Vascular Disease Prevention (Discontinued) - Volume 4, Issue 1, 2007

Peripheral arterial disease (PAD) is a clinical setting affecting more than 5% of population older than 60. Despite the low rate of peripheral complications and amputation, PAD is complicated by high rate of coronary and cerebral events. For this reason PAD is considered a marker for systemic atherosclerosis and its early diagnosis may be helpful for identifying patients at risk for cardiovascular events. Experimental and epidemiological studies suggest a key role for oxidative stress in initiation and progression of the atherosclerotic process. In several clinical settings of atherosclerotic disease patients have evidence of enhanced oxidative stress but it is unclear if this finding helps to identify those who are at higher risk of cardiovascular complications. More limited are the data concerning the antioxidant status, that is a reflection of oxidative stress and should be lowered in case of diminished defence against oxidative stress. Despite the lack of this data many clinical trials have been done on the assumption that antioxidants could be of benefit in patients with atherosclerosis but the results have been disappointing. Because PAD is characterised by systemic atherosclerosis, it should be considered an interesting model to study the balance between oxidative stress and antioxidant status. This hypothesis is also based on the fact that PAD patients have several risk factors of atherosclerosis that are associated with enhanced oxidative stress. This paper will review the data concerning the balance between oxidative stress and antioxidant status in PAD trying to assess if in this clinical setting a rationale for the use of antioxidants does exist.

Recently, many investigators have reported that adipocytes secrete a variety of bioactive substances, termed adipokines (adipocytokines), including tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), leptin, resistin, adiponectin and so on. Adiponectin is most abundant in the plasma and produced exclusively by adipocytes. This adipokine has been reported to be an exciting player in the field of energy homeostasis regulation. Furthermore, adiponectin has been shown to have antiatherogenic properties in epidemiological, in vitro and in vivo studies. This review summarizes the currently available information regarding this important biomolecule and discusses its feasibility for the treatment of atherosclerotic diseases.

This study aims to investigate the alterations in the vascular reactivity of isolated aorta obtained in the early and late phase of adjuvant-induced arthritic rats and to determine the involvement of nitric oxide and prostaglandins in the pathogenesis of altered vascular reactivity ex vivo. Thoracic aortic rings obtained 7, 14, 21 and 29 days after adjuvant inoculation were used to assess contractile and relaxant responses in the absence and presence of aminoguanidine (0.1 mM) or indomethacin (0.01 mM). Phenylephrine contractility was significantly increased in 7-day arthritic aortae and restored with indomethacin in endothelium-intact rings. No significant difference in phenylephrine contractility of 14-day arthritic rings was observed. Contrarily, phenylephrine and KCl contractility were significantly inhibited in 21-day arthritic rings and reversed by aminoguanidine. Acetylcholine, but not sodium nitroprusside, relaxations were inhibited in all artritic groups, indicating a selective impairment in endothelial function, and restored with aminoguanidine. Endothelial dysfunction was confirmed histologically as the disintegration of endothelium in the intima without inflammatory cellular infiltration of tunica media or adventitia. Enhanced prostaglandin availability may have the major contribution in the development of increased vasoconstriction in the acute inflammatory phase of adjuvant arthritis, whereas overproduction of nitric oxide, probably endothelial in origin, may account for the hyporeactivity in the advanced phase of the pathology and for the endothelial dysfunction throughout.

Atherosclerosis and its consequences are the most rapidly growing vascular pathology in both developing and developed countries. However, most atherosclerotic plaques will remain harmless and only vulnerable plaques (a minority) have the potential of causing myocardial infarction. Disruption of the vulnerable plaque or plaque erosion and subsequent thrombosis is the most common pathophysiological mechanism leading to an acute coronary syndrome. Given the clinical importance of coronary plaque rupture and its consequences, a growing interest exists in the development and improvement of diagnostic modalities that will promptly and most importantly accurately detect and characterize the high-risk atheromatous plaque. These techniques may help risk stratification and allow the selection of the most appropriate therapeutic approaches. Current available techniques can be separated into invasive and non-invasive, the former providing more accurate information at this point of time, but non-invasive techniques are quite promising but require future follow up studies.

The objective of this study was to achieve enhanced delivery of doxorubicin to the brain through transferrincoupled liposomes. Doxorubicin-loaded liposomes were prepared and characterized for particle size, shape, percent encapsulation efficiency and in vitro drug release. Doxorubicin was labeled with 99mTc-DTPA and optimized to achieve high labeling efficiency. The in vitro stability was determined to check the efficiency of the system to establish the suitability of the radiolabeled system for in vivo studies. 99mTc-DTPA labeled doxorubicin bearing noncoupled and coupled liposomes was administered intravenously and biodistribution studies were performed. The distribution of doxorubicin via noncoupled and coupled liposomes was determined in various organs (i.e. lungs, liver, kidneys, spleen and brain) by measuring radioactivity using a gamma scintillation unit. An average 7-fold increased brain uptake of the drug was observed after liposomal delivery of doxorubicin, while the transferrin-coupled liposomes increased approximately 10 fold brain uptake of doxorubicin. We conclude that transferrin-coupled liposomes can enhance the brain uptake of drugs like doxorubicin.

An individual can be expected to live a healthy long life through the daily intake of beneficial dietary factors from a young age, independent of the presence or absence of genomic disorders. It is recommended to preferentially take food that contains substances favorably influencing cell viability and more importantly to minimize dietary factors that enhance cellular dysfunction and histological damage. Common sense would indicate that impairment of vascular function and histology accelerates age-dependent physical and mental deterioration; however, recent advances in medical research indicate that the term “vascular” should be replaced with “vascular endothelial”, which more accurately describes the situation Endothelial dysfunction is widely recognized as the most prominent triggering factor for the genesis of atherosclerosis and resultant serious cardiovascular diseases, such as myocardial infarction, angina pectoris, heart failure and stroke. One of the important factors maintaining the healthy endothelium and protecting against atheromatic changes is nitric oxide (NO) derived from endothelial cells, which is formed from L-arginine through catalysis by endothelial NO synthase (eNOS) in the presence of Ca2+, calmodulin and other cofactors. This gaseous, labile molecule elicits vasodilatation and inhibits platelet aggregation/adhesion, smooth muscle proliferation and LDL oxidation. NO formed by neurogenic (nNOS) and inducible NOS (iNOS) also contributes to regulate functions and histology in blood vessels, heart, kidney, corpus cavernosum and other tissues. Various ingested dietary factors influence endothelial function with the assistance of NO, its bioavailability being altered by the production, action and degradation of NO synthesized by NOS isoforms. Cholesterol, methionine/homocysteine, sodium, and cigarette smoking will be considered in this review as factors that impair functions of the endothelium, vascular smooth muscle or other tissues. Mechanisms underlying beneficial actions, in reference to NO, like dietary L-arginine, antioxidants, and polyphenols will also be discussed. Appropriate daily diets chosen for their health benefits are undoubtedly important not only in the prevention of disease but also as a strategy in patients on drug treatment. This review was separated into 5 Parts.

Full Text Available

Full Text Available

Full Text Available

Full Text Available