cytochrome-c-t and Arteriosclerosis

Positive changes were more pronounced in patients with chronic ischemia of the lower limbs treated with energostim alone and in combination with trental in comparison with patients receiving trental monotherapy. The best effect was attained in patients treated with energostim in combination with trental.

Topics: Adult; Aged; Aged, 80 and over; Arteriosclerosis; Coronary Disease; Cytochromes c; Drug Combinations; Echocardiography; Female; Humans; Inosine; Ischemia; Laser-Doppler Flowmetry; Leg; Male; Microcirculation; Middle Aged; NAD; Pentoxifylline

Reactive oxygen species (ROS) are implicated in many disease such as inflammation, arteriosclerosis, cancer. Therefore, a water-soluble cationic metalloporphyrins with SOD activity are studied widely as antioxidant drugs. Further, liposomes are applied to drug delivery system (DDS) as drug carriers and investigated for example disposition and stability. We designed PEG modified liposomes for avoiding reticuloendothelial system (RES) and embedded cationic metalloporphyrins for DDS, evaluated antioxidant and anticancer property. Preservation of these particle size measured DLS in an in vitro system, in order to simulate in vivo conditions of flow. Result of this measurement, we found Pluronic F-68/ liposomes have a long circulation property, and avoid fusion with plasma protein. SOD activity was determined by the stopped-flow analysis and cytochrome c assay, which allowed the evaluation of k(cat) and IC(50) for the reaction with a superoxide anion radical (.O(2)(-)). Anti cancer property was measured by cell viability test. We found that F-68/ liposomes were the most effective catalyst as antioxidant and anticancer. These results revealed that porphyrin-embedded PEG-liposomes had the property of long circulation in blood and that this compound was effective as a SOD model compound with a drug carrier capacity.

Topics: Animals; Antineoplastic Agents; Antioxidants; Arteriosclerosis; Catalysis; Cell Line, Tumor; Cell Survival; Cytochromes c; Drug Screening Assays, Antitumor; Humans; Liposomes; Metalloporphyrins; Neoplasms; Particle Size; Poloxamer; Superoxide Dismutase; Superoxides

Oxidized low-density lipoprotein (oxLDL)-induced apoptosis of vascular endothelial cells may contribute to plaque erosion and rupture. We aimed to clarify the relationship between the oxLDL-induced calcium signal and induction of apoptotic pathways.. Apoptosis was evaluated by biochemical methods, including studies of enzyme activities, protein processing, release of proapoptotic factors, chromatin cleavage, and especially by morphological methods that evaluate apoptosis/necrosis by SYTO-13/propidium iodide fluorescent labeling. The oxLDL-induced sustained calcium rise activated 2 distinct calcium-dependent mitochondrial apoptotic pathways in human microvascular endothelial cells. OxLDLs induced calpain activation and subsequent Bid cleavage and cytochrome C release, which were blocked by calpeptin. Cyclosporin-A inhibited cytochrome C release, possibly by inhibiting the opening of the mitochondrial permeability transition pore (mPTP). Calcineurin, another cyclosporin-sensitive step, was not implicated, because oxLDLs inhibited calcineurin and FK-506 treatment was ineffective. Cytochrome C release in turn induced caspase-3 activation. In addition, oxLDLs triggered release and nuclear translocation of mitochondrial apoptosis-inducing factor through a mechanism dependent on calcium but independent of calpains, mPTP, and caspases.. OxLDL-induced apoptosis involves 2 distinct calcium-dependent pathways, the first mediated by calpain/mPTP/cytochrome C/caspase-3 and the second mediated by apoptosis-inducing factor, which is cyclosporin-insensitive and caspase-independent.

Topics: Apoptosis; Apoptosis Inducing Factor; Arteriosclerosis; BH3 Interacting Domain Death Agonist Protein; Calcium; Calpain; Carrier Proteins; Caspase 3; Caspase Inhibitors; Caspases; Cells, Cultured; Cyclosporine; Cysteine Proteinase Inhibitors; Cytochromes c; Endothelium, Vascular; Flavoproteins; Humans; Immunosuppressive Agents; Lipoproteins, LDL; Membrane Proteins; Microcirculation; Mitochondria; Tacrolimus

Topics: Arteriosclerosis; Atherosclerosis; Cytochromes; Cytochromes c; Humans

Topics: Administration, Intravenous; Arteriosclerosis; Cytochromes; Cytochromes c