Cardiovascular research
-
Cardiovascular research · Feb 2004
ReviewPoly(ADP-ribose) polymerase activation in the reperfused myocardium.
The activation of poly(ADP-ribose) polymerase (PARP) is now considered a final common effector in various types of tissue injury including systemic inflammation, circulatory shock and ischemia/reperfusion. Free radical and oxidant production and related cytotoxicity during ischemia/reperfusion leads to DNA strand breakage which activates the nuclear enzyme PARP and initiates an energy-consuming, inefficient cellular metabolic cycle with transfer of the ADP-ribosyl moiety of NAD+ to protein acceptors. During the last 5 years, a growing number of experimental studies demonstrated the beneficial effects of PARP inhibition in cell cultures through rodent models and more recently in pre-clinical large animal models of regional and global ischemia/reperfusion injury. The objective of the current review is to provide an overview of the experimental evidence implicating PARP as a pathophysiological modulator of myocardial injury in vitro and in vivo.
-
Cardiovascular research · Dec 2003
Serotonin receptor antagonist inhibits monocrotaline-induced pulmonary hypertension and prolongs survival in rats.
It has been reported that serotonin (5-HT) is involved in the development of pulmonary arterial hypertension (PAH) with pulmonary vascular remodeling. The purpose of the present study was to examine the role of a 5-HT2A receptor antagonist, sarpogrelate hydrochroride, in preventing or reversing monocrotaline (MCT)-induced PAH in rats. ⋯ Specific 5-HT2A receptor blockade with sarpogrelate immediately after MCT inhibited PAH and prolongs survival in rats. These effects were accompanied by anti-inflammatory and anti-proliferative effects in the lung tissue and marked improvement of pulmonary vascular endothelial dysfunction and activation.
-
Cardiovascular research · Nov 2003
Basal nitric oxide modulates vascular effects of a peptide activating protease-activated receptor 2.
Protease-activated receptor 2 (PAR2) is a G-protein-coupled receptor proteolytically activated by trypsin, tryptase or factor Xa. Alternatively, PAR2 can be activated by synthetic peptides whose sequence mimics the tethered ligand exposed after receptor cleavage. It is known that PAR2 modulates vascular reactivity, both in vitro and in vivo. The present study was designed to investigate the role of basal nitric oxide and cyclic nucleotides, adenosine 3'5'cyclic monophosphate (cAMP) and guanosine 3'5' cyclic monophosphate (cGMP), in the vasorelaxation induced by a PAR2-activating peptide (PAR2-AP; SLIGRL-NH(2)) on rat aorta in vitro. ⋯ Our results suggest that vasorelaxation induced by PAR2-AP is modulated by basal nitric oxide with an involvement of both cyclic nucleotides, cGMP and cAMP.
-
Severe infection and inflammation almost invariably lead to hemostatic abnormalities, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation (DIC). Systemic inflammation results in activation of coagulation, due to tissue factor-mediated thrombin generation, downregulation of physiological anticoagulant mechanisms, and inhibition of fibrinolysis. ⋯ Apart from the general coagulation response to inflammation associated with severe infection, specific infections may cause distinct features, such as hemorrhagic fever or thrombotic microangiopathy. The relevance of the cross-talk between inflammation and coagulation is underlined by the promising results in the treatment of severe systemic infection with modulators of coagulation and inflammation.
-
Sepsis is one of the major causes of mortality in critically ill patients and develops as a result of the host response to infection. A complex network of events is set into motion in the body by the infection and results in the pathogenesis of sepsis. This review article focuses on the molecular mechanisms and components involved in the pathogenesis of sepsis with a major emphasis on the endothelium. This includes sepsis-inducing bacterial components (e.g. endotoxins), cellular targets of these molecules and their responses, host reactions, intracellular and cytokine networks, individual susceptibility and new therapeutic targets in sepsis treatment.