sirolimus and candesartan

Few multicenter studies have assessed the effects of angiotensin receptor blockers on cardiovascular events after drug-eluting stent implantation in patients with ischemic heart disease.. An open-label multicenter randomized prospective study is in progress to evaluate the effects of candesartan on cardiovascular events in patients with ischemic heart disease after implantation of sirolimus- and/or paclitaxel-eluting stents.. A total of 1,145 patients were enrolled at 39 institutes in the Candesartan for prevention of Cardiovascular events after CYPHER or TAXUS Coronary stenting (4C trial). Patients were randomized into a group treated with candesartan (n=602) and a group treated with standard medical therapy without candesartan (n=543). The primary endpoint of the 4C trial is a composite of all-cause death, successful resuscitation after cardiopulmonary arrest and cardiovascular events including non-fatal myocardial infarction, unstable angina requiring emergent hospitalization, congestive heart failure requiring emergent hospitalization and cerebrovascular attacks. All patients will be followed-up for 36 months.. The 4C trial will be the first multicenter study to elucidate the effects of candesartan after drug-eluting stent implantation and may provide new information to optimize medical therapy after percutaneous coronary interventions.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Biphenyl Compounds; Cardiovascular Diseases; Clinical Protocols; Combined Modality Therapy; Drug Discovery; Drug-Eluting Stents; Female; Humans; Japan; Male; Middle Aged; Myocardial Ischemia; Paclitaxel; Sirolimus; Tetrazoles

Signal transduction of Angiotensin II (Ang II) induced autophagy and its role in Ang II-induced dysfunction of HUVECs are still unclear.. HUVECs are stimulated with different doses of Ang II (10-9-10-5 mol/L) for different time (6-48 hours). Autophagy-related protein markers: LC3, Beclin-1 and SQSTM1/p62 are measured by western blot.. Incubation with Ang II increases autophagic flux (Beclin-1, autophagosomes formation, and degradation of SQSTM1/p62, LC3-I). Increased autophagic levels are inhibited by pretreatment with Ang II type 1 receptor (AT1) blocker (Candesartan), NADPH Oxidase inhibitor (apocycin), mitochondrial K. Our results demonstrate that Ang II stimulation increases autophagy levels via AT1 receptor, NADPH oxidase, mitochondrial K

Topics: Acetophenones; Adenine; Angiotensin II; Animals; Autophagosomes; Autophagy; Autophagy-Related Proteins; Benzimidazoles; Biphenyl Compounds; Decanoic Acids; Human Umbilical Vein Endothelial Cells; Humans; Hydroxy Acids; Models, Biological; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase Type III; Phosphorylation; Signal Transduction; Sirolimus; Tetrazoles; Time Factors

Sirolimus-eluting stents (SES) are widely used in coronary artery disease as revascularization therapy. Although endothelial dysfunction induced by implanted SES can become a major clinical concern, therapeutic strategies to overcome this disorder remain unclear. The aim of the present study was therefore to identify effective therapies in a clinically relevant animal model.. Twenty-one pigs were randomized to control, candesartan (CAN) and candesartan plus pioglitazone (CAN+PIO) groups. Drugs were administered orally for 7 days before SES implantation until the time of death. Forty-two SES were used in porcine coronary arteries. Early inflammatory cell adhesion in SES evaluated on scanning electron microscopy at 3 days was significantly suppressed in the CAN and CAN+PIO groups compared with controls. Bradykinin-induced endothelium-dependent relaxation at an adjacent segment distal to the SES evaluated using organ chambers was reduced compared with intact segments in control coronaries at 28 days. Endothelial dysfunction was reversed by CAN and even more obviously improved in the CAN+PIO group.. Candesartan protected against vascular inflammation and restored endothelial function after SES implantation. The combination of candesartan and pioglitazone was more effective than candesartan monotherapy and might confer vascular protection when administered before SES implantation.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Coronary Vessels; Drug Therapy, Combination; Drug-Eluting Stents; Endothelium, Vascular; Hypoglycemic Agents; Inflammation; Pioglitazone; Protective Agents; Sirolimus; Sus scrofa; Tetrazoles; Thiazolidinediones; Treatment Outcome