Integrated microRNA–mRNA analysis of coronary artery disease

Although patients with coronary artery disease (CAD) have a high mortality rate, the pathogenesis of CAD is still poorly understood. The purpose of this study was to explore the underlying molecular mechanisms and potential target molecules for CAD. The platelet miRNA (GSE28858) and blood mRNA (GSE42148) expression profiles of patients with CAD and healthy controls were downloaded from Gene Expression Omnibus. Differentially expressed miRNAs and genes (DEGs) were identified by significant analysis of microarray algorithm after data preprocessing. Furthermore, the miRNA-target gene regulatory network was constructed based on miRecords database. The spearman correlation coefficients (ρ) between miRNAs and their target genes were calculated. Six up- (miR-340, miR-545, miR-451, miR454-5p, miR-624 and miR-585) and four down-regulated (miR-199a, miR-17-3p, miR-154 and miR-339) miRNAs were screened. Total 295 target genes of miR-545, miR-451, miR-585 and miR-154 were predicted. Among these 295 target genes, 7 genes were DEGs. Further analysis showed miR-545-TFEC and miR-585-SPOCK1 were highly positively correlated (ρ = 0.808091264; ρ = 0.874680776) in CAD samples. Therefore, differentially expressed miRNAs might participate in the pathogenesis of CAD by regulating their target genes.     

Coronary artery surgery: are women discriminated against?

OBJECTIVE--To determine whether the sex differences in access to cardiac surgery observed in the United States exist in the United Kingdom. DESIGN--Retrospective analysis of routinely collected data. SETTING--South West Thames and North West Thames regional health authorities. SUBJECTS--8564 patients discharged from hospital with a principal diagnosis of coronary heart disease in 1987-8 in South West Thames region and 15243 discharges in North West Thames region in 1990-1. MAIN OUTCOME MEASURES--Performance of angiography or coronary artery bypass surgery. RESULTS--In all age groups and among patients with a principal diagnosis of either angina or chronic ischaemia men were significantly more likely than women to undergo revascularisation in both regions. Using multiple logistic regression to control for potential clinical and demographic confounders, the male to female odds ratio for revascularisation among all cases was 1.59 (95% confidence interval 1.25 to 2.03) in South West Thames region and 1.47 (1.32 to 1.63) in North West Thames region. CONCLUSION--There appears to be a systematic difference in the treatment received by men and women in the United Kingdom. The reasons for this are uncertain.     

Choose your fate: artery, vein or lymphatic vessel?

The specification of cell fate is integral to embryonic development. Recent research has identified several molecules that are involved in the development of the embryonic vasculature. Their combined actions are required for the specification and development of the arteries, veins and lymphatic vessels; vascular networks that are vital for embryonic and adult survival, and whose malfunction causes major pathological disorders. Recent discoveries have impacted our understanding of the embryonic origins of arterial, venous and lymphatic endothelial cells and the signals that mediate their navigation into mature, functional circulatory systems.     

Coronary artery disease: Are men and women created equal?

Background: Ischemic heart disease in women is a difficult issue in cardiovascular medicine, mainly because of our lack of understanding of the early-stage mechanisms and symptoms. A better and earlier understanding of the pathophysiology of coronary artery disease (CAD) in women will enable us to detect ischemic heart disease earlier and prevent adverse clinical outcomes.Objectives: The aims of this article were to describe the phenomenon of ischemic heart disease in women, increase awareness of the difference between men and women in relation to ischemic heart disease, improve our understanding of the mechanisms that cause this difference, and identify new approaches for better and earlier detection and treatment of CAD in women.Methods: We conducted a search of the PubMed database for double-blind studies on the mechanistic pathways of CAD in women published in English within the past 10 years and epidemiologic studies published since 1970. Search terms included women and coronary artery disease and ischemic heart disease in women.Results: The literature search revealed 30 peer-reviewed articles pertaining to this issue. The incidence of CAD was markedly lower in women <60 years of age than in older women. After 60 years of age, the rate of CAD increased and reached the rate seen among men by the 8th decade of life. The gender difference in atherosclerosis in the coronary tree was particularly large in patients <55 years of age and remained large at older ages. The gender difference in the coronary bed was strikingly larger than in other vascular beds. Intensive risk-factor modification had a similar effect on plaque progression in both men and women. Coronary endothelial dysfunction appeared to be related to cardiovascular morbidity and mortality in women as well as in men, and because endothelial dysfunction could be modified, it appeared that the prognosis could be improved by appropriate management. A strong association was found between body mass index (BMI) and metabolic status, but only the metabolic syndrome was associated with CAD. Physical activity was independently associated with fewer risk factors, less CAD, and fewer adverse events in women; however, obesity was not associated with these outcomes.Conclusions: Results of the identified studies suggest that reduction of risk factors is a common approach to fighting heart disease in both sexes. It appears that for women, weight and BMI are not as important as previously thought, but physical exercise and fitness are very important and can change risk factors and clinical outcomes more than any other known intervention. Data suggest that global inflammation may play an important role in women and may predict cardiovascular outcome in women much better than the traditional risk factors that have been used and proved for men.     

Coronary artery bypass grafting: how much does it cost?

OBJECTIVE: To calculate the cost of coronary artery bypass grafting (CABG) and to compare it with the costs determined in two previous Canadian studies. DESIGN: Retrospective cost-analysis study. SETTING: A tertiary care referral hospital. PATIENTS: Fifty patients who had undergone successful triple and quadruple CABG between Jan. 3 and 30, 1989. MAIN RESULTS: The cost of CABG per patient varied from $10,982 to $33,676 (mean $14,328) (in 1988 Canadian dollars). The cost tended to increase with age and number of vessels grafted. Compared with the patients in the two previous Canadian studies our patients were older, had more vessels grafted and cost more to treat, even after the total hospital costs were adjusted for inflation. CONCLUSIONS: The population undergoing CABG is changing: it is older and has more diseased vessels. These changes have had a significant impact on the cost of CABG. Further study is required to determine the outcome and benefit of CABG in this group of patients.     

Case–control association study of polymorphisms in the angiotensinogen and angiotensin-converting enzyme genes and coronary artery disease and systemic artery hypertension in African-Brazilians and Caucasian-Brazilians

The rennin–angiotensin–aldosterone system (RAAS) is a critical pathway in regulating blood pressure and salt/water homeostasis, possessing an intimate relationship with the development of systemic artery hypertension (SAH). Once hypertension is considered a risk factor for coronary artery disease (CAD), the RAAS is also related to this pathology. This investigation aimed to analyse if the frequencies of AGT M235T (rs699) and ACE I/D (rs4646994) polymorphisms are associated with CAD and SAH in African-Brazilians and Caucasian-Brazilians. In this study we analysed 714 subjects who underwent coronary angiography to detect obstructive lesions and CAD, as well as blood pressure measurement and SAH, grouped according to ethnicity: 266 African-Brazilians and 448 Caucasian-Brazilians. Among CAD and SAH cases and controls, the genotype and allele frequencies of ACE I/D polymorphism were similar in both ethnic groups. The AGT 235TT genotype and 235T allele frequencies were higher in SAH cases (32%, 54.7%) versus controls in Caucasian-Brazilians (19.8%, 46.4%; P= 0.038, P= 0.031, respectively). The AGT 235TT (OR = 1.8; P= 0.028) demonstrated to be an independent factor risk in a multivariate logistic regression increasing SAH risk in Caucasians but not in African-Brazilians. In summary, AGT M235T polymorphism was associated with SAH risk in Caucasian-Brazilians, and no association was detected with CAD. No association was also observed in ACE I/D polymorphism either in CAD or SAH in African-Brazilians and Caucasian-Brazilians.     

Intraoperative radial nerve injury during coronary artery surgery – report of two cases

Background

Peripheral nerve injury and brachial plexopathy are known, though rare complications of coronary artery surgery. The ulnar nerve is most frequently affected, whereas radial nerve lesions are much less common accounting for only 3% of such intraoperative injuries.

Case presentations

Two 52- and 50-year-old men underwent coronary artery surgery. On the first postoperative day they both complained of wrist drop on the left. Neurological examination revealed a paresis of the wrist and finger extensor muscles (0/5), and the brachioradialis (4/5) with hypoaesthesia on the radial aspect of the dorsum of the left hand. Both biceps and triceps reflexes were normoactive, whereas the brachioradialis reflex was diminished on the left. Muscles innervated from the median and ulnar nerve, as well as all muscles above the elbow were unaffected. Electrophysiological studies were performed 3 weeks later, when muscle power of the affected muscles had already begun to improve. Nerve conduction studies and needle electromyography revealed a partial conduction block of the radial nerve along the spiral groove, motor axonal loss distal to the site of the lesion and moderate impairment in recruitment with fibrillation potentials in radial innervated muscles below the elbow and normal findings in triceps and deltoid. Electrophysiology data pointed towards a radial nerve injury in the spiral groove. We assume external compression as the causative factor. The only apparatus attached to the patients' left upper arm was the sternal retractor, used for dissection of the internal mammary artery. Both patients were overweight and lying on the operating table for a considerable time might have caused the compression of their left upper arm on the self retractor's supporting column which was fixed to the table rail 5 cm above the left elbow joint, in the site where the radial nerve is directly apposed to the humerus.

Conclusion

Although very uncommon, external compression due to the use of a self retractor during coronary artery surgery can affect – especially in obese subjects – the radial nerve within the spiral groove leading to paresis and should therefore be included in the list of possible mechanisms of radial nerve injury.     

Simvastatin has beneficial effect on pulmonary artery hypertension by inhibiting NF-��B expression

Altered cellular mitochondrial membrane potential (MMP) has been implicated in the increased insulin resistance and the risk for diabetes. Hyperketonemia is increasingly being identified in type 2 diabetic patients in addition to those with type 1 diabetes. No previous study has examined the effect of hyperketonemia and trivalent chromium on cellular mitochondrial membrane potential (MMP) in any cell type. Using a U937 monocyte cell culture model, this study examined the hypothesis that hyperketonemia decreases and trivalent chromium normalizes the cellular MMP level. Cells were cultured with control and ketone bodies [acetoacetate (AA), β-hydroxybutyrate (BHB)] in the absence or the presence (0.5-100 μM) of Cr(3+) at 37°C for 24 h. The MMP was determined using DiOC6 and flow cytometry. The results show a significant decrease in MMP in cells treated with AA, but not in the cells treated with BHB. The effect of AA on cellular MMP was prevented in chromium (III)-pretreated cells. Thus, hyperketonemia decreases the MMP, and supplementation with chromium (III) normalizes altered MMP, which may play a role in the improvement in glucose metabolism seen after chromium (III) supplementation in some studies with diabetic animals and patients.     

In-vivo three-dimensional carpal bone kinematics during flexion–extension and radio–ulnar deviation of the wrist: Dynamic motion versus step-wise static wrist positions

An in-vivo approach to the measurement of three-dimensional motion patterns of carpal bones in the wrist may have future diagnostic applications, particularly for ligament injuries of the wrist. Static methods to measure carpal kinematics in-vivo only provide an approximation of the true kinematics of the carpal bones. This study is aimed at finding the difference between dynamically and statically acquired carpal kinematics.For eight healthy subjects, static and a dynamic measurements of the carpal kinematics were performed for a flexion–extension and a radio–ulnar deviation movement. Dynamic scans were acquired by using a four-dimensional X-ray imaging system during an imposed cyclic motion. To assess static kinematics of the wrists, three-dimensional rotational X-ray scans were acquired during step-wise flexion–extension and radio–ulnar deviation. The helical axis rotations and the rotation components. i.e. flexion–extension, radio–ulnar deviation and pro–supination were the primary parameters. Linear mixed model statistical analysis was used to determine the significance of the difference between the dynamically and statically acquired rotations of the carpal bones.Small and in most cases negligible differences were observed between the dynamic motion and the step-wise static motion of the carpal bones. The conclusion is that in the case of individuals without any pathology of the wrist, carpal kinematics can be studied either dynamically or statically. Further research is required to investigate the dynamic in-vivo carpal kinematics in patients with dynamic wrist problems.     

Who will be active? Predicting exercise stage transitions after hospitalization for coronary artery disease

We describe transitions between exercise stages of change in people with coronary artery disease (CAD) over a 6-month period following a CAD-related hospitalization and evaluate constructs from Protection Motivation Theory, Theory of Planned Behavior, Social Cognitive Theory, the Ecological Model, and participation in cardiac rehabilitation as correlates of stage transition. Seven hundred eighty-two adults hospitalized with CAD were recruited and administered a baseline survey including assessments of theory-based constructs and exercise stage of change. Mailed surveys were used to gather information concerning exercise stage of change and participation in cardiac rehabilitation 6 months later. Progression from pre-action stages between baseline and 6 month follow-up was associated with greater perceived efficacy of exercise to reduce risk of future disease, fewer barriers to exercise, more access to home exercise equipment, and participation in cardiac rehabilitation. Regression from already active stages between baseline and 6 month follow-up was associated with increased perceived susceptibility to a future CAD-related event, fewer intentions to exercise, lower self-efficacy, and more barriers to exercise.     

Changes in pulmonary Cu−Zn contents in superior mesenteric artery occlusion shock of rabbit

Contents of Cu and Zn of into-pulmonary blood (IPB), out-pulmonary blood (OPB), Lung tissue, and supernatant and macrophages of Lung Lavage were determined in superior mesenteric artery occlusion (SMAO) shock of rabbits. Zn of pulmonary tissue was 11.42 +/- 0.60 and 14.52 +/- 1.78 (micrograms/g wet wt) in SMAO shock and control groups, respectively. Content of Zn was found to be lower, Cu was not changed, and Cu/Zn ratio increased in lung tissue in SMAO shock. Contents of Cu and Zn in other samples were not changed. The results suggest that lower Zn in lung tissue related to acute lung injury.     

LOX-1, a new marker of risk and prognosis in coronary artery disease?

The development of atherosclerosis is caused by the accumulation of lipid, inflammatory cytokine production, and the large amount of inflammatory cells in the arterial wall. It is now established that the presence of oxidized low-density lipoproteins (ox-LDL) has an important role in the pathogenesis of the disease. There are many scavenger receptors for ox-LDL, among which LOX-1 seems to be important for the induction of endothelial dysfunction and the other subsequent events that lead to the formation of atheromatous plaque. Our findings indicate the presence of a regulatory role induced by the presence of ox-LDL on LOX-1 through the amplification of IL-6 synthesis. This mechanism contributes to the upregulation of the ORL-1 gene expression in presence of risk factors. Many authors have shown the possibility to use LOX-1 as a good marker for the diagnosis and prognosis of coronary artery disease because it is easy to measure and more sensitive than other markers commonly used in the routine of laboratory medicine.