Methanolic extract of Euchelus asper exhibits in-ovo anti-angiogenic and in vitro anti-proliferative activities

BACKGROUND: The marine environment is a rich source of bioactive natural products. Many of the marine bioactive compounds have been derived successfully from molluscs. Euchelus asper is a marine mollusc which is commonly found in the intertidal rocky regions of the Mumbai coast. The present study was focused on evaluating the anti-angiogenic and anti- proliferative activities of methanolic extract of Euchelus asper (EAME). METHODS: The anti-angiogenic activity of EAME (50-800 µg/mL) was assessed by chick chorio-allantoic membrane (CAM) model wherein multiple parameters in the CAM blood vessels were analysed through morphometric and histo-logical investigations. In vitro testing of EAME (5-20 µg/mL) included its cytotoxicity against three different cancer cell lines, its effect on cell proliferation by wound healing assay as well as their relevant molecular mechanisms. Statistical analysis was carried out by two-tailed student's t test for two unpaired groups. RESULTS: Analysis of CAM revealed that the extract is effective in reducing the branching points of the 1st order blood vessels or capillaries of CAM. Histological analysis of CAM showed significant decrease in capillary plexus and compartmentalization along with increase in mesodermal blood vessels, thus establishing its anti-angiogenicity. Further, EAME exhibited moderate but significant cytotoxicity against A549 non-small cell lung carcinoma cell line. We also demonstrated that the cytotoxicity of EAME in A549 was associated with its apoptotic activity by subG1 phase arrest. Lastly, EAME significantly reduced A549 proliferation by reducing the expression of Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9). CONCLUSION: Overall, our study suggested that EAME has potential to inhibit tumour angiogenic and proliferative activity and may be a potential source for development of new anti-cancer pharmaceuticals.

Association of carotid intima-media thickness with left main coronary artery disease.

BACKGROUND: Previous studies have shown that carotid intima-media thickness correlates well with the presence and extent of coronary artery disease. This study was conducted to determine whether it could reliably predict the presence of left main coronary artery disease. METHODS: Common carotid intima-media thickness was measured in 50 patients with angiographically proven significant (> or =50%stenosis) left main coronary artery disease and in another 50 age- and sex-matched patients with coronary artery disease without the involvement of the left main coronary artery. Measurements of the carotid intima-media thickness were made on the far wall 1 cm from the distal end of the common carotid artery bilaterally, and the average and the greater of the two values thus obtained for each patient were used for analysis. Plaques were not included in the measurement of carotid intima-media thickness. RESULTS: The average and greater of the two values were significantly higher in patients with left main coronary artery disease as compared to those without it (average intima-media thickness: 0.926 +/- 0.12 vs. 0.78 9 +/- 0.16 mm; p< 0.001; greater intima-media thickness: 0.994 +/- 0.13 vs. 0.844 +/- 0.20 mm; p< 0.001). The cut-off values of 0.81 mm for the average carotid intima-media thickness and 0.87 mm for the greater carotid intima-media thickness were found to have optimum sensitivity (92% and 90%, respectively) and specificity (60% and 64%, respectively) for the detection of left main coronary artery disease. A higher cut-off value of 1.0 mm increased specificity to 92% and 84%, respectively, for the average and greater thicknesses, but sensitivity decreased markedly. CONCLUSIONS: There is a significant association between increased carotid intima-media thickness and the presence of left main coronary artery disease. The measurement of carotid intima-media thickness can be used with reasonably good sensitivity and specificity for the detection of left main coronary artery disease in patients who are undergoing evaluation for suspectedcoronary artery disease.

Prevalence of cardiovascular risk factors in Indian patients undergoing coronary artery bypass surgery.

BACKGROUND: Conventional cardiovascular risk factors (CVRFs) are known to influence short-term and long-term outcome following coronary artery bypass graft surgery (CABG). There has been recent increase in prevalence of CVRFs in general population in India. However no information is available regarding the prevalence of same in patients undergoing CABG. METHODS AND RESULTS: In this cross-sectional study, one thousand consecutive patients undergoing elective CABG were included and data on major CVRFs was obtained in them. Mean age of the patients was 59.73 +/- 9.5 years and 884/1000 (88.4%) patients were males. 505/994 (50.8%) patients had BMI > or = 25.0 kg/m2 and 747/994 (75.2%) had BMI > or = 23.0 kg/m2. Diabetes mellitus was present in 475/1000 (47.5%) patients (46.5% men and 55.2% women), hypertension in 709/1000 (70.9% overall; 70.8% men and 71.6% women) and dyslipidemia in 781/913 patients (85.6% overall; 84.5% men and 93.9% women). 213/913 (23.3%) patients had LDL > or = 100mg/dl, 662/913 (72.5%) patients had low HDL and 338/913 (37.0%) patients had elevated triglycerides. 199/1000 (19.9%) patients (18.7% men and 29.3% women) had family history of premature CAD and 545/1000 (54.5%) patients (53.4% men and 62.9% women) had at least one family member having CAD (irrespective of the age of onset). 94/1000 (9.4%) patients (10.4% men and 1.7% women) were current smokers and another 302/1000 (30.2% overall; 33.7% men and 3.4% women) had history of smoking in the preceding one year. 876/913 (95.9%) of all the patients had at least one of the five major CVRFs and only 37/ 913 (4.1%) patients (4.1% men and 4.3% women) were free of all these risk factors. Sixty-one of the 1000 patients (6.1%) were younger than 45.0 years of age. As compared to older patients, dyslipidemia, family history of premature CAD and smoking were commoner in patients less than 45 years of age. In contrast, diabetes and hypertension were more prevalent in the older individuals. CONCLUSIONS: The present study showed high prevalence of most of the conventional CVRFs, esp. diabetes, hypertension and dyslipidemia in Indian population undergoing CABG.

Carotid Intima-Media Thickness and Brachial Artery Flow-Mediated Dilatation in Patients with and without Metabolic Syndrome.

BACKGROUND, Metabolic syndrome has recently emerged as a marker of future cardiovascular risk. However its incremental value for this purpose, over conventional cardiovascular risk factors and diabetes mellitus in particular, is debated. The present study was conducted to determine the extent of subclinical atherosclerosis in patients with metabolic syndrome, and compare it with the same in individuals with cardiovascular risk factors not having metabolic syndrome. METHODS, A total of 156 individuals seeking outpatient cardiac consultation for various indications were included in the study and were divided into four groups - group 1: cardiovascular risk factors present but not metabolic syndrome (n = 60) : group 2 : metabolic syndrome without diabetes mellitus or coronary artery disease (n = 21) ;group 3: metabolic syndrome with diabetes mellitus without coronary artery disease ( n = 27) ;and group 4:patients with documented coronary artery disease (n = 48). Metabolic syndrome was diagnosed on the basis of Adult Treatment Panel III (ATPIII) criteria. All patients underwent assessment of carotid intima-media thickness and brachial artery flow-mediated vasodilatation. RESULTS, Both carotid intima-media thickness and brachial artery flow-mediated vasodilatation were similar in groups 1 and 2 (carotid intima-media thickness: 0.687 -/+ 0.13mm and 0.706 -/+0.23mm, p = 0.963; brachial artery flow-mediated vasodilatation: 11.80 -/+ 5.16% and 12.87 -/+ 7.04%, respectively, p =0.883) , but group 3 patients had significantly higher carotid intima-media thickness (0.774 +/- 0.15mm, p = 0.047) and significantly lower brachial artery flow-mediated vasodilatation (7.37 -/+ 6.12%, p -/+ 0.007) as compared to group 1 patients. There was no significant difference in the two parameters between groups 3 and 4 (carotid intima-media thickness in group 4:0.789 -/+ 0.16mm,p = 0.976 and brachial artery flow-mediated vasodilatation:5.86 -/+ 3.85%, p -/+ 0.709). CONCLUSIONS, In absence of diabetes mellitus, metabolic syndrome was not associated with greater extent of subclinical atherosclerosis compared to individual cardiovascular risk factors. Presence of diabetes mellitus, however, resulted in significant endothelial dysfunction and evidence of subclinical atherosclerosis, similar to that seen in patients with already established coronary artery disease.