Role of Isoprenoid Compounds on Angiogenic Regulation: Opportunities and Challenges.

Isoprenoids represent one of the largest classes of phytochemicals. The structural diversity of these compounds, as well as their remarkable biological activities, makes them suitable candidates for the development of novel therapeutic agents. Several isoprenoids have demonstrated promising potential in the modulation of angiogenesis processes, and therefore provide an appealing alternative and/or addition to the available pharmacotherapies. These compounds could be used per se or combined with standard therapies, which can potentially reduce the undesired secondary effects. Compounds like the sesquiterpenoid artemisinin, and its derivatives, or the diterpenoid triptolide have been successfully tested in a broad range of models (in vitro and in vivo). Moreover, sesquiterpenoids seem to be a promising resource of natural angiogenic modulators, as it can be attested by the significant number of recent publications in this subject. On the other hand, other isoprenoids, such as the triterpenoid ursolic acid, are still under-explored and further studies are needed to understand their role within angiogenic process. Further insights into isoprenoids mode of action in angiogenesis will hopefully pave the way towards their successful clinical use.

Reactive oxygen species and synthetic antioxidants as angiogenesis modulators: Clinical implications.

Angiogenesis is important for normal functioning of organism and its disturbances are observed in many diseases, called angiogenesis-related states. Reactive oxygen species (ROSs) play an important role in physiology, but high level of cellular ROSs is cytotoxic and mutagenic for the cells, i.e. it can lead to oxidative stress. In this review we discuss close relationship between ROSs and angiogenesis process. Substances counteracting free radicals or their action and oxidative stress are known as antioxidants. We postulate that antioxidants, by affecting angiogenesis, may modulate therapy results in the case of angiogenesis-related disease. Herein, we present some antioxidant preparations of synthetic (N-acetylcysteine, curcumin and its analogs, Probucol, oleane tripertenoid, EGCG synthetic analogs) and nature-identical (vitamin E and C) origin. Then, we analyze their angiogenic properties and their multidirectional molecular effect on angiogenesis. Most preparations reduce neovascularization and diminish the level of proangiogenic molecules, downregulating signaling pathways related to angiogenesis. Moreover, we discuss studies concerning anticancer properties of presented synthetic antioxidants and their application in several angiogenesis-related diseases. We conclude that therapy in angiogenesis-related diseases should be planned with consideration of the angiogenic status of the patient.

Biological therapies for the treatment of cutaneous wounds: phase III and launched therapies.

INTRODUCTION: Normal wound healing mechanisms can be overwhelmed in the setting of complex acute and chronic tissue injury. Biological therapies are designed to augment and/or restore the body's natural wound healing abilities. There are a variety of available and emerging technologies utilizing this approach that have demonstrated the ability to augment wound healing. AREAS COVERED: In this review, the clinical data on launched and emerging biological therapies for wound healing applications are summarized. The methodologies discussed include biological skin equivalents, growth factors/small molecules and stem cell-based therapies. EXPERT OPINION: While many products possess convincing clinical data demonstrating their efficacy in comparison to standard treatment options, more robust, controlled studies are needed to determine the relative value among established and emerging biological therapies. Future bioengineering and stem cell-based approaches are of particular interest due to the simultaneous correction of multiple deficiencies present in the nonhealing wound.

Resveratrol in cholesterol metabolism and atherosclerosis.

Resveratrol, a natural polyphenol produced by plants in response to environmental stress, has received great attention during the past few years due to its beneficial roles in longevity and glucose homeostasis. Resveratrol has been found to display antioxidant, anti-inflammatory, antifibrotic, and cardioprotective properties. Resveratrol reduces platelet aggregation, induces vasorelaxation, limits endothelial activation, and modulates lipid and lipoprotein metabolism. Although the mechanisms of action of resveratrol have not been completely defined, there is evidence that some of the effects of resveratrol may be mediated via activation of sirtuin 1 and AMP-activated protein kinase and through inhibition of the pleiotropic transcription factor nuclear factor κB. Pathways proposed to underlie resveratrol-mediated cardioprotection include reduction of oxidative stress and activation of endothelial nitric oxide synthase. Adenosinergic mechanisms may play a role in its atheroprotective activity. The ability of the nutraceutical resveratrol to positively influence the future treatment of cardiovascular disease is discussed.

Angiogenesis modulation: the "spice effect".

Spices have been used as flavoring agents since antiquity. Extensive research throughout the world has indicated that various phytochemicals present in spices play a critical role in the prevention and/or cure of several chronic diseases. Angiogenesis, the formation of new blood vessels, is regulated by a finely balanced equilibrium between pro- and anti-angiogenic factors. Any shift in this balance is linked to a wide range of human disorders. Experimental evidences suggest that anti- or pro-angiogenic strategies can contribute to the therapy of such disorders. The clinical benefits of the U.S. FDA-approved drugs that target angiogenesis are relatively modest due to their high toxicity and exorbitant cost. Therefore, there has been a renewed interest in identifying natural food sources for the development of novel and safer angiogenesis targeting agents. In this article, we discuss those dietary spices and their phytochemicals that have been experimentally found to target the angiogenic pathway.

[Results of treatments for critical limb ischemia: effectiveness and indications].

The treatment of critical limb ischemia (CLI), which is the end stage of arteriosclerosis obliterans and/or Buerger's disease, provides the ischemic tissue with oxygen, and arterial revascularization procedures such as bypass surgery and thromboendarterectomy, percutaneous transluminal angioplasty (PTA)/stent, sympathectomy, hyperbaric oxygenation, angiogenesis, medical treatment, etc. are performed. Successful bypass surgery on the crural and foot arteries is the most effective procedure, although it requires good skill and an autogenous vein of good quality. The results of thromboendarterectomy for the femoral artery are not sufficient and thromboendarterectomy for below-knee arteries is impossible. PTA/stent is the first choice of treatment for iliac arterial lesions. It is, however, not appropriate for below-knee arteries. Recently, many interventionists perform intraarterial treatment, although the intervention approved only because stenosis and/or occlusion is noted in the arteriogram. A correct diagnosis of the clinical severity of CLI in the leg is important for appropriate treatment. Sympathectomy of the lower limb is often effective in Buerger's disease. Hyperbaric oxygenation of the whole body is not currently performed. Angiogenesis is a new method, still in the experimental stage and its clinical effectiveness has not been confirmed. Anticoagulants, prostanoids, and antiplatelets are always necessary in the treatment of CLI.