Asymmetric dimethylarginine and impaired cardiovascular healing.

Asymmetric dimethylarginine (ADMA) typically accumulates in the plasma of patients with chronic renal failure. Moreover, its plasma levels are raised in the presence of virtually all of the traditional cardiovascular risk factors. ADMA inhibits the three isoforms of nitric oxide (NO) synthase, thereby blunting the known cardioprotective effects of NO. Through its NO inhibitor actions, ADMA also exerts pro-apoptotic effects and suppresses progenitor cell mobilization, differentiation and function. Among patients with ischemic heart disease, low progenitor cell bioavailability and kidney dysfunction are emerging as strong predictors of death and recurrent cardiovascular events. We propose that patients with ischemic heart disease, kidney dysfunction, and high risk factor burden exhibit adverse cardiovascular outcomes, at least in part, through ADMA-mediated NO depression, enhanced apoptotic signalling, and reduced progenitor cell bioavailability, with consequent blunting of cardiovascular healing. Further research into the mechanisms that regulate the NO/ADMA balance may advance our understanding of cardiovascular diseases.

[Body mass index and cardiovascular events: the "obesity paradox"]. / Recenti acquisizioni sui rapporti tra indice di massa corporea e danno cardiovascolare: il "paradosso dell'obesità".

Excessive body mass among healthy subjects carries an increased risk of subsequent cardiovascular events. Excess weight implies the presence of white, viscero-abdominal fat, that promotes insulin-resistance, is infiltrated by macrophages, and is less differentiated compared to subcutaneous or brown fat. Conversely, among patients with cardiovascular disease, slim patients have a greater risk of recurrent atherothrombotic events than fatter patients ("obesity paradox"). Lean patients with cardiovascular disease, on average, have more comorbidities and haemorrhagic complications than their heavier counteparts, and probably they conceal predisposing factors that are still unknown and therefore difficult to treat.

[Recent advances in atherothrombotic diseases]. / Recenti progressi in tema di aterotrombosi.

New concepts in the field of atherothrombosis include the human potential to repair and regenerate areas of vascular damage through endogenous growth factors, and the identification of uncommon arterial thrombophilias that promote atherothrombosis. The endogenous factors erythropoietin and insulin-like growth factor-1 are emerging as robust opponents of the vascular and hemostatic alterations that occur in atherothrombosis. Both factors activate the intracellular Akt pathway and the biosynthesis of constitutive nitric oxide, with anti-apoptotic, insulin-sensitizing, vasodilator, anti-inflammatory, antioxidant and antiplatelet effects, all of which oppose arterial degeneration and occlusion. Additionally, erythropoietin and insulin-like growth factor-1 induce the mobilization of stem cells that can differentiate and repair areas of vascular damage thereby halting the progression towards established disease. In selected patients with an arterial thrombotic event, we believe it is justified to search for an uncommon acquired or inherited thrombophilic condition in the presence of at least one of the following: young age, recurrent events, lack of traditional metabolic or acquired vascular risk factors, and no significant artery stenoses at angiography. In these groups of patients, and in those with a marked family history of thrombosis, the prevalence of several functional polymorphisms of genes involved in the hemostatic system is significantly higher compared with controls. Acquired thrombophilias that should be searched for include the antiphospholipid syndrome, systemic lupus erythematosus, and myeloproliferative disorders.

EuroThrombosis: annual meeting of the European Society of Cardiology Working Group on Thrombosis.

EuroThrombosis is the annual meeting of the European Society of Cardiology Working Group on Thrombosis. It gathers clinicians and scientists interested in clinical/experimental thrombosis. The 2011 congress was held in Oporto, Portugal, and presented an appealing program with state-of-the-art sessions on new antiplatelet/anticoagulant agents, diabetes, cellular mechanisms of thrombosis and miRNAs.

A young man with intractable ascites and effort dyspnoea without echocardiographic signs of pericardial thickening: the importance of clinical investigation, CT scan and MRI in the diagnosis of constrictive pericarditis.

A 35-year-old male patient suffering from dyspnoea on effort for 8 months, with abdominal and jugular venous distension, was previously studied in another hospital and discharged with a diagnosis of restrictive cardiomyopathy. Physical examination revealed a blood pressure of 110/60 mm Hg and absence of pericardial knock and also of paradoxical pulse. Chest X-ray showed no cardio-pulmonary alterations. Transthoracic echocardiography showed mild LV dysfunction (LVEF 46%) and lack of pericardial effusion and thickening. Doppler interrogation of transmitral flow showed a restrictive pattern. Computed tomography showed diffusely thickened pericardium, with the absence of calcification and of pericardial effusion. Cardiac magnetic resonance confirmed pericardial thickening and showed lack of myocardial alterations. Mild LV dysfunction was noted with dyskinesia of interventricular septum. The patient underwent cardiac catheterization, demonstrating an equalisation of RV and LV diastolic pressures with "square root" sign. The patient underwent pericardiectomy with consequent resolution of his symptoms and improvement of LV function.

Erythropoietin in heart and vessels: focus on transcription and signalling pathways.

Erythropoietin (Epo) is synthesized mainly under hypoxic conditions by renal and extrarenal tissues, including liver, spleen, brain, lung, bone marrow, and reproductive organs. Hypoxia abrogates the degradation of hypoxia-inducible factors (HIF)-1 and -2, that can then bind to the hypoxia response element within the Epo gene, activating its transcription. Receptors for Epo are expressed on cells known to synthesize Epo, but also on cardiomyocytes, cardiac fibroblasts, and endothelial, retinal, gastric, prostate and vascular smooth muscle cells. Epo-receptor binding triggers at least three intracellular signalling cascades: (1) janus tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5); (2) phosphatidylinositol-3 kinase (PI3K)/Akt, and (3) RAS/mitogen-activated protein kinase (MAPK). Epo also enhances nitric oxide (NO) bioavailability through endothelial NO synthase transcription and activation, and exerts antiapoptotic actions through Bcl-2 and Bcl-XL. NO is a powerful vasodilator, insulin-sensitizer, inhibitor of atherothrombosis and apoptosis, and essential for progenitor mobilization. This article is a concise review of recent advances regarding the molecular and cardiovascular effects of Epo.

Lost and found: an unusual late complication of the Angio-Seal closure device.

We report an unusual case of breakage and embolisation of a femoral access closure device (Angio-Seal), which caused acute leg ischemia after percutaneous coronary intervention in a diabetic patient with documented peripheral vascular disease. Embolectomy from the superficial femoral artery revealed the polymer anchor split in two parts and embedded within a large (25x5 mm) thrombus.