Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents) - Volume 9, Issue 2, 2011

High dietary intake of fruits and vegetables is consistently associated with a reduced risk of common human cancers. The specific mechanisms of action of most phytochemicals in cancer prevention are not yet clear but appear to be varied. One class of compounds currently under investigation is flavonoids, a large group of molecules with similar structure. Although their bioavailability is discussed, numerous in vitro and animal model data suggest that flavonoids modulate important cellular and molecular mechanisms related to carcinogenesis, a multistep process involving the transformation, survival, proliferation, invasion, angiogenesis, and metastasis of the tumor cells. Epidemiological studies confirmed that, among many flavonoids, apigenin, epigallocatechin gallate, delphinidin and genistein appear to be beneficial compounds in various stages of carcinogenesis. Therefore, according to in vitro and in vivo studies, this review attempts to increase our understanding about the preventive and therapeutic effects of these compounds to facilitate extrapolation of results from animal studies to human situations.

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been proposed as a biomarker of risk of cardiovascular disease (CVD). Objective: To determine the association between Lp-PLA2 activity and BMI, insulinresistance, components of the metabolic syndrome (MS), and lifestyle behaviors in healthy adolescent boys. Methods: Data were collected cross-sectionally from 164 adolescents from an amateur rugby club. BMI, blood pressure (BP), Tanner stages, glucose, insulin, lipids, and Lp-PLA2 activity were measured. Questionnaires for lifestyle behaviors were completed. Results: Approximately 26% of the adolescents were obese and 23% overweight. There was a univariate association between Lp-PLA2 and BMI (r=0.16;p=0.042), triglycerides (r=0.26;p=0.001), LDL-C (r=0.46;p>0.001), apo B (r=0.55;p>0.001), whereas waist circumference , BP, glucose, HOMA-IR, and HDL-C were not correlated. None of the lifestyle behaviors were significantly correlated with Lp-PLA2. In order to analyze Lp-PLA2 association with known CVD risk conditions, adolescents were categorized according to overweight/obesity and to the presence of metabolic syndrome. Conversely, as it was for LDL-C and apo B concentration, Lp-PLA2 activity was not higher in adolescents with obesity. Multiple regression analysis showed that apo B was significantly associated with Lp-PLA2 adjusted for age, BMI, triglycerides and LDL-C (R2=0.32). Conclusion: Lp-PLA2 activity was only associated with apo B adjusted for several confounding variables, suggesting that its clinical utility to identify individuals at risk for CVD does not surpass LDL-C and apo B in healthy adolescents. As plaque morphology may change with age, associations of Lp-PLA2 with CVD may likewise vary with age.

Interventional cardiology procedures and drug therapy have been widely applied for the treatment of occlusive vascular disease. However, there remains a critical lack of understanding of the disease process at a molecular level. Microarray technology has the unique advantage in the ability to analyze thousands of genes simultaneously. So far, several studies based on microarray analysis have already provided valuable expression data in diseases such as atherosclerosis and in-stent stenosis. This review summarizes: a) latest microarray research indentifying gene-expression profiles; b) the methodological analysis of the available microarray studies; c) generation of biological processes or pathways; d) detection of better diagnostic and therapeutic targets in atherosclerosis and in-stent stenosis. Further improvements in microarray interpretation as well as in study design, combined with definition and evaluation in the clinical arena, will enhance our understanding of the causes and mechanisms contributing to occlusive vascular diseases, and therefore will help to improve treatment of patients suffering from these diseases.

Hypertension is commonly associated with diabetes mellitus. The combination of hypertension with obesity and diabetes is a well recognized entity known as the metabolic syndrome, which shares a common pathophysiology of insulin resistance. The individual components of this syndrome act synergistically to substantially increase the risk of renal disease, stroke, coronary artery disease, and death. Hypertension increases both macrovascular and microvascular complications of diabetes such as neuropathy, nephropathy, coronary artery disease, stroke, and retinopathy. Hence there is a pressing need to achieve good control of hypertension to reduce such complications. Studies have been conducted to define target blood pressure in order to minimize such complications and also to decide on the type of drugs most likely to reduce complications/adverse events among diabetics. Along with the trusted and proven therapies to control blood pressure in diabetes, efforts should also be underway to define the hitherto unknown factors contributing to this problem and the ways to control them. There is also a need to prevent the development of diabetes among those predisposed to it and a defined approach needs to be established.

Coronary artery diseases continue to be the most common causes of mortality and morbidity in the industrialized world, especially in the setting of acute myocardial infarction. Platelets play a crucial role in thrombosis and haemostasis, which can be either beneficial or deleterious, depending on the circumstances. Platelet hyperreactivity is a multifactor process depending on genetic polymorphism, pathological state and lifestyle; it contributes to the activation of the thrombotic cascade. Under pathophysiological conditions platelets activation plays a critical role in arterial thrombosis including platelets aggregation, the basis of destabilization of coronary plaque. Despite the benefits observed in outcome when primary angioplasty is compared with thrombolysis for the treatment of acute myocardial infarction there is still some room for improvement; unfortunately the restoration of an “optimal” epicardial flow is not always related to an “optimal” myocardial reperfusion. In the recent, past several studies have shown significant benefits with the administration of glycoprotein IIb/IIIa inhibitors. Thus, the aim of the present review is to perform an update on factors associated with platelets hyperactivity and on adjunctive glycoprotein IIb - IIIa inhibitors in primary angioplasty.

Sickle Cell Disease (SCD) is one of the most prevalent hematological diseases in the world. Despite the immense progress in molecular knowledge about SCD in last years few therapeutical sources are currently available. Nowadays the treatment is performed mainly with drugs such as hydroxyurea or other fetal hemoglobin inducers and chelating agents. This review summarizes current knowledge about the treatment and the advancements in drug design in order to discover more effective and safe drugs. Patient monitoring methods in SCD are also discussed.

The presence of peripheral vascular disease along with coronary heart disease are the two components of generalized atherosclerosis. The risk of having one when the other is present is extremely high. There are four parts to consider in peripheral vascular disease management and these are prevention, plaque stabilization, percutaneous intervention and surgery. Each part has its place but no one would argue that prevention is best when risk is recognized and treated. Classic risk factors and the available diagnostic methods are discussed. Treatment of risk factors is presented with reduction of the low density lipoproteins as the established gold standard during the current era. Procedures of percutaneous vascular intervention with their procedural indications are presented and their advantages and disadvantages discussed. Surgical indications are presented with special indication due to major claudication, rest pain, or tissue loss. Prognosis is also considered and this prognosis is worse in more proximal peripheral vascular disease. Association with other diseases is an important part of prognosis, with the latter especially made worse by the presence of diabetes mellitus. Surprisingly, the long-term prognosis of peripheral vascular disease is worse than that of coronary heart disease. These patients have a significant increase of cardiovascular risk factors and of comorbidities. It has been shown that these patients are undertreated in spite of their high cardiovascular risk. It is mandatory that they receive the same intensive treatment of risk factors as that given to coronary heart disease patients.