[Show abstract][Hide abstract] ABSTRACT: Epidemiological evidence has shown that abdominal obesity is closely associated with the development of cardiovascular (CV) disease, suggesting that it might be considered as an independent CV risk factor. However, the pathophysiological mechanisms responsible for the association between these 2 clinical entities remain largely unknown. Adipocytes are considered able to produce and secrete chemical mediators known as "adipokines" that may exert several biological actions, including those on heart and vessels. Of interest, a different adipokine profile can be observed in the plasma of patients with obesity or metabolic syndrome compared with healthy controls. We consider the main adipokines, focusing on their effects on the vascular wall and analyzing their role in CV pathophysiology.
[Show abstract][Hide abstract] ABSTRACT: High-mobility group box 1 (HMGB-1) is a nuclear protein physiologically involved in the maintaining of DNA structure in the nucleus. When tissue damage occurs, necrotic cells as well as inflammatory cells, once activated, release this protein in circulating blood, where it seems to exert a direct proinflammatory action. Thus, HMGB-1 might be involved in the pathophysiology of several diseases, including cardiovascular disease. However, the experimental evidence has not yet clarified its cardiovascular role which is still debated. Specifically, it is still not completely resolved whether HMGB-1 plays a protective or detrimental role on cardiovascular function. In this review, we consider the role of HMGB-1 in pathological conditions and comment on the role of this protein in the cardiovascular disease.
[Show abstract][Hide abstract] ABSTRACT: Adipocytes are nowadays recognized as cells able to produce and secrete a large variety of active substances with direct effects on vascular cells, known as adipokines. Visfatin is a recently identified adipokine not yet completely characterized for its pathophysiological role in cardiovascular disease. Increased levels of visfatin are measurable in the plasma of patients with coronary artery disease and specifically in those with acute coronary syndromes (ACS). Several studies have indicated that Tissue Factor (TF) plays a pivotal role in the pathophysiology of ACS by triggering the formation of intracoronary thrombi following endothelial injury. This study investigates the effects of visfatin on TF in human coronary endothelial cells (HCAECs).
HCAECs were stimulated with visfatin in a concentration range usually measurable in plasma of patients with ACS and than processed to evaluate TF-mRNA levels as well as TF expression/activity. Finally, the role of NF-κB pathway was investigated.
We demonstrate that visfatin induces transcription of mRNA for TF by Real Time PCR. In addition, we show that this adipokine promotes surface expression of TF that is functionally active since we measured increased procoagulant activity. Visfatin effects on TF appear modulated by the activation of the transcription factor, NF-κB, since NF-κB inhibitors suppressed TF expression. Finally, we show that the nicotinamide phopsphoribosyltransferase enzymatic activity of visfatin seems to play a pivotal role in modulating the NF-κB driven regulation of TF.
Data of the present study, although in vitro, indicate that visfatin, at doses measurable in ACS patient plasma, induces a procoagulant phenotype in human coronary endothelial cells by promoting TF expression. These observations support the hypothesis that this adipokine might play a relevant role as an active partaker in athero-thrombotic disease.
Thrombosis Research 06/2012; 130(3):403-8. DOI:10.1016/j.thromres.2012.06.007 · 2.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity, the most common nutritional disorder in Western countries, is usually associated to cardiovascular diseases. However, the precise molecular pathways underlying this close association remain poorly understood. Nowadays, the adipose tissue is considered as an endocrine organ able to produce substances called adipo(cyto)kines that have different effects on lipid metabolism, closely involved in metabolic syndrome, and cardiovascular risk. The increased cardiovascular risk can be related also to peculiar dysfunction in the endocrine activity of adipose tissue observed in obesity responsible of vascular impairment (including endothelial dysfunction), prothrombotic tendency, and low-grade chronic inflammation. The present review aims at providing an up-dated overview on the adipocyte-derived molecules potentially involved in cardiovascular pathophysiology.
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo 03/2011; 76(1):13-21.
[Show abstract][Hide abstract] ABSTRACT: There is evidence that reactive oxygen species (ROS) are related to the development of cardiovascular disease (CVD). Results from many studies support the hypothesis that ROS released from various sources or dysfunctional mitochondrial respiratory chain play a role in the development of atherosclerosis and its complications. This phenomenon is due to ROS-mediated signalling pathways that are involved in the modulation of several vascular mechanisms. Various animal models have demonstrated that ROS have a causal role in atherothrombosis and other vascular diseases. Oxidative stress is being proposed as the unifying mechanism for many CVD risk factors. In particular, ROS may be responsible for plaque rupture and subsequent thrombosis which lead to myocardial infarction and stroke. Many drugs or agents have been tested to prevent or block oxidation underlying atherothrombotic processes, often with discordant outcomes. We observed that pre-treatment with some antioxidants, such as pyrrolidine dithiocarbamate (PDTC) or N-acetylcysteine, as well as some vitamins with recognized antioxidant properties, namely ascorbic acid (vitamin C), all-trans Retinoic Acid (atRA) and alpha-tocopherol (vitamin E) can suppress oxidative stress (OS)-induced Tissue Factor (TF) expression in human coronary artery endothelial cells. The present review, starting from our experimental observations, focuses on the influence of redox balance on atherothrombotic processes and on the effects of antioxidant treatment. A better understanding of the complex regulation of cellular redox balance could facilitate the development of newer antioxidants aimed at specific cellular targets. Research could also help assess the role of combination pharmacological intervention for the treatment and prevention of vascular disease.
Current Vascular Pharmacology 03/2010; 8(2):259-75. DOI:10.2174/157016110790887009 · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Drug-eluting stents (DES) have become routine therapy in clinical practice because restenosis is significantly reduced in patients treated with these devices. New generations of DES bearing newer antiproliferative drugs have been developed. Sirolimus was the first antiproliferative drug eluted by a DES (SES) while zotarolimus represents a sirolimus-derived, newer antiproliferative drug borne by a different kind of DES (ZES). This report describes two cases of different vascular response to concurrent side by side implantation of SES and ZES in the same vessel and highlights significant early restenosis of ZES as compared with SES.
Heart and Vessels 08/2009; 24(4):313-6. DOI:10.1007/s00380-008-1134-x · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity and cardiovascular disease are closely related. Leptin, an adipocyte-produced hormone, is associated with increased cardiovascular risk. Increased plasma levels of leptin are measurable in the plasma of obese individuals. However, the possible links between obesity and cardiovascular disease are not completely understood. C-reactive protein (CRP) is a predictor of future cardiovascular events and plays a role in atherothrombotic disease. Thus, we evaluated whether leptin might play a role in cardiovascular disease, investigating its effects on CRP production by human coronary artery endothelial cells in culture.
Leptin induced CRP mRNA transcription as demonstrated by semiquantitative and real-time polymerase chain reaction as well as the release of CRP in the culture medium in a concentration-dependent fashion. Leptin-induced production of CRP was mediated through the RhoA activation of protein kinase Cbeta since both protein kinase C and RhoA pathway inhibitors prevented these leptin effects. Lovastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, by modulating the RhoA activation, significantly reduced leptin-induced CRP production.
This study describes the close relationship between leptin and CRP, providing support to the view that this adipokine, besides being involved in the pathophysiology of obesity, might play a relevant role as an active partaker in obesity, inflammation and atherothrombosis.
Journal of Vascular Research 07/2009; 46(6):609-17. DOI:10.1159/000226229 · 2.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Assessment of left and right systolic atrial reservoir function in asymptomatic mitral stenosis (MS) by strain and strain rate imaging (SRI) and their prognostic power at 3 year follow-up was the purpose of this study. There is clear indication to treat (by surgery or percutaneous valvotomy) symptomatic patients with MS, whereas for the asymptomatic ones, the question is much debated. So, we need new echocardiographic parameters helpful for the management of asymtomatic patients. Atrial reservoir function by SRI could help in evaluation of these patients.
Fifty-three asymptomatic patients with MS and 53 healthy controls were evaluated by the standard echo-Doppler study [mitral valve (MV) area, mean gradient, systolic pulmonary pressure, left atrial (LA) width, LA volumes, LA compliance index] and by Doppler myocardial imaging (velocity, strain, and SR of both atria). The endpoint at 3 year follow-up was symptoms, hospitalization for cardiac cause, atrial fibrillation, thrombo-embolic events, valvular surgery, or percutaneous commissurotomy. LA width, volumes, and systolic pulmonary pressure were significantly increased in MS patients (P < 0.001). Atrial myocardial velocities and deformation indices were significantly compromised in MS patients (P < 0.0001). Significant correlation was found between atrial myocardial velocity and MV area (by pressure half-time method: P = 0.019, R = 0.41; by planimetric method: P = 0.016, R = 0.43). Peak systolic LA myocardial strain and SR were significantly correlated with atrial volumes (strain: P = 0.03, R = -0.28; SR: P = 0.0008, R = -0.42), with atrial compliance index (strain: P = 0.04, R = 0.26; SR: P = 0.04, R = 0.16), with atrial ejection fraction (strain: P < 0.0001, R = 0.56; SR: P = 0.03, R = 0.43). At 3 year follow-up, 22 (41%) patients had events. Comparing the MS patients who had events during the 3 year follow-up with those who did not, the former had bigger LA volumes, although these parameters did not reached a significant value, whereas atrial myocardial systolic SR was significantly impaired in patients with events. In multivariate analysis, the best predictor of adverse events was LA peak systolic SR average (P = 0.04; coefficient: 0.113; SE: 0.055; cut-off value of 1.69 s(-1) for LA peak systolic SR average) with a sensitivity of 88%, specificity of 80.6%, area under the receiver operating characteristic curve of 0.852 (SE: 0.048; 95% CI: 0.74-0.93, P = 0.0001).
Atrial myocardial deformation properties, assessed by SRI, are abnormal in asymptomatic patients with rheumatic MS. The degree of this impairment is predictor of events in a 3 year follow-up. SRI could be helpful in decision-making of asymtomatic patients with MS.
[Show abstract][Hide abstract] ABSTRACT: We report a case of an asymptomatic patient in whom a right atrial mass was fortuitously documented by echocardiography few months after a transcatheter radiofrequency catheter ablation for recurrent AF. No masses were seen in the cardiac chambers before the ablative procedure, raising important diagnostic and decision-making issues. The patient was referred to the surgeon and a diagnosis of right atrial myxoma was made.
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo 04/2009; 72(1):40-2.
[Show abstract][Hide abstract] ABSTRACT: The deleterious effects of cigarette smoke (CS) on cardiovascular morbidity and mortality are well established. Both active and passive smoking represent a major health hazard for both men and women. The great concerns related to the deleterious effects of CS on cardiovascular disease have been translated into various kinds of social interventions and targeted health policies since ever. The high health impact of cigarette smoking has driven a huge number of researches at the epidemiological, clinical and biological level. Nevertheless, even though many progresses have been made in understanding the mechanisms underlying the high disease burden associated to cigarette smoke, the exact components and the mechanisms by means of which it exerts its effects remain to be completely clarified as yet. The present paper reviews the main observations on the pathophysiology of smoke-related cardiovascular diseases, providing an up-to-date perspective about one of the main cardiovascular killers of our days.
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo 07/2008; 70(2):59-67.