Showing papers by "Francesco Cipollone published in 2010"

Atorvastatin Reduces Macrophage Accumulation in Atherosclerotic Plaques A Comparison of a Nonstatin-Based Regimen in Patients Undergoing Carotid Endarterectomy

Abstract: Background and Purpose— The object of our study was to compare the effect of high-dose vs low-dose atorvastatin vs nonstatin-based treatment (cholestyramine plus sitosterol) on cell composition of carotid plaque. Methods— We recruited 60 hypercholesterolemic patients (total cholesterol, 5.83–7.64 mmol/L) eligible for carotid endarterectomy. Three months before surgery, patients were randomized into 3 groups (n=20) receiving atorvastatin 10 mg/day (AT-10) or atorvastatin 80 mg/day (AT-80) or cholestyramine 8 g/day plus sitosterol 2.5 g/day. Analysis of cell composition was performed on endarterectomy specimens. Results— The 3 treatments resulted in a significant reduction of total cholesterol and low-density lipoprotein cholesterol (LDL-C), although the decrease in total cholesterol and LDL-C was of smaller magnitude in the cholestyramine plus sitosterol group. The 3 regimens did not influence the levels of inflammatory markers (including high-sensitivity C-reactive protein). Macrophage content was signifi...

Cyclooxygenase and Atherosclerosis: A Smoking Area

Abstract: Chronic smoking is associated with functional and structural vascular changes underlying inflammatory processes responsible for plaque formation and rupture. Cyclooxygenase (COX) is the key enzyme linking smoking action to inflammatory damages: it is responsible for the conversion of arachidonic acid to prostanoids, and lipid mediators involved in most of pathological processes. Two COX isoenzymes have been characterized, COX-1 and COX-2, that differ in terms of regulatory mechanisms of expression, tissue distribution, substrate specificity, and preferential coupling to upstream and downstream enzymes. The aim of this review is to highlight the pathogenetic role of chronic smoking in vasomotor dysfunction, inflammation, and modification of lipids underlying the initiation and the progression of atherosclerosis and to remark the hypothesis that plaque composition rather than plaque size is the real determinant of the plaque evolution toward rupture and the major responsible for acute ischemic syndromes. The concomitantly higher expression of EP4, COX-2, mPGES-1, MMP-2 and MMP-9 in unstable plaques is focused and the role of PGE(2) as pathophysiological link between smoking, COX-2 and MMP activity is stressed. Indeed, the intracellular pathways regulating COX-2 and the mechanisms suggested to clarify the role of COX-2 and downstream synthases in atherothrombosis are summarized.

Genetic and Molecular Determinants of Atherosclerotic Plaque Instability

Abstract: Arachidonic acid metabolism plays a key role in atherothrombotic events affecting the coronary or cerebrovascular territory, as reflected by experimental studies based on biochemical measurements of eicosanoid biosynthesis and the results of inhibitor trials in these settings. Two cyclooxygenase (COX)-isozymes exist, COX-1 and COX-2, that differ in terms of regulatory mechanisms of expression, tissue distribution, substrate specificity, and susceptibility to inhibition by drugs. Whereas the role of COX-1 expressed in platelets in acute coronary syndromes and ischemic stroke is definitely established through several large clinical studies with aspirin, the role of COX-2 activity in these settings is still unclear, because this enzyme was characterized only recently (1991) and its inhibitors (coxibs) only became available in 1998. In this review, we discuss the different expression profile of COX-2-related enzymes in the cells actively involved in atherothrombosis, the role of these enzymes as cause of plaque “instability”, and the clinical consequences of their inhibition. Recent studies suggest that variable expression of transmembrane and downstream receptors, as well as genetic mutations represent important determinants of the functional consequences of COX-2 expression and inhibition in different clinical settings.

Functional rs20417 SNP (–765G>C) of Cyclooxygenase-2 Gene Does Not Predict the Risk of Recurrence of Ischemic Events in Coronary Patients: Results of a 7-Year Prospective Study

Abstract: Objectives: The –765G>C variation (rs20417 SNP) in the promoter of cyclooxygenase-2 (COX-2) gene has been demonstrated to lower COX-2 enzyme activity in the vasculature, thus affect

Ambulatory monitoring of systolic hypertension in the elderly: Eprosartan/hydrochlorothiazide compared with losartan/hydrochlorothiazide (INSIST trial).

Abstract: Introduction Systolic hypertension is very common in the elderly and is strongly associated with the risk of cardiovascular and cerebrovascular events. The control of systolic hypertension is difficult and most patients require combination antihypertensive therapy. Few data are available regarding the efficacy of angiotensin II receptor antagonists on systolic hypertension of the elderly. The aim of this double-blind, double-dummy, randomized, parallel-group, multicenter study was to assess the efficacy of eprosartan 600 mg in combination with hydrochlorothiazide (HCTZ) 12.5 mg in comparison with losartan 50 mg in combination with HCTZ 12.5 mg, in reducing blood pressure in elderly patients with grade 2 systolic hypertension who did not optimally respond to eprosartan or losartan monotherapy.

Activity of Glutathione-Related Enzymes in Ischemia and Reperfusion Injury

Abstract: Myocardial ischemic injury is caused by severe impairment of the coronary blood supply usually produced by thrombosis or other acute alterations of coronary atherosclerotic plaques. Intense investigation has led to considerable insight into the pathobiology of myocardial ischemic injury.1,2