Valter Lubrano - Academia.edu (original) (raw)

Papers by Valter Lubrano

Antioxidants, Jun 20, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Kardiovaskuläre Medizin, 1999

European Heart Journal, 2000

Thyroid hormones (TH) play an important role in heart vascular system, and both hyperthyroidism a... more Thyroid hormones (TH) play an important role in heart vascular system, and both hyperthyroidism and hypothyroidism are associated with altered cardiovascular system. Moreover, several evidences suggest that heart diseases trigger a reduction in cardiac tissue thyroid hormone levels.

American Journal of Hypertension, Jun 1, 2000

thickness in a population of normotensive healthy volunteers. Methods. A population of 88 healthy... more thickness in a population of normotensive healthy volunteers. Methods. A population of 88 healthy normotensive volunteers with wide age distribution between 18 and 65 years was studied (mean age 41.1 Ϯ 13.4 years, 47% men, 53% women). Carotid and femoral IMT were measured using a 10 MHz vascular echography probe (Vingmed System Five). Three measurements of carotid and femoral artery IMT were performed 1 to 2 centimeters proximal of the right carotid and right femoral artery bifurcations respectively, and the results were averaged. Results. Mean carotid IMT was 0.53 Ϯ 0.13 mm. Mean femoral IMT was 0.63 Ϯ 0.34 mm. Carotid and femoral IMT were significantly correlated (r ϭ 0.380; p Ͻ 0.001). However femoral IMT values showed a significantly wider scatter with increasing age: Levene's test for Ͼ45y, *pϽ0.05 in table of quartiles of age. Conclusion. These results show differential effects of aging on elastic and muscular large arteries, fitting within the concept of vascular heterogeneity. Although carotid and femoral intima-media thicknesses correlate closely, the wide scatter of values of femoral IMT in all but the youngest age groups precludes this parameter from being used in risk stratification.

PubMed, 2017

Angiogenesis is a physiological process required for embryonic vascular development and involved ... more Angiogenesis is a physiological process required for embryonic vascular development and involved in the pathophysiological progress of diseases such as atherosclerosis. In fact, hypoxia, ischemia and oxidative stress are common events in atherosclerotic plaque that stimulate angiogenesis, leading to the formation of a neovascularization in the intima of atherosclerotic lesions. The presence of these capillaries favours the progression of the plaque instability. Several studies indicate oxidized low-density lipoprotein (ox-LDL) and its endothelial receptor lectin-like oxidized low-density lipoprotein (LOX-1) as the major responsible for the occurrence and progression of atherosclerosis through apoptosis. At the same time, some authors showed that moderate concentrations of ox-LDL stimulate angiogenesis via LOX-1 activation of NADPH oxidase, MAPKs-NF-KB pathways and the generation of low levels of reactive oxygen species (ROS). Thyroid hormones have well documented effects on angiogenesis through genomic and non-genomic action and increased levels of ROS have been reported in hyperthyroidism. Moreover, by in vitro studies triiodothyronine (T3) and L-thyroxine (T4) significantly increased the intracellular ROS production based on the oxidation of 2',7'-dichloro dihydrofluorescein to a fluorescent 2',7'-dichlorofluoresein. Previous findings showed that ROS directly increase LOX-1 production in microvascular endothelial cells. New in vitro studies demonstrated the capability of T3 at supra-physiological doses to upregulate the LOX-1 expression in human microvascular endothelial cells. Thus, we can speculate the existence of a crosstalk between LOX-1-ROS and high levels of T3, suggesting that high levels of T3, as in hyperthyroidism, could cause a worsening of plaque vulnerability inducing angiogenesis.

PubMed, 2018

Several inflammatory factors have been determined as indicators of coronary artery disease (CAD) ... more Several inflammatory factors have been determined as indicators of coronary artery disease (CAD) and recently some studies showed neutrophyl to lymphocyte ratio (NLR) as a powerful predictor. The aim of this study was to evaluate NLR, comparing it with the consolidate inflammatory and oxidative stress marker in a group of control and CAD patients. Twenty healthy subjects and 47 patients, that were affected by 1-4 compromised coronary arteries, were enrolled in the study. All subjects were classified into 3 groups on the base of NLR tertile. The efficacy of NLR as indicator of the severity of CAD and its association with inflammatory markers were analyzed. According to the tertile of NLR, patients in the high NLR value had higher % of males, number of compromise coronary arteries, CRP levels, neutrophyl count, and low lymphocyte count. Moreover NLR and CRP levels showed to be independent predictors of 3-4 compromised coronary arteries. The ROC curve analysis showed that CRP and NLR markers had the largest area under the curve (AUC = 0,85, 95% CI: 0,74-0,96, p = 0,000; AUC = 0,81, 95% CI: 0,66-0,96, p = 0,001). In conclusion our data indicate that only NLR and CRP are independent predictors for 3-4 compromised coronary arteries.

PubMed, 2015

It is now widely accepted that the microcirculation plays a role in the complications of atherosc... more It is now widely accepted that the microcirculation plays a role in the complications of atherosclerosis, but the microcirculation response to atherosclerosis risk factors like diabetes, hypercholesterolemia and hypertension, is still unclear. Alterations in the endothelial production of IL6, NO and ET-1 are known to be correlate with these diseases. Simulating the presence of hyperglycemia, hypercholesterolemia and hypertension, this in vitro study investigated the effect of glucose, angiotensin II, and nLDL treatments on IL-6, ET-1 and NO in HMEC-1. The medium concentrations of IL6 and ET-1 were measured by ELISA assay, whereas NO by a colorimetric assay. The mRNA and protein expressions of IL-6, Pre-po-ET-1 and eNOS by extracted cells were also investigated by RT-PCR. NO concentration in the medium of HMEC-1 increased in a dose-dependent manner by glucose after 24 hours and by nLDL both at 6 and 24 h, with higher values at 6 hours. The eNOS mRNA expression at 6h induced by nLDL, showed a parallel trend to the medium NO. No increment dose dependent NO concentration was observed by angiotensin II.nLDL induced a dose-dependent increase of ET-1 medium levels, more accentuated in 6h respect to 24h. The expression of prepro-ET-1 showed a parallel dose-dependent increased after 6 hours. Both glucose and nLDL increased IL-6 levels in a dose-dependent manner at 6 and 24 h. In conclusion, glucose treatment on HMEC-1 cells exerted a mild stimulus on NO and IL-6 production. nLDL treatment showed a similar glucose stimulus on NOx, but it induced an intense pro-inflammatory activity and showed the ability to stimulate ET-1 synthesis.

PubMed, 2020

A few months ago a new coronavirus was identified in Cina officially named by the WHO as COVID-19... more A few months ago a new coronavirus was identified in Cina officially named by the WHO as COVID-19. The thousands of patients who died showed pneumonia and alveolar damage, but actually, according to several authors in addition to the acute respiratory distress syndrome the virus can give rise to multiorgan failure. In fact, many people died equally despite being intubated and treated for respiratory failure. In this review, we especially wanted to describe the virus effects on the cardiovascular system, probably the leading cause of death of thousands of deceased patients. Therefore, mortality is indirectly induced by the virus through vascular inflammation and cardiovascular damage and patients with severe COVID-19 infection showed significantly increased levels of cardiac troponin I and inflammatory cytokines. The main activation of the signal pathways for the production of inflammatory cytokines are the toll-like receptors that recognize the presence of viral nucleic acids and the ACE-2 receptors, that the virus uses to infect the cells. The binding to ACE-2 also allows to promote high levels of angiotensin II by promoting high levels of blood pressure. High levels of IL-6, IL-1B and IL-8 have been associated with plaque instability and increased thrombotic risk. Furthermore IL-6 is involved in the stimulation of matrix-degrading enzymes such as matrix metalloproteinases, and may contribute to the development of acute coronary syndrome. In addition, TNF-α, IL-1 and IL-6 present in patients with severe COVID-19 are associated with coagulation activation and thrombin generation resulting in disseminated intravascular coagulation or thrombotic microangiopathy. Considering these pathological effects of the virus, anti-inflammatory and anticoagulant treatments are to be considered to avoid cardiovascular events. In this regard, heparin, in addition to its anticoagulant characteristics, has been shown to have good control over inflammation and to be a good anti-viral drug.

Clinical and Experimental Medicine, Jun 1, 2006

Superoxide dismutase (SOD) is reported to be the major enzymatic defence against free radicals an... more Superoxide dismutase (SOD) is reported to be the major enzymatic defence against free radicals and common oxidants. EC-SOD is the only extracellular form of SOD present at a high concentration in vascular intima. The aims of the present study were to elucidate the role of EC-SOD in patients with coronary artery disease (CAD) and evaluate its association with free radicals, inflammation and with the severity of the disease. The study included 36 consecutive subjects with CAD being treated in the Institute of Clinical Physiology (33 males, 3 females) and 19 controls (16 males, 2 females). Each subject, after cardiac catheterisation and coronariography, was evaluated for serum EC-SOD activity, peroxy radicals, high-sensitive interleukin-6 (hs-IL-6), high-sensitive tumour necrosis factor (hs-TNFa) and high-sensitive C-reactive protein (hs-CRP) serum levels. The analysis of EC-SOD serum activity did not show any particular difference between patients and controls, while the serum levels of peroxy radicals, hs-IL-6 and hs-CRP showed a significant difference between the two groups (respectively: P<0.01, P<0.001, P<0.01). Moreover, enhancement of hs-IL-6 serum levels was also observed in severe disease (involvement of 3, 4 coronary arteries; P<0.05), while EC-SOD activity showed a slight increment in association with the number of arteries involved. hs-IL-6 concentrations were statistically significantly associated with peroxy radicals and CRP levels (respectively: P<0.05, r2=0.1; P<0.05, r2=0.14). The present study suggests a low effectiveness of EC-SOD activity in prevention against CAD and further confirms hs-IL-6 as a useful marker in diagnostic prevention and in clinical characterisation of CAD.

Clinical Chemistry and Laboratory Medicine, Jan 26, 2002

International Journal of Sports Medicine, 2003

In the present study we assessed the effect of physical training on Laser Doppler skin flux (LDF)... more In the present study we assessed the effect of physical training on Laser Doppler skin flux (LDF) and nitric oxide (NO) release, before and after 3 min of brachial artery occlusion. To this end we performed laser Doppler measurements and the venous plasma assay of nitrite/nitrate (NOx) on 10 sedentary healthy subjects and 10 endurance athletes. The sedentary control subjects had lower basal and post reperfusion levels of NOx as compared to athletes (mean +/- SE: 27.8 +/- 3.5 vs. 33.2 +/- 3.4, 48.6 +/- 7.9 vs. 60.1 +/- 10.1 micromol/L; p < 0.05). LDF at baseline was not significantly different in the two groups (157.5 +/- 7.9 and 176.64 +/- 26.7 PU for sedentary subjects and athletes, respectively) while post ischemic LDF was significantly lower in nonathletic subjects than in athletes (209.9 +/- 13 and 343.8 +/- 21.3 PU, p < 0.001). In both groups the hyperaemic stimulus significantly increased LDF and NOx levels (p < 0.01 and p < 0.05, respectively). The flow reserve, estimated as peak/basal LDF, was significantly lower in control subjects than in athletes (1.34 +/- 0.2 and 2.32 +/- 0.9, respectively, p < 0.01). In athletes, as opposed to sedentary subjects, a direct correlation was found between plasma NOx concentration and LDF both in basal conditions (r = 0.92; p < 0.001), and during hyperaemia (r = 0.84; p < 0.01). In conclusion, compared to sedentary subjects, athletes had an enhanced nitric oxide release. Hyperaemia increased LDF and nitric oxide levels both in sedentary subjects and in athletes.

Microvascular Research, May 1, 2016

Studies from human and animal models with metabolic disease and hypertension highlight atrophic r... more Studies from human and animal models with metabolic disease and hypertension highlight atrophic remodeling, reduced lumen size and thinner vascular walls of microvessels with profound density reduction. This impaired vascular response limits the perfusion of peripheral tissues inducing organ damage. These conditions are strongly associated with oxidative stress and in particular with the up-regulation of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1). Several factors such as cytokines, shear stress, and advanced glycation end-products, especially oxLDL, can up-regulate LOX-1. The activation of this receptor induces the production of adhesion molecules, cytokines and the release of reactive oxygen species via NADPH oxidase. LOX-1 is considered a potent mediator of endothelial dysfunction and it is significantly associated with reduced microvascular endothelium NO-dependent vasodilation in hypercholesterolemia and hypertension. Microvascular endothelial cells increased the expression of IL-6 in association with the increased concentration of LDL and its degree of oxidation. Moreover, increased IL-6 levels are associated with up-regulation of LOX-1 in a dose-dependent manner. Another consequence of microvascular inflammation is the generation of small amounts of ROS, similar to those induced by low concentration of oxLDL (&amp;lt;5μg/mL) which induces capillary tube formation of endothelial cells, through LOX-1 up-regulation. In light of its central role, LOX-1 represents an attractive therapeutic target for the treatment of human atherosclerotic diseases and microvascular disorders.

Life Sciences, Apr 1, 2018

Altered production of reactive oxygen species (ROS), causing lipid peroxidation and DNA damage, c... more Altered production of reactive oxygen species (ROS), causing lipid peroxidation and DNA damage, contributes to the progression of atherosclerosis and cancer. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a lectin-like receptor for oxidized low-density lipoproteins (ox-LDL) primarily expressed in endothelial cells and vasculature-rich organs. LOX-1 receptors is a marker for atherosclerosis, and once activated by ox-LDL or other ligands, stimulates the expression of adhesion molecules, pro-inflammatory signaling pathways and proangiogenic proteins, including NF-kB and VEGF, in vascular endothelial cells and macrophages. Several different types of cancer reported LOX-1 gene upregulation, and numerous interplays exist concerning LOX-1 in atherosclerosis, metabolic diseases and cancer. One of them involves NF-kB, an oncogenic protein that regulates the transcription of several inflammatory genes response. In a model of cellular transformation, the MCF10A ER-Src, inhibition of LOX-1 gene reduces NF-kB activation and the inflammatory and hypoxia pathways, suggesting a mechanistic connection between cellular transformation and atherosclerosis. The remodeling proteins MMP-2 and MMP-9 have been found increased in angiogenesis in atherosclerotic plaque and also in human prostate cancer cells.