacy of Qinming8631 DR (Qinming Medical, Baoji, China), the first domestically developed dual-chamber pacemaker of China, compared with a commercially available pacemaker Talos DR (Biotronik, Berlin, Germany) in Chinese patients. METHODS: A prospective randomized trial was conducted at 14 centers in China. Participants were randomized into trial (Qinming8631 DR) and control (Talos DR) groups. Parameters of the pacing systems were collected immediately after device implantation and during follow-ups. The effective pacing rate at 6-month follow-up was recorded as the primary end point. Electrical properties, magnet response, single- and double-pole polarity conversion, rate response function, and adverse events of the pacing system were analyzed. The Cochran-Mantel-Haenszel Chi-square test, paired t-test, and Wilcoxon signed-rank test were used for measuring primary qualitative outcomes and comparing normally and abnormally distributed measurement data. RESULTS: A total of 225 patients with a diagnosis of bradyarrhythmia and eligible for this study were randomly enrolled into the trial (n = 113) and control (n = 112) groups. They underwent successful pacemaker implantation with acceptable postoperative pacing threshold and sensitivity. Effective pacing rates of trial and control groups were comparable both in the full analysis set and the per protocol set (81.4% vs. 79.5%, P = 0.712 and 95.4% vs. 89.5%, P = 0.143, respectively). In both data sets, noninferiority of the trial group was above the predefined noninferiority limit(-9.5%). CONCLUSIONS: This study established the noninferiority of Qinming8631 DR to Talos DR. The safety and efficacy of Qinming8631 DR pacemaker were comparable to those of Talos DR in treating patients with cardiac bradyarrhythmia.

Effect of Tai Chi exercise on blood lipid profiles: a meta-analysis of randomized controlled trials.

OBJECTIVE: Studies have demonstrated that Tai Chi exercise improves blood lipid level with inconsistent results. A meta-analysis was conducted to quantify the effects of Tai Chi on blood lipid profiles in humans. METHODS: We screened the databases of PubMed, EMBASE, Cochrane Library (Central), Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang data, and Clinicaltrials.gov for randomized controlled trials with Physiotherapy Evidence Database (PEDro) score more than 3 points up to June 2015. Six studies involving 445 subjects were included. Most trials applied 12-week Tai Chi intervention courses. RESULTS: In comparison with the control group, blood triglyceride (TG) level difference between follow-up and baseline was statistically significantly lower in the Tai Chi practicing group (weighted mean difference (WMD) -16.81 mg/dl; 95% confidence intervals (CI) -31.27 to -2.35 mg/dl; P=0.02). A trend to improving total cholesterol (TC) reduction was found with Tai Chi (WMD -7.96 mg/dl; 95% CI -17.30 to 1.39 mg/dl; P=0.10). However, no difference was found in blood low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C). CONCLUSIONS: Tai Chi exercise lowered blood TG level with a trend to decrease blood TC level. Our data suggest that Tai Chi has the potential to implement meaningful blood lipid modification and serve as an adjunctive exercise modality. The relationship between Tai Chi exercise regimen and lipid profile change might have a scientific priority for future investigation.

SIRT3 in cardiovascular diseases: Emerging roles and therapeutic implications.

SIRT3 belongs to a highly conserved protein family of histone deacetylases and it is rich in mitochondria. As acetyl-modification is one of the important post-translational modifications that prevail in the mitochondria, it is not surprising that SIRT3 plays a key regulatory role in this organelle. SIRT3 has a wide range of substrates that are involved in the physiological and pathological processes of oxidative stress, ischemia-reperfusion injury, mitochondrial metabolism homeostasis and cellular death. These pathophysiological processes are considered as the underlying mechanisms of diseases like cardiac hypertrophy, myocardial infarction and heart failure, indicating the potential roles of SIRT3 in cardiovascular diseases. In this review, we will summarize the emerging roles and therapeutic implications of SIRT3 in cardiovascular diseases by providing an update on the latest understanding of its functions.

Regulatory T lymphocytes in myocardial infarction: A promising new therapeutic target.

Myocardial infarction (MI) is one of the leading causes of death especially in developed countries. Although the advent of early myocardial reperfusion therapy contributes to decreasing the mortality of patients with MI, cardiac ischemia-reperfusion injury and adverse remodeling during the repair process still remain the major factors impairing cardiac function and resulting in unsatisfactory prognosis. Excessive inflammation and immune responses play a crucial role during the whole process of MI. Regulatory T lymphocytes, characterized by immunosuppressive capacity, are associated with many immune-related diseases. Recent studies have proven a protective role of regulatory T cells in MI, which is mainly achieved by modulating inflammation and immune responses. In this review, we will summarize current knowledge of regulatory T lymphocytes, and highlight their roles in the onset of MI, ischemia-reperfusion injury, as well as post-infarct cardiac healing and remodeling.

Meta-analysis of C242T polymorphism in CYBA genes: risk of acute coronary syndrome is lower in Asians but not in Caucasians.

BACKGROUND: A lot of studies have demonstrated that C242T polymorphism in CYBA genes may play an important role in the pathological process of acute coronary syndrome (ACS). However, the results are not consistent. To further evaluate this debate, we performed a meta-analysis to determine the relationship between C242T polymorphism and ACS. METHODS AND RESULTS: We screened PubMed/MEDLINE, EBSCIO, and EMBASE research reports until Mar. 2014 and extracted data from 10 studies involving 6102 ACS patients and 8669 controls. Subgroup analysis by ethnicity documented a significant decreased risk of ACS for C242T polymorphism in the Asian population under allelic comparison (odd ratio (OR) 0.73; 95% confidence intervals (CI) 0.64-0.83), dominant model (OR 0.71; 95% CI 0.62-0.82), and homozygote comparison (OR 0.57; 95% CI 0.35-0.92). However, in the overall population and especially with Caucasians, no significant association was uncovered. Further meta-regression analysis revealed that the heterogeneity among studies was largely attributed to ethnicity. No publication bias was detected through a funnel plot and an Egger's linear regression test. CONCLUSIONS: Taken together, our results suggest that the C242T polymorphism might be a protective factor against developing ACS in the Asian population. Further researches will be needed to identify the confounding factors which modified the protective effect of T allele among Caucasians.

Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy.

BACKGROUND: Coprescribing of clopidogrel and other drugs is common. Available reviews have addressed the drug-drug interactions (DDIs) when clopidogrel is as an object drug, or focused on combination use of clopidogrel and a special class of drugs. Clinicians may still be ignorant of those DDIs when clopidogrel is a precipitant drug, the factors determining the degree of DDIs, and corresponding risk management. METHODS: A literature search was performed using PubMed, MEDLINE, Web of Science, and the Cochrane Library to analyze the pharmacokinetic DDIs of clopidogrel and new P2Y12 receptor inhibitors. RESULTS: Clopidogrel affects the pharmacokinetics of cerivastatin, repaglinide, ferulic acid, sibutramine, efavirenz, and omeprazole. Low efficacy of clopidogrel is anticipated in the presence of omeprazole, esomeprazole, morphine, grapefruit juice, scutellarin, fluoxetine, azole antifungals, calcium channel blockers, sulfonylureas, and ritonavir. Augmented antiplatelet effects are anticipated when clopidogrel is coprescribed with aspirin, curcumin, cyclosporin, St John's wort, rifampicin, and angiotensin-converting enzyme inhibitors. The factors determining the degree of DDIs with clopidogrel include genetic status (eg, cytochrome P540 [CYP]2B6*6, CYP2C19 polymorphism, CYP3A5*3, CYP3A4*1G, and CYP1A2-163C.A), species differences, and dose strength. The DDI risk does not exhibit a class effect, eg, the effects of clopidogrel on cerivastatin versus other statins, the effects of proton pump inhibitors on clopidogrel (omeprazole, esomeprazole versus pantoprazole, rabeprazole), the effects of rifampicin on clopidogrel versus ticagrelor and prasugrel, and the effects of calcium channel blockers on clopidogrel (amlodipine versus P-glycoprotein-inhibiting calcium channel blockers). The mechanism of the DDIs with clopidogrel involves modulating CYP enzymes (eg, CYP2B6, CYP2C8, CYP2C19, and CYP3A4), paraoxonase-1, hepatic carboxylesterase 1, P-glycoprotein, and organic anion transporter family member 1B1. CONCLUSION: Effective and safe clopidogrel combination therapy can be achieved by increasing the awareness of potential changes in efficacy and toxicity, rationally selecting alternatives, tailoring drug therapy based on genotype, checking the appropriateness of physician orders, and performing therapeutic monitoring.

Evaluation of the safety and efficacy of transcatheter aortic valve implantation in patients with a severe stenotic bicuspid aortic valve in a Chinese population.

OBJECTIVE: The purpose of this study is to evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with a severe stenotic bicuspid aortic valve (BAV) in a Chinese population. While several groups have reported the feasibility, efficacy, and safety of TAVI for patients with a BAV, worldwide experience of the technique is still limited, especially in China. METHODS: From March 2013 to November 2014, high surgical risk or inoperable patients with symptomatic severe aortic stenosis (AS) who had undergone TAVI at our institution were selected for inclusion in our study. RESULTS were compared between a BAV group and a tricuspid aortic valve (TAV) group. RESULTS: Forty patients were included in this study, 15 (37.5%) of whom were identified as having a BAV. In the BAV group, the aortic valve area was smaller ((0.47±0.13) vs. (0.59±0.14) cm(2)), the ascending aortic diameter was larger ((40.4±4.4) vs. (36.4±4.3) mm), and the concomitant aortic regurgitation was lower. No significant differences were found between the groups in the other baseline characteristics. No differences were observed either in the choice of access or valve size. The procedural success achieved in this study was 100%. There were no differences between groups in device success (86.7% vs. 88.0%), 30-d mortality (6.7% vs. 8.0%), or 30-d combined end point (13.3% vs. 12.0%). The incidences of new pacemaker implantation, paravalvular regurgitation and other complications, recovery of left ventricle ejection fraction and heart function were similar in both groups. CONCLUSIONS: Patients with a severely stenotic BAV can be treated with TAVI, and their condition after treatment should be similar to that of people with a TAV.

Torsade de pointes in a patient with complete atrioventricular block and pacemaker failure, misdiagnosed with epilepsy.

A case of torsade de pointes (TdP) with complete atrioventricular block and pacemaker failure that was misdiagnosed as epilepsy is presented herein. An 82-year-old female with recurrent seizure-like attacks showed epileptiform discharge during an electroencephalogram recording. A long QT interval and severe hypokalemia induced runs of TdP, which was related to pacemaker lead fracture, was detected during Holter recording and accompanied with episodes of seizures. After a DDD pacemaker with a new ventricular lead was replaced, there was no recurrence of any seizure-like attacks. Bradycardia-mediated TdP associated with complete atrioventricular block should not be missed in patients with recurrent seizure-like attacks even after pacemaker implantation.

Endothelial Progenitor Cells and In-stent Restenosis.

Coronary artery disease (CAD) is a significant global health problem, contributing to significant morbidity and mortality. Percutaneous coronary intervention (PCI) is an efficient therapy for treating CAD, but it carries the risk of iatrogenic endothelial injury, which contributes to vessel inflammation and induction of in-stent restenosis. Therefore, developing novel methods for enhancing re-endothelialization after PCI is highly needed. Endothelial progenitor cells (EPCs) can differentiate into mature endothelial cells, and cell therapy with EPC may offer a novel way for accelerating reendothelialization. In this review paper, we aimed to briefly describe EPCs and highlight their potential therapeutic roles in in-stent re-stenosis and endothelial injury.

[Status of glucose metabolism in Chinese essential hypertensive patients].

OBJECTIVE: To investigate glucose metabolism status and its relationship with blood pressure, obesity, renal function and cardio-cerebral vascular events in Chinese essential hypertensive patients. METHODS: Essential hypertensive patients without diabetic history were enrolled in this cross-sectional survey. All patients filled in questionnaires and received physical examination and laboratory tests. Oral glucose tolerance test (OGTT, fasting and 2 hours glucose level after drinking the 75 g glucose solution) was performed in patients who signed the informed consent. RESULTS: (1) The control rate of systolic BP was lower in patients with dysglycemia than in patients without dysglycemia (41.0% vs. 46.4%, P = 0.000). (2) The albuminuria detection rate and the abnormal rate of estimated glumerular filtration rate (eGFR) increased significantly with the deterioration of glucose metabolism. (3) Multifactor-analysis showed that abnormal waist circumference, decreased eGFR and presence of albuminuria were independent risk factors for abnormal glucose metabolism. Cardiovascular events was significantly higher in patients with abnormal glucose metabolism than patients with normal glucose metabolism. CONCLUSION: Abnormal glucose metabolism is common in Chinese essential hypertensive patients. When complicated with abnormal glucose metabolism, essential hypertensive patients had poor blood pressure control rate and were related to higher cardiovascular risk.

Outcomes research: science and action.

Outcomes research, which investigates the outcomes of health care practices, is intended to provide scientific evidence for clinical decision making and health care. This paper elucidates the goal and domains of outcomes research. Also it shows the potential and promise of outcomes research to provide a methodology to uncover what to do and how to do it, and enable the health care profession to achieve the right care, for the right patient, at the right time, the first time, every time, nothing more, and nothing less.

Interleukin-17 and acute coronary syndrome.

Inflammation plays an important role in atherosclerosis, which is also crucial for acute coronary syndrome (ACS). Recent studies have revealed that interleukin (IL)-17, which was regarded as a pro-inflammatory cytokine, has a dual function in the progress of ACS. In this review, we sum up both experimental and clinical studies on the relevance of IL-17 to atherosclerosis and its complications, and summarize the research progress on the effect of IL-17 on the atherosclerotic plaque stability and ACS onset. Although the studies are controversial and the mechanism remains unclear, we highlight the knowledge of the role of IL-17 in ACS and elucidate its potential mechanism.

Cathepsin S-mediated fibroblast trans-differentiation contributes to left ventricular remodelling after myocardial infarction.

BACKGROUND: Extracellular matrix (ECM) turnover plays an important role in left ventricular (LV) remodelling following myocardial infarction (MI). Cysteinyl cathepsins contribute to ECM catabolism in arterial diseases, suggesting their participation in post-MI remodelling. METHODS AND RESULTS: Left anterior descending artery ligation-induced MI in mice showed increased expression and activity of cathepsin S (CatS). Administration of a non-selective cathepsin inhibitor, E64d, aggravated LV dysfunction at 7 and 28 days post-MI. Mechanistic studies showed that E64d increased post-MI inflammatory cell accumulation and cytokine expression, but did not affect apoptosis or angiogenesis in infarcted myocardium. Furthermore, E64d suppressed TGF-ß1-induced Smad2 and Smad3 activation and expression of fibronectin extra domain A (ED-A), an alternatively spliced fibronectin variant, and subsequently prevented cardiac fibroblast trans-differentiation into myofibroblast, which contributed to post-MI collagen and fibronectin synthesis and deposition. Consistently, selective inhibition or genetically determined deficiency of CatS also reduced myocardial Smad2 and Smad3 activation and ED-A fibronectin expression, thus suppressing fibroblast trans-differentiation and resulting in adverse collagen turnover and impaired cardiac function-recapitulating the findings in mice treated with E64d. CONCLUSION: Along with its established activities in ECM degradation, CatS plays novel roles in TGF-ß1 signalling, myofibroblast trans-differentiation, and ECM protein synthesis, thereby regulating scar formation in the infarcted myocardium and preserving LV function after experimental MI.