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Adaptive immune responses are involved in all stages of atherosclerotic plaque development, including plaque complication (i.e., rupture, ulceration, etc), which may lead to the clinical occurrence of Acute Coronary Syndromes (ACS) [1]. Unstable coronary plaques, in addition to macrophages, contain a 10-fold increase in T-lymphocytes, as compared to stable plaques [2]. T-cells produce and release cytokines, and, in turn, regulate macrophage activity [3]; thus, T-cell activation, through cytokine production, might play a pivotal role in the pathophysiology of plaque complication [4]. Several studies have focused on cytokine plasma levels in patients with ACS, demonstrating that many of these substances are elevated in the systemic blood of patients with ACS (for a review, see Ref. [5]), some of which may even correlate with an adverse prognosis [6]. However, most of these studies have measured cytokine levels in the peripheral blood, raising the issue that the local cytokine milieu is still largely unexplored. This is not a trivial issue, since the assessment of the local inflammatory milieu could contribute to a better understanding of different inflammatory and immune-mediated pathways determining different outcomes in patients affected by ACS [7]. Twenty-eight patients with a clinical diagnosis of ACS and 16 patients with Stable Angina (SA) undergoing coronary angiography were studied. After coronary angiography, a 6 F multipurpose catheter was positioned into the Coronary Sinus (CS); thereafter, blood samples (4.5 mL) were simultaneously obtained from the CS and the ascending aorta (Ao) and placed in pre-chilled Vacutainer tubes containing sodium citrate. Transcoronary cytokine levels (expressed as a Δ% of CS–Ao levels) were measured by LuminexTM technology [8]. We found that transcoronary serum levels of IL-1β, IL-2, IL-6, IL12p40/70, IL-15, and IFN-γ – all of which can be ascribed to a Th1related response – were all significantly increased with the exception of IL-2. (Fig. 1, panel A). On the contrary, transcoronary serum levels of IL-4, IL-5, IL-10, IL-13, (Th2-related response) did not change significantly in patients with ACS as compared to SA patients, with the exception of IL-10 transcoronary levels, which were significantly lower in the ACS group (Fig. 1, panel B). Finally, we have found a significant increase in the transcoronary blood levels of EGF, eotaxin, MCP-1, IP-10, RANTES, and TNF-α in the ACS patients, as compared to their SA counterparts (Fig. 2). Systemic inflammation has been associatedwith an altered pattern of cytokine profile in patients with ACS [5]. However, many large studies attempting to link specific cytokine/chemokine levels to ACS have been inconclusive [9], probably because the inflammatory responses accounting for the outcome of the lesion occur predominantly at the level of the complicated plaque, which may not be paralleled by similar changes in the peripheral blood. Therefore, consistent with this hypothesis, we have focused our attention on the local, i.e., intracoronary cytokine production profile in patients with ACS and compared it to patients with SA. In particular, we have observed that local cytokine release was characterized by an increase in the transcardiac levels of those substances which characterize a Th1-like type of immune response. In contrast, the local production of those cytokines which represent the “fingerprint” of the Th2-like response, did not change significantlywhen compared to that found in patients with SA. Interestingly, the transcoronary levels of IL-10, a cytokine able to down-regulate the inflammatory responses via multiple mechanisms, were even lower in ACS patients, as compared to those obtained in patients with SA. The observed increase in IP-10 and MCP-1 transcoronary blood levels also suggests that the recruitment of inflammatory cells is taking place locally, i.e., at the International Journal of Cardiology 176 (2014) 227–299

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.

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 adipocytederived molecules potentially involved in cardiovascular pathophysiology.

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.

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.

Aims 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. Methods and results 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). Conclusion 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.