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Biomedical subjects

E Mele

Publications and source records attributed to E Mele.

26 records · Page 2Linked to original sources

Inhibition of cellular ras prevents smooth muscle cell proliferation after vascular injury in vivo.

Proliferation of smooth muscle cells of the arterial wall in response to local injury is an important aetiologic factor of vascular proliferative disorders such as atherosclerosis and restenosis after angioplasty. Ras proteins are key transducers of mitogenic signals from membrane to nucleus in many cell types. We investigated the role of ras proteins in the vascular response to arterial injury by inactivating cellular ras of rats in which the common carotid artery was subjected to balloon injury. DNA vectors expressing ras transdominant negative mutants, which interfere with ras function, reduced neointimal formation after injury. Our results indicate a key role for ras in smooth muscle cell proliferation and show that the local delivery of transdominant negative mutants of ras in vivo might prevent some of the acute vascular injury caused by balloon injury.

Animals↗

A polymorphism (G-->A transition) in the -78 position of the apolipoprotein A-I promoter increases transcription efficiency.

AG-->A transition at -78 base pairs from the transcription start site of the apolipoprotein A-I (apoA-I) gene has been associated with increased apoA-I serum levels in humans. We report here that this mutation (G-->A) increases significantly (5-7-fold) the expression of a reporter gene fused to the apoA-I promoter in human liver and intestine cells. In addition, the presence of A at -78 base pairs from the transcription start site of the gene significantly decreases the binding affinity of a nuclear factor present in liver and intestine cells. We suggest that the reduced affinity of this factor increases the transcription efficiency of the promoter and explains why individuals carrying the A allele have high serum apoA-I levels.

Adenine↗

Deletion polymorphism in the gene for angiotensin converting enzyme is associated with elevated fasting blood glucose levels.

The frequency and distribution of angiotensin converting enzyme insertion/deletion (ACE I/D) polymorphism, and its association with other known risk factors for coronary atherosclerosis, has been studied, in a normal south Italian population. Subjects homozygous for deletion showed elevated fasting blood glucose levels when compared with subjects homozygous for insertion. The difference was consistent with an increased number of type 2 diabetics among the former group of subjects.

Blood Glucose↗

SstI RFLP and hypertension as risk factors for extracoronary atherosclerosis in a male population of southern Italy.

The present study was designed to investigate on possible association between SstI polymorphism in the ApoAI-CIII-AIV gene cluster, classical coronary heart disease risk factors and extracoronary atherosclerosis. One hundred and twenty six male subjects were enrolled and underwent echo-Doppler examination of carotid and femoral arteries, coronary heart disease risk factors assessment and SstI genotyping. The frequency of the rare SsI allele was 12.1% and 6.7% in subjects with or without extracoronary lesions respectively and was not associated with differences in the distribution of coronary heart disease risk factors. Forty subjects had hypertension, 34 homozygous for the frequent allele and 6 with presence of the rare allele. Among these, 10 subjects (29%) and 5 subjects (83%), respectively, had extracoronary atherosclerosis. Furthermore, subjects homozygous for the rare allele exhibited lipid abnormalities and a family history positive for hypertension and/or hyperlipidemia. These findings suggest a possible role for the ApoAI-CIII-AIV gene complex in both lipid metabolism and blood pressure regulation and could be of help to identify, within hypertensives, those subjects prone to extracoronary atherosclerosis.

Alleles↗

Linkage disequilibrium of three polymorphic RFLP markers in the apolipoprotein AI-CIII gene cluster on chromosome 11.

We analysed the allelic and genotypic frequencies of three restriction fragment length polymorphisms in the region of chromosome 11 encoding apolipoprotein AI and CIII genes in a free-living population from South Italy (Calabria). These markers are located at -2500 and -78 bp from the transcription start site of apolipoprotein AI gene (XmnI and MspI, respectively), and in the 3' untranslated region of apolipoprotein CIII gene (SstI). XmnI and SstI label rare alleles (X2 and S2 indicate the presence of the site), whereas the absence of the MspI site (because of a G to A transition) marks the rare allele, M2. Pairwise linkage disequilibrium analysis was determined. Two significant non-random associations were found: a positive disequilibrium between ApoA1/XmnI and ApoA1/MspI markers (P < 0.0001), and a negative disequilibrium between ApoA1/XmnI and ApoC3/SstI markers (P < 0.05). Statistical analysis showed a significant difference in the S2-M2 haplotype frequency between the group of subjects with serum cholesterol levels in the highest decile (P < 0.005) and the group with serum cholesterol levels below the highest decile. The allelic frequency for each locus showed no significant difference between the two groups for all other metabolic parameters, included total cholesterol serum levels. These haplotypes are a more precise measure of genetic variations in the apolipoprotein cluster and their use should allow the mapping of mutations responsible for high serum cholesterol levels.

Adult↗

The prognostic value of right atrial pacing after acute myocardial infarction.

We performed right atrial pacing in 90 consecutive patients 10 to 30 days (mean 16.8 days) after acute myocardial infarction. Right atrial pacing was normal in 28 patients, depression of the ST segment occurred in 27 patients, systolic blood pressure fell below control values in 20 patients and, in 15 patients, right atrial pacing was non-diagnostic. Follow-up was from 12 to 28 months (mean = 17.3). Global mortality was 11.1%, with none of the patients with normal tests dying, 11% of those with ST depression, 30% of those with induced hypotension (P less than 0.01) and 7.1% of those in whom pacing was non-diagnostic. Patients with high clinical risk at discharge in Peel Class III-IV, showed 41.2% mortality during the period of follow-up. None of those had shown normal responses to pacing, but those dying included 50% of the patients with ST depression and 66.7% of those in whom right atrial pacing induced hypotension. Development of new angina during the period of follow-up was more frequent among the patients with ST depression (33.3%) (P less than 0.001). Thus, our results showed that right atrial pacing was useful in predicting mortality after acute myocardial infarction. In patients at high risk, we observed that a fall of systolic blood pressure was the best predictor of mortality.

Blood Pressure↗

Effects of nitrates on R-wave variations after exercise in coronary heart disease: differences in patients with and without angina pectoris.

With the purpose of investigating the pathophysiology of changes in the R wave after exercise and its relationship with left ventricular function, we studied 44 patients with coronary heart disease. They were classified into the following three groups: group A, 11 patients with angina pectoris and no prior myocardial infarction; group B, 18 patients with angina pectoris and prior myocardial infarction; and group C, 15 patients with prior myocardial infarction but no angina. All patients performed two exercise tests; one was a control test, and the other was performed after the sublingual administration of 5 mg of isosorbide dinitrate. In group A, variations in the R-wave voltage in control test and in the test after isosorbide dinitrate were 1.5 +/- 0.8 mm and -1.2 +/- 0.9 mm (P less than 0.05), respectively. In group B, results were 1.2 +/- 0.7 mm on the control test and -0.7 +/- 0.6 mm after isosorbide dinitrate (P less than 0.002), and in group C were -1.6 +/- 1.2 mm on the control test and -0.7 +/- 0.7 mm after isosorbide dinitrate (not significant). Thus, the two groups of patients with angina showed an increase of the R-wave after exercise in the control test but a decrease after the administration of nitrates, whereas the patients without angina showed a reduced R-wave after exercise both before and after the administration of nitrates (like normal subjects). This study suggests that ischemic ventricular dysfunction with exercise results in an increase in the R-wave, while exercise after nitrates results in a decrease in the R-wave consistent with less or no ventricular dysfunction due to nitrate therapy.

Administration, Topical↗