Rumi J. Jaumdally

The effect of melatonin on plasma markers of inflammation and on expression of nuclear factor-kappa beta in acetic acid-induced colitis in the rat.

Background and AimsMelatonin may be involved in gastrointestinal tract physiology and could affect inflammation-related gastrointestinal disorders. Rat models of ulcerative colitis imply melatonin is beneficial. To determine potential pathophysiological mechanisms, we assessed colonic nuclear factor-kappa beta expression and measured serum levels of pentraxin-3, lipid peroxides, and total thiols in an acetic acid model of this disease.Materials and MethodsThirty rats were divided into five groups: a control group, an acetic acid-induced colitis group, a group treated with melatonin before colitis induction, a group treated short-term after colitis induction, and a group treated long-term after colitis induction. After four weeks, blood samples were taken for measurement of pentraxin-3, lipid peroxide, and total thiols. Sections of the colon were taken for histopathological examination and immunohistochemical detection of nuclear factor-kappa beta expression.ResultsMelatonin administration reduced nuclear factor-kappa beta immunohistochemical expression, reduced serum levels of lipid peroxide and pentraxin-3, and maintained serum levels of total thiols. However, in long-term treatment the protective effect of melatonin was not as marked.ConclusionMelatonin is effective in prevention and short-term treatment of the inflammatory process in acetic-acid induced colitis whereas the benefit of long-term treatment is unclear. Benefit may be linked to protection mechanisms against inflammatory processes by inhibiting the nuclear factor-kappa beta and conserving endogenous antioxidant reserves of total thiols, thus reducing the level of colonic damage possibly caused by lipid peroxides.

Anger rumination, social support, and cardiac symptoms in patients undergoing angiography

OBJECTIVES Socially isolated individuals report more cardiac symptoms, suffer increased cardiovascular morbidity and mortality, and experience higher levels of stress and anxiety than those with more effective support resources. However, the complex interactions of psychosocial factors implicated in the disease process remain to be fully elucidated. We sought to explore these relationships, with the addition of a novel psychosocial variable, anger rumination, which could be associated with increased cardiovascular risk. DESIGN We examined the association of psychological stress, social support, and anger rumination, with surgical anxiety, self-reported cardiac symptoms, and angiographically documented coronary artery disease, using a correlational ex post facto design. METHODS One hundred and one patients scheduled for elective coronary angiography completed questionnaires during the week prior to angiography. Disease severity was objectively assessed using the Gensini scoring system. RESULTS Self-reported cardiac symptom severity was significantly correlated with higher perceived stress, less social support, and higher anger rumination, but none of the psychosocial variables predicted Gensini score. Social support partially mediated the relationship between anger rumination and surgical anxiety. Perceived stress mediated the relationship between anger rumination and cardiac symptoms. CONCLUSIONS For patients awaiting angiography, stress, and lack of social support are important predictors of self-reported cardiac symptoms, irrespective of actual disease severity. Intervention could focus on reducing perceived stress by encouraging reappraisal and a support seeking, rather than a ruminative, anger coping style.

Plasma haemoxygenase-1 in coronary artery disease. A comparison with angiogenin, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 and vascular endothelial growth factor.

It was the aim of this study to determine plasma haemoxygenase-1 (HO-1) across the spectrum of health, angina but normal coronary arteries (NCA), stable coronary artery disease (CAD), and acute coronary syndromes (ACS), and relationships with angiogenin, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1, and vascular endothelial growth factor. Plasma markers were measured (ELISA) in peripheral venous citrated plasma from 50 healthy subjects, 30 with NCA, 70 with stable CAD and 24 with an ACS, and from patients aortic root, coronary ostium, coronary sinus and femoral artery. Human umbilical vein endothelial cells (HUVECs) were cultured with or without tumour necrosis factor (TNF), and platelets were probed. HO-1 was raised in stable CAD (p<0.05) and increased further in ACS (p<0.01) compared to healthy controls and NCA. HO-1 correlated only with MMP-9, and then only in the healthy controls. There were no major differences from cardiac or peripheral sites. HO-1 was present in HUVECs and 24-hour HUVEC supernatants but release was abolished by TNF. Platelets had no HO-1. In conclusion, HO-1 is raised in stable CAD and ACS and may arise from the endothelium but not the platelet. This may have implications for our understanding of the pathophysiology of CAD and its acute presentation as ACS.

Eosinophil count predicts mortality following percutaneous coronary intervention.

INTRODUCTION Several inflammatory markers have been shown to be independent predictors for both the development of clinically significant atherosclerosis and for adverse outcome in patients with symptomatic coronary artery disease (CAD). We investigated the prognostic role of eosinophil count in low to intermediate risk patients with CAD. METHODS We studied 909 patients admitted for elective or urgent percutaneous coronary intervention (PCI) from April 2002 to December 2004, and measured pre-procedural total and differential white blood cell (WBC) counts. Inter-tertile WBC differences in short (6months) and long term (up to 74months) mortality were analysed after adjusting for differences in baseline characteristics. RESULTS Over a median period of 54months (inter-quartile range 47-65), a total of 138 deaths (15.2%) occurred, of which 24 were in the first 6months of follow-up. Cox regression analysis showed that high pre-procedural eosinophil count (top tertile) was associated with improved outcome within the first 6months (OR=0.23 [0.06-0.84]; p=0.03) but after this period there was an increased risk of mortality (OR=2.21, [1.26-3.88]; p=0.006). CONCLUSIONS Eosinophil count is a novel biomarker for risk stratification of CAD patients, which was associated initially with reduced mortality, but after 6months with increased mortality.

Impact of High-Dose Atorvastatin on Endothelial, Platelet, and Angiogenic Indices Effect of Ethnicity, Cardiovascular Disease, and Diabetes

Lipid lowering with statins improves morbidity and mortality, particularly in diabetics, and may have additional nonlipid effects. South Asians (SAs) are at higher risk of cardiovascular disease and diabetes compared with white Europeans (WEs). We hypothesized that abnormal endothelial (marked by von Willebrand factor), angiogenesis (VEGF, angiopoietins 1 and 2) and platelet function (soluble P selectin, soluble CD40L) improve with statin treatment in diabetics in different ethnic groups. Plasma was obtained before and 8 weeks after treatment with atorvastatin (80 mg/day) by SAs and WEs with or without diabetes. Research indices were measured by enzyme-linked-immunosorbent assay (ELISA). Treatment increased angiopoietin-2 (P < .04) in all groups regardless of diabetes or ethnicity. In those free of diabetes, angiopoietin-2 increased 3-fold, whereas in diabetes, it increased 2-fold. We suggest that an additional effect of statins is to increase levels of growth factor angiopoietin-2 in the direction of normality. This effect is weaker in participants with diabetes.

Indices of angiogenesis, platelet activation, and endothelial damage/dysfunction in relation to ethnicity and coronary artery disease: Differences in central versus peripheral levels

Background. We hypothesized that indices of angiogenesis (vascular endothelial growth factor (VEGF), angiopoietins (Ang‐1 and ‐2), platelet activation (soluble P‐selectin)) and endothelial damage/dysfunction (von Willebrand factor (vWf)) would be more deranged in South Asians than in white Europeans when measured within the coronary sinus or coronary artery per se (that is, intracardiac sampling of blood supplying and draining the heart), as compared to measurements from the peripheral venous system. Methods. To test this hypothesis, we performed a cross‐sectional study of 87 subjects undergoing cardiac catheterization, where 43 were South Asian and 44 were white European. Results. South Asian participants were younger (P = 0.01) but had a lower rate of self‐reported smoking (P = 0.01). The extent of coronary atherosclerosis, assessed using presence of lesions>50%, number of vessels diseased and Gensini score, was comparable between the two ethnic groups (all P = NS). When samples were analysed from the coronary circulation or the femoral vein in relation to South Asian and white European ethnicity, there were no significant differences in the levels of VEGF, angiopoietins 1 and 2, soluble P‐selectin and vWf levels between the two ethnic groups. Conclusion. Indices of angiogenesis, platelet activation, and endothelial damage/dysfunction are comparable in South Asians and their white European counterparts. Our results suggest that their pathophysiological roles may be comparable in South Asians and white Europeans in the context of coronary artery disease.

Systemic and intracardiac vascular endothelial growth factor and angiopoietin-1 and -2 levels in coronary artery disease: effects of angioplasty.

Background. Vascular growth factors are involved in the pathophysiology of human atherosclerotic vascular disease and plaque destabilization. We hypothesized that in stable patients with coronary artery disease (CAD), plasma levels of vascular endothelial growth factor (VEGF) and angiopoietins 1 and 2 (as indices of angiogenesis) would be no higher in coronary sinus blood when compared to the aortic root, coronary ostium, and peripheral femoral vein. Secondly, we hypothesized that percutaneous coronary intervention (PCI; angioplasty±stenting) would increase intracardiac levels of these indices, perhaps by destabilizing coronary plaques. Methods. Patients undergoing elective diagnostic coronary angiography (n = 70; mean age 58.8±11.2 years) of which 37 proceeded to PCI were recruited. Blood samples were obtained from the aortic root, coronary ostium, coronary sinus, and femoral vein. Plasma VEGF, angiopoietin‐1 and angiopoietin‐2 levels were measured by immunoassays. Results. There were no significant differences in VEGF, angiopoietin‐1 and angiopoietin‐2 levels when aortic root, coronary ostium, coronary sinus, and femoral vein samples were compared (P = not significant (NS)). In patients undergoing PCI, peripheral angiopoietin‐2 levels were increased significantly post PCI (P = 0.01). There was also a difference in intracardiac gradient (that is, aortic root‐coronary sinus difference) in angiopoietin‐1 (P = 0.02) following PCI. No significant changes in VEGF with PCI were noted. Conclusion. There were no differences in indices of angiogenesis when aortic root, coronary ostium, coronary sinus, and femoral vein levels of VEGF and angiopoietins are compared, suggesting that peripheral blood measurements of these indices are comparable to intracardiac levels. Although no immediate effects were observed in soluble VEGF levels, PCI affected intracardiac angiopoietin‐1 with a systemic release of angiopoietin‐2. Further investigations are necessary to determine the relative systemic and intracardiac effects of the angiopoietins in vascular remodelling post PCI.