Stefania Colonna

Endothelin-1 and its mRNA in the wall layers of human arteries ex vivo.

BACKGROUND The participation of endothelin-1 (ET-1) in the control of vascular tone in humans has been questioned, on the basis of the finding of subthreshold immunoreactive (ir) ET-1 plasma levels. However, because most ET-1 is secreted abluminally, it might attain a higher concentration in the tunica media than in plasma. Furthermore, evidence indicates that vascular smooth muscle cells (VSMCs) can synthesize ET-1 on stimulation in vitro. We therefore looked for irET-1 in the different layers of the wall of human arteries, including renal, gastric, and internal thoracic artery wall, obtained ex vivo from consenting patients with coronary artery disease and/or high blood pressure undergoing surgery, as well as from young organ donors. METHODS AND RESULTS We performed immunohistochemistry with specific anti-ET-1 and anti-vWF antibodies followed by detection with an avidin-biotin complex ultrasensitive kit. The presence of preproET-1 and human endothelin-converting enzyme-1 (hECE-1) mRNA was also investigated by reverse transcription-polymerase chain reaction in homogenates of vessel wall, including preparations deprived of both endothelium and adventitia, and in isolated VSMCs. We detected irET-1 in the endothelium of all arteries and in the tunica media of internal thoracic artery from most patients with coronary artery disease. PreproET-1 and hECE-1 mRNA was also detected in VSMCs isolated from these vessels. irET-1 and irvWF staining in endothelium and tunica media was measured by use of microscope-coupled computer-assisted technology. Significant correlations between the amount of irET-1 in the tunica media and mean blood pressure (P<0.05), total serum cholesterol (P<0.05), and number of atherosclerotic sites (P<0.001) were found. Thus, in organ donors, irET-1 was detectable almost exclusively in endothelial cells, whereas in patients with coronary artery disease and/or arterial hypertension, sizable amounts of irET-1 were detectable in the tunica media of different types of arteries. In addition, VSMCs isolated from these vessels coexpressed the preproET-1 and hECE-1 genes. CONCLUSIONS Collectively, these findings are consistent with the contention that endothelial damage occurs in most patients with atherosclerosis and/or hypertension and that ET-1 is synthesized in VSMCs of these patients.

Under treatment with lipid-lowering drugs of high-risk coronary heart disease patients of the GENICA study.

Objectives To assess the proportion of high-risk coronary artery disease (CAD) patients who received lipid lowering drug treatment (LLDT) and met the LDL-Cholesterol (LDL-C) goal of 100 mg/dl defined by the third report of the U.S. National Cholesterol Education Program (NCEP). Methods In 86% (n = 1095) of the 1268 consecutive Italian patients, who were enrolled in the GENICA study after undergoing quantitative coronary angiography for suspected coronary artery disease between 1999 and 2001, the levels of total serum cholesterol, HDL-cholesterol, triglycerides, and LDL-C were measured and accurate information on current LLDT were available. All patients were classified according to the NCEP. Results Seventy-four percent of the patients (n = 805) had established CAD and cardiovascular events and therefore were candidates for secondary prevention with LLDT; 69% of them had concomitant hyperlipidemia. Only 57% of the patients with CAD and hyperlipidemia were on LLDT. Of the 1052 patients who were at the highest risk class according to NCEP, only 34.2% and 16.7% were on LLDT and reached the LDL-C goal, respectively. Conclusions Only 1 patient of 6 in the highest-risk class according to the NCEP accomplished the LDL-C goal. Accordingly, in the field of secondary prevention of coronary artery disease, the implementation of guidelines that emerged from scientific evidence into clinical practice with LLDT still requires major efforts.

Funnel Technique for First-Line Endovascular Treatment of an Abdominal Aortic Aneurysm with an Ectatic Proximal Neck

Purpose: To describe a novel endovascular technique for proximal stent-graft fixation in an abdominal aortic aneurysm (AAA) with an ectatic aortic neck. Case Report: An 84-year-old man with multiple comorbidities and an asymptomatic 7-cm infrarenal AAA with a 38-mm aortic neck diameter was treated with a 3-component Talent-LPS stent-graft system. After the left internal iliac artery was embolized with coils, a 34times16times170-mm Talent bifurcated stent-graft was placed in the lower part of the AAA. A 44-mm-diameter, 90-mm-long free-flow thoracic tube endograft (6-mm oversizing) was delivered to the proximal neck through the bifurcated device and deployed with at least 30 mm of overlap, leaving more than 40 mm extending into the infrarenal aorta to ensure expansion to its nominal diameter as well as an adequate seal. An iliac extension was deployed into the left external iliac artery, and 2 sequential iliac extensions were inserted from the bifurcated stent-graft limb to the right common iliac artery in a bell-bottom configuration. Serial computed tomographic angiograms at up to 18 months have documented the intact 3-component stent-graft, with no endoleak or migration and no increase in aneurysm sac diameter. Conclusion: This case illustrates the feasibility of placing a straight thoracic endograft as a proximal extension of a bifurcated aortic endograft into a dilated proximal aortic neck. This endograft configuration appears secure and effective, with no type I endoleak or migration over a midterm follow-up.

Exon 11 deletion in the myocyte enhancer factor (MEF)2A and early onset coronary artery disease gene in a Sicilian family

Aims: We investigated the prevalence of the myocyte enhancer factor (MEF)2A exon 11 deletion, a putative coronary artery disease (CAD) susceptibility gene, in patients referred for coronary angiography. Methods and results: In total, 1079 consecutive patients referred for coronary angiography in the GENICA Study were genotyped and 301 low-risk subjects were used as controls. One patient with early onset three vessels CAD, carrying the MEF2A deletion was found in the GENICA Study cohort and none in the control group. Conclusion: In a cohort of patients undergoing coronary angiography for suspected CAD the MEF2A exon 11 deletion occurred in 0.09%.

Relation between the C677T transition in the methylentetrahydrofolate reductase gene, plasma homocyst(e)ine and folate levels, and coronary artery disease in the GENICA (Genetic and Environmental Factors in Coronary Atherosclerosis) study

treated cells, a number of differentially expressed transcripts were identified and cloned. Sequence homology search revealed and matched the identified clones to 1) a small subset of genes known to be involved in angiogenesis, e.g. platelet endothelial cell adhesion molecule 1 (PECAM-I), matrix metalloproteinase 2 (MMP2), endothelin converting enzyme 1 (ECE-I), and vascular endothelial growth factor receptor 2 (VEGFR-2); 2) a large subset of known genes with known function, but not involved in angiogenesis to date; and 3) about 5-10% of the clones were novel genes with unknown function, such as a putative G-protein coupled receptor. Thus there are clusters of related gene products, differentially regulated and involved with cholinergic, proliferative and apoptotic action. cDNA rmcroarray analysis (-48,000 elements) validated our findings Conclwon: Nicotme promotes angiogenesis through stimulation of angiogenic mechanisms partly through the cholinerglc pathway. Therapeutic modulation of nAChR may be useful in dlsorders of angiogenesis.