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Marjan Jahangiri

Publications and source records attributed to Marjan Jahangiri.

At least 19 recordsLinked to original sources

Characterisation of progenitor cells in human atherosclerotic vessels.

Recent data from animal models has demonstrated that both endothelial and smooth muscle progenitor cells contribute to the development of atherosclerosis. However, no data exists concerning the presence of progenitor cells in human atherosclerotic vessels. In the present study, a range of normal and atherosclerotic human arteries were collected from patients undergoing coronary artery bypass surgery. Segments of internal mammary artery (normal controls), and segments of proximal ascending aorta with visible fatty streak were analysed. Immunofluorescence was used to detect a panel of progenitor cell markers. A small number of progenitor cells were identified within neointimal lesions and the adventitia with variable expression of CD34, stem cell antigen (Sca-1), c-kit and VEGF receptor 2 (VEGFR2) markers, but no CD133 expression. On average there was a two- to three-fold increase in progenitor cell number in the adventitia of atherosclerotic vessels compared with normal controls, with a significant difference (p<0.05) in the frequency of cells expressing VEGFR2. Thus, we have provided the first evidence that vascular progenitor cells exist within atherosclerotic lesions, and identified an increased number of progenitor cells in the adventitia of human atherosclerotic vessels. These cells might be a source for smooth muscle cells (SMCs), macrophages and endothelial cells (ECs) that form atherosclerotic lesions.

AC133 Antigen↗

Post-stenotic aortic dilatation.

Aortic stenosis is the most common valvular heart disease affecting up to 4% of the elderly population. It can be associated with dilatation of the ascending aorta and subsequent dissection. Post-stenotic dilatation is seen in patients with AS and/or aortic regurgitation, patients with a haemodynamically normal bicuspid aortic valve and following aortic valve replacement. Controversy exists as to whether to replace the aortic root and ascending aorta at the time of aortic valve replacement, an operation that potentially carries a higher morbidity and mortality. The aetiology of post-stenotic aortic dilatation remains controversial. It may be due to haemodynamic factors caused by a stenotic valve, involving high velocity and turbulent flow downstream of the stenosis, or due to intrinsic pathology of the aortic wall. This may involve an abnormality in the process of extracellular matrix remodelling in the aortic wall including inadequate synthesis, degradation and transport of extracellular matrix proteins. This article reviews the aetiology, pathology and management of patients with post-stenotic aortic dilatation.

Animals↗

Current strategies in the management of atrial fibrillation.

Treatment of atrial fibrillation (AF) has been undergoing significant changes recently. This is due partly to different mechanisms proposed for persistent and permanent AF and partly due to the introduction of energy-based techniques, providing less invasive procedures. This article aims to review the mechanisms of AF leading to the changes in clinical practice and to review the results of surgery, energy-based, and percutaneous techniques. It is difficult to compare and contrast the results of reported series in the literature due to different definitions of AF; freedom from and recurrence of it. Furthermore, in most series it is difficult to distinguish results of surgery for lone AF and AF associated with valvular heart disease and coronary artery disease.

Atrial Fibrillation↗

Health-related quality of life outcome after on-pump versus off-pump coronary artery bypass graft surgery: a prospective randomized study.

BACKGROUND: The clinical benefit of off-pump coronary artery bypass graft surgery over on-pump surgery is a matter of controversy. The aim of this study was to assess quality of life in patients after on-pump and off-pump coronary artery bypass graft surgery, and compare the data with an age-matched and sex-matched standard population. METHODS: Two hundred twelve patients admitted for elective coronary artery bypass graft surgery were randomized to on-pump (n = 104) and off-pump (n = 108) surgery. Quality-of-life assessments were made 6 and 18 months postoperatively using the standard form of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36, version 2). The questionnaire yields eight subscores of functional health and well being. The eight SF-36 raw scores were standardized using means and standard deviations from a random sample of adults in Great Britain. Mean on-pump and off-pump SF-36 scores were compared using two-sample Student's t tests. RESULTS: Questionnaires were completed for 72% (154 of 212) and 46% (98 of 212) of patients at the 6- and 18-month follow-up, respectively. There were no significant differences between on-pump and off-pump patients in any of the eight subscales at both stages. Fifty-six (72%) on-pump and 59 (75%) off-pump patients reported a better health status compared with the 6-month period before surgery (not significant). CONCLUSIONS: Patients who have undergone off-pump coronary artery bypass graft surgery have a similar quality of life to on-pump patients at 6 and 18 months after surgery. For both groups, the majority of patients reported improved health after coronary artery bypass graft surgery compared with their preoperative status.

Aged↗

Anti-heat shock protein 60 autoantibodies induce atherosclerosis in apolipoprotein E-deficient mice via endothelial damage.

BACKGROUND: Accumulating evidence established a positive association of anti-heat shock protein 60 (HSP60) autoantibodies and the presence of atherosclerosis in humans. However, whether these autoantibodies play a causal role in the development of atherosclerosis is unknown. METHODS AND RESULTS: In the present study, anti-HSP60 autoantibodies from blood of patients with coronary heart disease were isolated by affinity chromatography and injected into the tail vein of apolipoprotein E-deficient mice. Atherosclerotic lesions in aortas were significantly increased 8 weeks after injection. Furthermore, administration of a specific mouse monoclonal antibody (II-13) recognizing amino acid residues 288 to 366 of HSP60 effectively induced atherosclerotic lesions in apolipoprotein E-deficient mice. II-13 injection resulted in endothelial cell damage, followed by increased leukocyte attachment and accumulation of macrophages and smooth muscle cells in lesions. Interestingly, II-13-induced atherosclerosis was blocked by pretreatment of animals with F(ab)2 segments derived from the antibody, but not mouse IgG F(ab)2. CONCLUSIONS: Autoantibodies recognizing amino acid residues 288 to 366 of HSP60 induce atherosclerosis via the mechanisms of autoimmune reactions to HSP60 expressed on arterial endothelial cells, which can be prevented by F(ab)2 segments derived from these antibodies.

Animals↗

Association of high intracellular, but not serum, heat shock protein 70 with postoperative atrial fibrillation.

BACKGROUND: Atrial fibrillation is a common arrhythmia, after cardiac surgery. Reperfusion injury and inflammation associated with cardiac surgery are thought to be involved in its pathogenesis. We hypothesized that cytoprotective effects associated with heat shock protein 70 (HSP70) could counteract these proarrhythmic insults. We therefore set out to examine the influence of heat shock protein 70 on the incidence of postoperative atrial fibrillation. METHODS: We prospectively recruited 80 patients undergoing elective coronary artery bypass surgery. Blood samples were collected preoperatively. Right atrial tissue was obtained at surgery. Incidence of postoperative atrial fibrillation and its duration were noted. Using a nested case-control design, 15 patients who developed atrial fibrillation were matched for operative procedure, age, sex, and beta-blocker usage, with 15 controls from the remaining patients. Atrial heat shock protein 70 was subsequently quantified by immunohistochemistry. Serum heat shock protein was measured using enzyme-linked immunosorbent assay and high sensitivity C-reactive protein was determined by immunoturbidometric assay. RESULTS: Intracellular HSP70 level was significantly higher in patients who did not develop atrial fibrillation (35 +/- 13 vs 19 +/- 15; p = 0.006). Atrial HSP70 level negatively correlated with atrial fibrillation; independent of other risk factors (odds ratio = 0.90; 95% confidence interval 0.84 to 0.99, p = 0.02). Serum HSP70 levels were similar in both groups (p = 0.81) and did not correlate with intracellular levels (p = 0.38). Preoperative C-reactive protein levels were similar in both groups (p = 0.93). CONCLUSIONS: Intracellular, but not serum, HSP70 level is negatively correlated with postoperative atrial fibrillation. This suggests a cardioprotective and an antiarrhythmic role for intracellular HSP70.

Aged↗

Association of anti-heat shock protein 65 antibodies with development of postoperative atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a frequently encountered arrhythmia after cardiac surgery, but its underlying mechanisms are still unclear. We hypothesize that autoimmune and inflammatory responses against heat shock protein 65 (HSP65) may be involved and hence examined the relationship between HSP65 autoantibodies and occurrence of postoperative AF. METHODS AND RESULTS: A prospective study of 329 patients undergoing elective primary CABG was undertaken. Cardiovascular risk factors, ECG characteristics, medications, and intraoperative and postoperative features were documented. Anti-HSP65 antibodies and C-reactive protein levels were measured in all preoperative blood samples with ELISA. Postoperative AF was defined as the characteristic arrhythmia, lasting for at least 15 minutes and confirmed on 12-lead ECG and occurring within the first postoperative week. This occurred in 62 patients (19%). In univariate analysis, HSP65 antibodies were significantly higher in patients with postoperative AF (P=0.02). History of previous myocardial infarction, duration of bypass, number of distal anastomosis, and duration of ventilation were also associated with AF (P<0.05), but C-reactive protein levels were not (P=0.13). Multivariate analysis confirmed the positive association of HSP65 antibodies with postoperative AF (OR, 1.41; P=0.04) independent of age, sex, other cardiovascular risk factors, severity of coronary artery disease, duration of ventilation, duration of bypass, and left ventricular function. CONCLUSIONS: We report a novel association between anti-HSP65 antibodies and occurrence of postoperative AF, indicating a possible role for antibody-mediated immune response in its pathogenesis.

Aged↗

The role of coronary angiography in acute type A aortic dissection.

OBJECTIVES: In recent years, non-invasive methods have replaced angiography in the diagnosis of aortic dissection. Angiography maybe used to evaluate coexisting coronary artery disease (CAD), which can delay surgery and increase the risk of rupture. We set out to examine the role of angiography in acute aortic dissection. METHODS: A retrospective analysis of patients who underwent repair of acute aortic dissection between January 1992 and June 2002 was conducted. The effect of angiography on the need for concomitant coronary artery surgery (CABG), delay to surgery and outcome were analysed. RESULTS: Seventy-four patients were identified. Initial diagnosis was established by non-invasive techniques. Twenty-three patients (31%) underwent angiography (Group I) in three this was unsuccessful. Three in Group I and four in the non-angiography group (Group II, n=51) had history of angina. One patient in Group I underwent concomitant CABG compared to seven in Group II. The patient who underwent CABG in Group I; and four out of seven in Group II died (NS). Patients who underwent concomitant CABG had a significantly higher mortality rate (P=0.04). Mortality in Group I was 35% (n=8) and in Group II was 29% (n=15) (NS). Mortality rate was also significantly higher in patients who presented with syncope (P=0.01) or hypotension (P=0.04). Median transfer time from arrival at our centre to the operating room was 5 h in Group I and 1.5 h in Group II (P<0.001). Mortality rate was higher in patients who took longer to transfer to the operating room, but this did not reach statistical significance. CONCLUSIONS: We have shown that coronary angiography did not affect the occurrence of CABG and was not associated with improved hospital survival. Furthermore, there is a considerable delay to surgery caused by angiography. Therefore in this setting coronary angiography is not recommended.

Acute Disease↗

S100 protein and its relation to cerebral microemboli in on-pump and off-pump coronary artery bypass surgery.

OBJECTIVES: S100 protein has been used as a marker for cerebral injury. Studies have reported lower levels in off-pump coronary artery surgery (CABG) compared to on-pump surgery. However, most of these are flawed as S100 from extracerebral sources was included (e.g. blood from cardiotomy suckers). Microemboli (high-intensity transient signals or HITS) during CABG have been implicated as a cause of postoperative neurocognitive dysfunction. The aim of this study was to compare the number of HITS during on-pump and off-pump CABG, measure S100 accurately by excluding extracerebral sources, and assess whether any changes in S100 were related to HITS. METHODS: Thirty-five patients admitted for CABG were randomised to on-pump (n=20) or off-pump (n=15) surgery. Bilateral transcranial Doppler ultrasonography was performed on the middle cerebral artery to detect HITS. S100 was measured preoperatively, at termination of bypass in on-pump surgery, at completion of anastomoses in off-pump surgery, and 48 h postoperatively. A cell saver was used instead of cardiotomy suction in the on-pump group in order to limit extracerebral contamination of the S100 assay. RESULTS: The number of HITS was 2016+/-1897 during on-pump and 16+/-21 during off-pump surgery (P<0.0001). In on-pump surgery S100 increased from 0.05+/-0.03 to 0.50+/-0.28 microg/l (P<0.0001) at termination of bypass. In off-pump surgery S100 increased from 0.08+/-0.05 to 0.35+/-0.20 microg/l (P<0.0001) at completion of anastomoses. The mean intraoperative S100 in the on-pump group was 1.6 times greater compared to that in the off-pump group (95% CI 0.88-2.8; P=0.01). There was no evidence of a relationship between S100 and HITS in both groups. By 48 h S100 decreased to 0.22+/-0.14 microg/l in the on-pump and 0.21+/-0.09 microg/l in the off-pump group (P<0.0001, compared to the preoperative value). CONCLUSIONS: We have demonstrated a significantly higher number of cerebral microemboli in patients undergoing on-pump compared to off-pump CABG. By limiting contamination from extracerebral sources, we have shown S100 beta levels during on-pump CABG one and a half times greater than that in off-pump, although this did not reach statistical significance. In addition, we have shown no correlation between S100 beta and the total microemboli count, possibly because of the small numbers in this study.

Aged↗

Autoimmunity to heat shock proteins in atherosclerosis.

Current evidence lends increasing support to immunoinflammatory mechanisms as one of the prime pathogenic processes involved in the development and progression of atherosclerosis. It has been observed that most human beings have cellular and humoral reactions against microbial heat shock protein (HSP). Autoantibody levels against HSPs are significantly increased in patients with atherosclerosis and T lymphocytes specifically responding to HSPs have been demonstrated within atherosclerotic plaques. Most of the known risk factors for atherosclerosis, viz. oxidized low-density lipoprotein, hypertension, infections and oxidative stress, evoke increased expression of HSPs in endothelial cells, smooth muscle cells and macrophages, the main cellular constituents of atherosclerotic plaques. Evolutionary conservation has resulted in a high degree of sequence homology between microbial and human HSPs and hence the immune reactions against microbial HSPs carry a risk of being misdirected towards human HSPs expressed in the stressed cells of the blood vessels. HSPs and anti-HSP antibodies have been shown to elicit production of pro-inflammatory cytokines by macrophages and adhesion molecules by endothelial cells in various in vitro and animal model studies. These autoimmune reactions to HSPs expressed in the vascular tissue can contribute to both initiation and perpetuation of atherosclerosis.

Animals↗

Management of patients undergoing coronary artery bypass graft surgery with mild to moderate aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: The management of patients undergoing coronary artery bypass graft (CABG) surgery with mild to moderate aortic stenosis (AS) remains controversial. The study aim was to examine the outcome in patients with mild to moderate AS undergoing CABG. METHODS: A retrospective analysis was carried out of 200 patients with coronary artery disease requiring CABG and with a peak AS gradient < 40 mmHg measured by Doppler echocardiography, between 1990 and 2000. Among patients, 154 underwent isolated CABG (group A) and 46 CABG + aortic valve replacement (AVR) (group B). RESULTS: Mortality was 2.6% (n = 4) in group A and 6.5% (n = 3) in group B (p = NS). The median AS gradients were 34 and 40 mmHg, respectively. Thirty patients (20%) in group A were in NYHA class III-IV compared to 20 (44%) in group B (p = 0.002). There was no significant difference in postoperative complications. The mean intensive care unit stay was 2.3 and 2.2 days, respectively (p = NS); median postoperative stay was 6 and 8 days, respectively (p = 0.02). During the median follow up period of 4.2 years no patient in group A required AVR. Nine late deaths occurred in group B, none of which was cardiac-related. CONCLUSION: Morbidity and mortality in patients who underwent combined surgery was comparable with that in patients who had isolated CABG. However, none of the patients who underwent only CABG required AVR during the follow up period. It is concluded that patients with mild AS at the time of CABG should not undergo AVR. It is possible that a cut-off AS gradient > 40 mmHg should be considered for combined surgery.

Aged↗