Diabetes, oxidative stress, molecular mechanism, and cardiovascular disease--an overview.

In recent years, diabetes and its associated complications have come to represent a major public health concern. It is a complex disease characterized by multiple metabolic derangements and is known to impair cardiac function by disrupting the balance between pro-oxidants and antioxidants at the cellular level. The subsequent generation of reactive oxygen species (ROS) and accompanying oxidative stress are hallmarks of the molecular mechanisms responsible for cardiovascular disease. Among several oxidative stress-mediated mechanisms that have been proposed, ROS-mediated oxidative stress has received the most attention. ROS have been shown to interact with proteins, lipids, and DNA, causing damage to the cellular macromolecules and subsequently, deterioration of cellular function. Induction of thioredoxin-1 (Trx1) gene expression has been demonstrated to protect the diabetic myocardium from dysfunction by reducing oxidative stress and enhancing the expression of heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF). The failure of antioxidants to consistently demonstrate clinical benefit necessitates further investigation of the role of oxidative stress in diabetes-mediated cardiovascular disease.

Cardiac amyloidosis, a monoclonal gammopathy and a potentially misleading mutation.

BACKGROUND: A 46-year-old Afro-Caribbean man presented with progressive dyspnea and recurrent syncope. Clinical examination revealed evidence of biventricular failure. INVESTIGATIONS: Electrocardiography, echocardiography, cardiac biopsy, measurement of serum levels of free light chain, scintigraphy with radiolabeled serum amyloid P component, transthyretin gene sequencing and immunohistochemistry. DIAGNOSIS: Cardiac acquired monoclonal immunoglobulin-light-chain amyloidosis with the incidental presence of the amyloidogenic transthyretin Val122Ile mutation. MANAGEMENT: The patient was referred for consideration of urgent cardiac transplantation and subsequent autologous stem cell transplantation. Unfortunately, he died suddenly within a few weeks of referral.

[Amyloid cardiomyopathy: a link between cardiology and hematology. A case report of positive response to standard therapy]. / La cardiomiopatia amiloidotica: un'interfaccia fra cardiologia ed ematologia. Descrizione di un caso clinico con risposta favorevole alla terapia tradizionale.

Cardiac involvement in primary systemic amyloidosis, due to amassing of fragments of light chains, is detected in the majority of cases. We report the case of a 56-year-old woman who came to our observation because of symptoms of congestive heart failure. Diagnosis of restrictive cardiomyopathy was made by echocardiographic examination, which showed right ventricular hypertrophy, disarray of interventricular septum and restrictive flow pattern at the mitral valve. Primary systemic amyloidosis was diagnosed by abdominal fat pad biopsy. Laboratory findings confirmed biopsy results, leading to the definite diagnosis of restrictive cardiomyopathy due to IgA kappa monoclonal gammopathy in primary systemic amyloidosis.

Immunological characterization and functional importance of human heart mast cells.

Mast cells are present in normal and even more abundant in diseased human heart tissue and their localization is of particular relevance to their function. Within heart tissue mast cells lie between myocytes and in close contact with blood vessels. They are also found in the coronary adventitia and in the shoulder regions of a coronary atheroma. The density of cardiac mast cells is markedly higher in some patients with myocarditis and dilated cardiomyopathy than in accident victims without cardiovascular diseases. More importantly, in some of these conditions there is in situ evidence of mast cell activation. We have described an original technique to isolate and purify HHMC for in vitro study. This procedure gives viable cells and after stimulation with immunological or non-immunological stimuli they release performed (histamine and tryptase) and newly generated mediators (PGD2 and LTC4). We have demonstrated that HHMC differ from those in other anatomical districts in that they are activated by specific immunological and non-immunological stimuli, and in their relation to the arachidonic acid metabolism, suggesting that the local microenvironment can influence their phenotypic and biochemical characteristics. Our own and other findings suggest that HHMC have complex and significant roles in different pathophysiological conditions involving the cardiovascular system. Direct activation of HHMC by therapeutic and diagnostic substances injected intravenously explains some of the anaphylactoid reactions caused by these agents. HHMC possess Fc epsilon RI and IgE bound to the surface and C5a receptors, which could explain how cardiac mast cells are involved in systemic and cardiac anaphylaxis. Cardiac mast cells and those in human coronary arteries also play a role in the early and late stages of atherogenesis and during ischemic myocardial injury. In conclusion, although studies of HHMC are in their infancy, their in vitro isolation may be useful in identifying additional mediators synthesized and released, stimuli relevant to human pathophysiology, and pharmacological agents selectively modulating the activation of these cells and their mediators. Drugs specifically acting on HHMC or on their mediators may eventually be useful in treating different cardiovascular diseases.

HLA investigations in cardiomyopathies.

Typization of HLA A, B and C antigens of peripheral lymphocytes was performed in 14 patients suffering from cardiomyopathy and in 10 family members from 10 families. Among the antigens of locus A, the most frequent were the subgroups of HLA A9 (A23 and A24) in 7/14, and those of HLA A10 (A25 and A26) in 3/14; frequent antigens of locus B were the types B5, B7, B12 and B35. In 2 of 10 families the cardiomyopathy was transmitted by autosomal dominant genes, while the other cardiomyopathy cases were sporadic. The HLA B8 antigen was not observed in any case of cardiomyopathy.