Edoardo Perilli

Treatment of periodontal disease results in improvements in endothelial dysfunction and reduction of the carotid intima-media thickness

Several cohort studies reported a relation of cardiovascular events and periodontal disease. In particular, Porphyromonas gingivalis is associated with the development of atherosclerotic plaques. We verified in a longitudinal study whether inflammation biomarkers, endothelial adhesion molecules, leukocyte activation markers, and intima‐media thickness could be beneficially modified by periodontal treatment alone. Thirty‐five otherwise healthy individuals affected by mild to moderate parodontopathy were enrolled in the study. Echo‐Doppler cardiography of the carotid artery, fluorescence‐activated cell sorting analyses on lymphocytes and monocytes, and plasma inflammatory indices were evaluated at baseline and at multiple time points after the periodontal treatment. Results showed that inflammation biomarkers were abnormally increased at baseline. Periodontal treatment resulted in a significant reduction of the total oral bacterial load that was associated with a significant amelioration of inflammation biomarkers and of adhesion and activation proteins. Notably, intima‐media thickness was significantly diminished after treatment. Inflammatory alterations associated with the genesis of atherosclerotic plaques are detected in otherwise healthy individuals affected by parodontopathy and are positively influenced by periodontal treatment. Reduction of oral bacterial load results in a modification of an anatomical parameter directly responsible for atherosclerosis. These results shed light on the pathogenesis of atherosclerosis and could have practical implications for public health.—Piconi, S., Trabattoni, D., Luraghi, C., Perilli, E., Borelli, M., Pacei, M., Rizzardini, G., Lattuada, A., Bray, D. H., Catalano, M., Sparaco, A., Clerici, M. Treatment of periodontal disease results in improvements in endothelial dysfunction and reduction of the carotid intima‐media thickness. FASEB J. 23, 1196–1204 (2009)

Basal nitric oxide production is not reduced in patients with noninsulin-dependent diabetes mellitus

Vascular disease is the leading cause of morbidity, disability and death in patients with noninsulin-dependent diabetes mellitus. Abnormalities in endothelium-derived nitric oxide (NO) have been demonstrated to be involved in the pathogenesis of vascular disease. By measuring hemodynamic responses to a NO synthase agonist or antagonist, previous studies have shown the presence of NO deficiency in patients with noninsulin-dependent diabetes mellitus, a method of assessing bioactive NO formation. However, direct biochemical evidence that this is the case, has not been produced. In vivo NO is metabolized into nitrate, an end breakdown product of NO, which can be used as an index of endogenous NO formation. To investigate further whether decreased basal synthesis of NO may be a major cause of endothelium-mediated vascular dysfunction in patients with noninsulin-dependent diabetes mellitus, the plasma nitrite/nitrate levels of 15 patients were examined and compared with 13 normal controls. The results showed that in basal conditions plasma nitrite/nitrate levels were not reduced in diabetic patients compared with normal controls (37.3 ± 14.7 versus 29.4 ± 8.6 μmol/l). It was concluded that in noninsulin-dependent diabetes mellitus patients, endothelium-derived basal NO formation is not impaired. This study, taken with previous observations, suggests that factors other than diminished basal NO production, such as reduced bioavailability of NO probably due to the augmented production of superoxide anion with subsequently increased inactivation of NO, contribute to the high incidence of vascular disease in patients with noninsulin-dependent diabetes mellitus.

Lp(a) in hypertensive patients

Lipoprotein(a) (Lp(a)) is considered an important risk factor for coronary disease, cerebrovascular pathology and re-stenosis of coronary bypass. Few studies have been conducted on this lipoprotein in essential arterial hypternsive patients. The purpose of our study was to measure the serum concentrations of Lp(a) and the main parameters of the lipid profile in a group of essential hypertensive patients not receiving pharmacological treatment and with no clinical signs of associated pathologies or organ damage. A total of 123 Caucasian essential arterial hypertensive patients (47 men and 76 women) were studied and compared with 89 controls (36 men and 53 women) matched in terms of age, sex, body mass index (BMI) and smoking habits. It was found that the hypertensive patients had higher plasma concentrations of Lp(a), total cholesterol (TC), triglycerides (TG) and very low density lipoprotein (VLDL-C) than controls (P < 0.01), with no differences in the plasma concentrations of lp(a) between the two sexes. only 10 hypertension patients and seven controls had plasma concentrations of lp(a) of over 30 mg/dl. lp(a) does not correlate with the main parameters of the lipid profile. we can confirm that hypertension and dyslipidaemia, which are two of the main risk factors for vascular diseases on an atherosclerotic basis, are often associated. however, higher plasma concentrations of lp(a), albeit within the normal range, could be an independent risk factor for atherosclerosis, and could contribute towards increasing the incidence of cardiovascular disease in people with essential arterial hypertension.

Transglutaminase activity in rat liver after acute ethanol administration.

The acute effect of ethanol on hepatic transglutaminase (EC 2.3.2.13) activity and polyamine levels were investigated in the rat. A high dose of ethanol (5 g/kg body weight, given by gastric intubation) caused in homogenate and cytosolic fraction an inhibition of 50-70% from 3 to 24 h which thereafter was reversible. Such a decrease may be in part responsible for the observed enhancement in putrescine and spermidine contents observed at the same times. Pyrazole, an inhibitor of alcohol dehydrogenase, prevented the ethanol-induced reduction in transglutaminase activity. Disulfiram, an inhibitor of aldehyde dehydrogenase, allowed detection of an inhibitory effect on enzyme activity even at a low dose of ethanol (2 g/kg), which per se did not modify transglutaminase activity. The hepatic cytosolic fraction, incubated in the presence of various concentrations of acetaldehyde, showed a dose-dependent inhibition of transglutaminase activity. All of these results suggest that acetaldehyde, the first and toxic metabolite of ethanol, inhibits hepatic transglutaminase activity, probably by its binding to the active thiol site of the enzyme. The reduction in transglutaminase may lead to an alteration of cytoskeleton, since the enzyme is known to be involved in tubuline polymerization and microfilament assembly.

Elastic properties and structure of the radial artery in patients with type 2 diabetes

Alterations of elastic properties may contribute to the accelerated atherosclerosis in patients with T2D. Little is known, however, about radial artery distensibility in this patient group. A total of 19 patients with T2D and 19 controls were investigated.An echotracking system coupled to a plethysmograph was used to assess the morphologic and elastic properties of radial artery. Distensibility and compliance were evaluated using Langewouters’ equations. Distensibility and compliance did not differ significantly in patients with diabetes compared with controls. In contrast, radial IMT and WCSA were significantly higher in patients with T2D than in controls. Multiple regression analyses revealed a significant association between SBP and IMT (r 2 = 0.40, p<0.001) as well as WCSA (r = 0.54; r 2 = 0.30; p<0.001 ) in individuals with diabetes. In conclusion, distensibility and compliance of the radial artery are not reduced in patients with T2D. In contrast, radial IMT and WCSA are significantly higher in patients with T2D than in controls.These modifications are chiefly and positively related to SBP.

Impact of Mild hypertriglyceridemia on fibrinolysis, Lp(a), and platelet activation indexes in mildly hypercholesterolemic patients

The relationship between high triglyceride values and alterations of the fibrinolytic system in cardiovascular heart disease (CHD) patients is well known. The aim of the study was to evaluate the effect of moderate hypertriglyceridemia on fibrinolysis, lipoprotein(a) [(Lp(a)], and platelet activation indexes in asymptomatic patients. To this end, 46 nondiabetic, dyslipidemic patients (age 51±8 years), with no associated pathologies and 23 normolipidemic, homogeneus patients (in terms of age, sex, and smoke habits) were studied. The dyslipidemic patients were split up into two groups: 23 type IIb hyperlipoproteinemia patients (Group I), and 23 type IIa hyperlipoproteinemia patients (Group 2). The control group had total cholesterol values of <5.18 mmol/L and triglyceride concentrations of <2.25 mmol/L. The result showed a significant difference (p<0.05) in the baseline plasminogen tissue activator inhibitor (PAI-1 b) values for the Group 1 patients as compared with the Group 2 and the controls, in the baseline tissue plasminogen activator (t-PA b) values for the Group 1 patients as compared with the Group 2 patients and in the lipoprotein (a) (Lp(a)) (p<0.01) values for the Group 2 as compared with the controls. On the other hand, no statistically significant difference was observed in β-thromboglobulin (β-TG), platelet factor 4 (PF4). This study shows that mild hypertriglyceridemia in asymptomatic hypercholesterolemic patients is associated with a different regulation of the fibrinolytic mechanism. In patients with moderate hypercholesterolemia, higher blood concentrations of Lp(a) were found than in the controls.

Arterial stiffness and subendocardial viability ratio in patients with peripheral arterial disease

Arterial stiffening is a hallmark of the aging process and atherosclerosis, including peripheral arterial disease (PAD). We investigated the associations between carotid‐femoral pulse wave velocity (c‐fPWV), augmentation index corrected for heart rate (Aix@HR75), ankle brachial index (ABI), and subendocardial viability ratio (SEVR), an indicator of cardiac perfusion. The c‐fPWV, Aix@HR75, and SEVR was estimated using applanation tonometry. The ankle systolic pressure measurements for the calculation of the ABI were obtained using an 8‐mHz Doppler probe. The study group included 555 subjects, mean age 63 ± 11 years (248 PAD (ABI < 1.0), and 307 non‐PAD (ABI ≥ 1.0 ≤ 1.3). After the stepwise selection process in both PAD and non‐PAD patients SEVR was not related to c‐fPWV and ABI (P = .154; P = .156) and (P = .101; P = .402), respectively. In PAD patients, SEVR was negatively related to Aix@HR75 (P < .0001) and aortic PP (P = .0005). In conclusion, arterial stiffness is associated with non‐invasive indices of myocardial perfusion in PAD patients, suggesting a potential pathophysiological link for increased cardiovascular events.

Arterial Damage, Triglycerides, Apolipoprotein, and Lp-(a) Values in PVD Patients

The aim of the study was to provide a detailed apolipoproteic profile in stage II peripheral vascular disease (PVD) patients and to ascertain whether lower ankle/ arm pressure index (API) values were associated with a worse profile. Apolipoproteins of 83 stage II PVD patients (average age 64.7 ± 9.3 years) were selected and compared with those of a group of 44 normal control subjects, similar in terms of age, sex, and smoking and eating habits. Neither PVD patients nor controls had ever received lipid-lowering agents or defined dietary treatment. A diagnosis of PVD was confirmed by an API of <0.85. Arteriopathic patients were also split into two groups, depending on their API values, similar in terms of age, sex and smoking habits: API values of one group (n = 38) were ≥0.6, those of the other group (n = 45) were <0.6. The following biohumoral parameters were considered: fasting glycemia, total cholesterol, triglycerides (TGs); high-density lipoprotein cholesterol (HDL-C); low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), total cholesterol (TC)/HDL-C (TC/ HDL-C), Apoproteins (Apos) AI, AII, B, CII, CIII, and E; and lipoprotein a [Lp(a)]. HDL-C and Apo AI were lower (p < 0.01), while TC/ HDL-C ratios, Apo B, and Apo CII were higher (p < 0.01) in PVD patients compared with controls. The comparison between the two PVD groups with different API values showed higher blood TG and VLDL-C values for the patients with lower API values (p < 0.05), indicating a relationship between hypertriglyceridemia and greater arterial damage. Key Words: Peripheral arterial occlusive disease-Triglyceride-Lipoprotein a.