E007 Differential effects of microparticles from human apoptotic T lymphocytes and from human apoptotic monocytes in endothelial cells

During cell activation or apoptosis, cells release vesicles, also called microparticles (MPs) from the plasma membrane. Since composition of MPs is dependent on cell origin and the type of stimulation, we compared the effects of MPs generated from both apoptotic T lymphocytes and apoptotic monocytes on endothelial function with respect to both nitric oxide (NO) pathway and reactive oxygen species (ROS). MPs were produced by treatment of either human T lymphocytes with the apoptotic agent actinomycin D or human monocytic cell line THP-1 with the apoptotic agent, the etoposide VP-16. Human Eahy 926 endothelial cells were incubated with 10μg/ml MPs for 24h. Apoptotic MPs from human T lymphocytes decreased NO production that was associated with overexpression and phosphorylation of endothelial NOsynthase (eNOS). Also, T lymphocytes MPs enhanced expression of caveolin-1 and decreased its phosphorylation. T lymphocytes MPs enhanced ROS by a mechanism sensitive to xanthine oxidase and P-IkappaBalpha inhibitors. PI3-kinase inhibition reduced the effects of T lymphocytes MPs on eNOS, but not on caveolin-1, whereas it enhanced the effects of MPs on ROS production. Inhibition of MEK reversed eNOS phosphorylation but it had no effect on ROS production induced by T lymphocytes MPs. By contrast, apoptotic MPs from human monocytes increased both NO production and in much less extent ROS. These effects were associated with a decrease of caveolin-1 expression and increased its phosphorylation, without affecting eNOS expression and phosphorylation. The inhibitor of the PI-3kinase, LY294002, reversed the effects of monocyte MPs on caveolin-1 expression but not on its phosphorylation. The MEK1/2 inhibitor, U0126, reversed the decrease of caveolin-1 expression induced by MPs from monocytes. Interestingly, U0126 potentiated ROS production induced by monocyte MPs. Whereas in vivo injection of T lymphocytes MPs in mice impaired endothelial function, apoptotic MPs from human monocytes did not affect endothelium-dependent relaxation. In addition, monocyte MPs were able to promote in vitro angiogenesis. In summary, these results highlight differential effects of apoptotic MPs from different origins by activating diverse multiple pathways related to NO and ROS productions

Curcumin as prospective anti-aging natural compound: Focus on brain

The nutrients and their potential benefits are a new field of study in modern medicine for their positive impact on health. Curcumin, the yellow polyphenolic compound extracted from Curcuma longa species, is widely used in traditional Ayurvedic medicine to prevent and contrast many diseases, considering its antioxidant, immunomodulatory, anti-inflammatory, anti-microbial, cardio-protective, nephron-protective, hepato-protective, anti-neoplastic, and anti-rheumatic proprieties. In recent years, the investigations of curcumin have been focused on its application to aging and age-associated diseases. Aging is a physiological process in which there is a decreasing of cellular function due to internal or external stimuli. Oxidative stress is one of the most important causes of aging and age-related diseases. Moreover, many age-related disorders such as cancer, neuroinflammation, and infections are due to a low-grade chronic systemic inflammation. Curcumin acting on different proteins is able to contrast both oxidative stress than inflammation. In the brain, curcumin is able to modulate inflammation induced by microglia. Finally in brain tumors curcumin is able to reduce tumor growth by inhibition of telomerase activity. This review emphasizes the anti-aging role of curcumin focusing on its mechanism to counteract aging in the brain. Moreover, new formulations to increase the bioavailability of curcumin are discussed

Methods and pharmaceutical compositions for the cardioprotection

The present invention relates to methods and pharmaceutical compositions for cardioprotection of subjects who experienced a myocardial infarction. In particular, the present invention relates to a ligand of the sonic hedgehog signaling pathway for use in the cardioprotection of a subject who experienced a myocardial infarction

Microparticles Harboring Sonic Hedgehog Morphogen Improve the Vasculogenesis Capacity of Endothelial Progenitor Cells Derived from Myocardial Infarction Patients.

Endothelial progenitor cells (EPC) play a role in endothelium integrity maintenance and regeneration. Decreased numbers of EPC or their impaired function correlates with an increase in cardiovascular events. Thus, EPC are important predictors of cardiovascular mortality and morbidity. Microparticles carrying Sonic hedgehog (Shh) morphogen (MPShhþ) trigger pro-angiogenic responses, both in endothelial cells and in ischaemic rodent models. Here, we propose that MPShhþ regulates EPC function, thus enhancing vasculogenesis, and correcting the defects in dysfunctional EPC obtained from acute myocardial infarction (AMI) patients

Polyphenolic compounds from Clusiaceae plants modulating angiogenesis and vascular endothelium

Polyphenolic compounds have created an increasing interest for their potency about cardiovascular diseases for several years1-2. Nevertheless, most of this research had been focused on polyphenolic compound such as flavanols (e.g. catechine from tea), anthocyanin (e.g. delphinidin from blueberry) and stilbenoides (e.g. resveratrol from grape).The present study was designed to screen the potent effect of polyphenolic compounds isolated from plants belonging to Clusiaceae family on endothelium. A huge number of polyphenols such as xanthones and coumarines have been identified from those species and some of them exhibiting various biological activities such as anti-inflammatory and antioxidant properties3-4. Their effect on endothelium, more particularly on angiogenesis, is not yet well-known. Firstly, we assessed the capacity of six molecules to induce endothelium-dependent relaxation in mice aortic rings involving nitric oxide production. Isocalolongic acid (A1) and 2-deprenylrheediaxanthone (A2) are able to increase NO production on endothelial cells and to induce endothelium-dependant relaxation. Then, we investigated the effects of these compounds on in vitro and ex vivo angiogenesis. We showed that A1 treatment promoted the formation of capillary-like network contrary to A2. Endothelial cell adhesion, migration and proliferation were decreased in presence of A2 whereas endothelial migration and proliferation were improved with A1 treatment. We could explain these results with the capacity of A1 to increase VEGF expression and for A2, to decrease ICAM-1 expression. Thus, the strategy used for the screening allows the detection of active molecules from Clusiaceae family that might be of therapeutic benefit in cardiovascular diseases5