Cardiovascular research
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Cardiovascular research · Jul 2009
Parstatin: a cryptic peptide involved in cardioprotection after ischaemia and reperfusion injury.
Thrombin activates protease-activated receptor 1 by proteolytic cleavage of the N-terminus. Although much research has focused on the activated receptor, little is known about the 41-amino acid N-terminal peptide (parstatin). We hypothesized that parstatin would protect the heart against ischaemia-reperfusion injury. ⋯ A single treatment of parstatin administered prior to ischaemia confers immediate cardioprotection by recruiting the Gi-protein activation pathway including p38 MAPK, ERK1/2, NOS, and K(ATP) channels. Parstatin exerts effects on both the cardiomyocytes and the coronary circulation to induce cardioprotection. This suggests a potential therapeutic role of parstatin in the treatment of cardiac injury resulting from ischaemia and reperfusion.
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Cardiovascular research · Jul 2009
The targeting of cyclophilin D by RNAi as a novel cardioprotective therapy: evidence from two-photon imaging.
An opening of the mitochondrial permeability transition pore (MPTP), which leads to the loss of mitochondrial membrane potential (DeltaPsi(m)), is the earliest event that commits cells to death, and this process is potentially a prime target for therapeutic intervention against myocardial ischaemia/reperfusion. We aimed to investigate the protective effects of RNA interference (RNAi)-mediated gene silencing of cyclophilin D (CypD), one of the putative components of the MPTP, against myocardial ischaemia/reperfusion using two-photon laser scanning microscopy. ⋯ Therapeutic interventions designed to inactivate CypD may be a promising strategy for reducing cardiac injury against myocardial ischaemia/reperfusion. The two-photon imaging technique provides deeper insight into cardioprotective therapy that targets mitochondria.
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Cardiovascular research · Mar 2009
Role of activated endocannabinoid system in regulation of cellular cholesterol metabolism in macrophages.
Evidence from recent studies suggests that the endocannabinoid system participates in the regulation of lipid metabolism and body composition. We hypothesize that the system is activated by oxidized low-density lipoprotein (oxLDL) and regulates cellular cholesterol metabolism in macrophages. ⋯ We have demonstrated, for the first time, that the endocannabinoid system in macrophages is activated by oxLDL and that the activated endocannabinoid system promotes cellular cholesterol accumulation in macrophages. The results also indicate that selectively blocking the CB1 receptor can reduce oxLDL accumulation in macrophages, which might represent a promising therapeutic strategy for atherosclerosis.
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Cardiovascular research · Jan 2009
Delayed recovery of intracellular acidosis during reperfusion prevents calpain activation and determines protection in postconditioned myocardium.
Indirect data suggest that delayed recovery of intracellular pH (pHi) during reperfusion is involved in postconditioning protection, and calpain activity has been shown to be pH-dependent. We sought to characterize the effect of ischaemic postconditioning on pHi recovery during reperfusion and on calpain-dependent proteolysis, an important mechanism of myocardial reperfusion injury. ⋯ These results provide direct evidence that postconditioning protection depends on prolongation of intracellular acidosis during reperfusion and indicate that inhibited calpain activity could contribute to this protection.
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Cardiovascular research · Sep 2008
G12/13 and Gq mediate S1P2-induced inhibition of Rac and migration in vascular smooth muscle in a manner dependent on Rho but not Rho kinase.
The lysophospholipid mediator sphingosine-1-phosphate (S1P) activates G protein-coupled receptors (GPCRs) to induce potent inhibition of platelet-derived growth factor (PDGF)-induced Rac activation and, thereby, chemotaxis in rat vascular smooth muscle cells (VSMCs). We explored the heterotrimeric G protein and the downstream mechanism that mediated S1P inhibition of Rac and cell migration in VSMCs. ⋯ These observations together suggest that S1P(2) mediates inhibition of Rac and migration through the coordinated action of G(12/13) and G(q) for Rho activation in VSMCs.