Protease-activated receptor-1 contributes to cardiac remodeling and hypertrophy.

Background: Protease-activated receptor-1 (PAR-1) is the high-affinity receptor for the coagulation protease thrombin. It is expressed by a variety of cell types in the heart, including cardiomyocytes and cardiac fibroblasts. We have shown that tissue factor (TF) and thrombin contribute to infarct size after cardiac ischemia-reperfusion (I/R) injury.

Inhibition of Toll-like receptor 4 with eritoran attenuates myocardial ischemia-reperfusion injury.

Background: We previously reported that the functional mutation of Toll-like receptor 4 (TLR4) in C3H/HeJ mice subjected to myocardial ischemia-reperfusion (MI/R) injury resulted in an attenuation of myocardial infarction size. To investigate the ligand-activating TLR4 during MI/R injury, we evaluated the effect of eritoran, a specific TLR4 antagonist, on MI/R injury, with the goal of defining better therapeutic options for MI/R injury.

Methods And Results: C57BL/6 mice received eritoran (5 mg/kg) intravenously 10 minutes before 30 minutes of in situ of transient occlusion of the left anterior descending artery, followed by 120 minutes of reperfusion.

Specific inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates vascular proliferation in monocrotaline-induced pulmonary hypertension in rats.

Objectives: p38 mitogen-activated protein kinase is associated with many clinical entities characterized by inflammation. We postulated that inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates inflammation and the development of pulmonary hypertension in monocrotaline-treated rats.

Methods: Rats were divided into 4 groups: (1) the control group (daily 0.

FR167653 diminishes infarct size in a murine model of myocardial ischemia-reperfusion injury.

Objective: During myocardial ischemia-reperfusion injury, p38 mitogen-activated protein kinase is activated. We examined the effect of a highly specific inhibitor of p38 mitogen-activated protein kinase, FR167653, in an experimental model of regional myocardial ischemia-reperfusion.

Methods: CD-1 mice received FR167653 intraperitoneally 24 hours before 30 minutes of transient occlusion of the left anterior descending artery, followed by 120 minutes of reperfusion.

Toll-like receptor 4 mediates ischemia/reperfusion injury of the heart.

Background: Restoration of blood flow to the ischemic heart may paradoxically exacerbate tissue injury (ischemia/reperfusion injury). Toll-like receptor 4, expressed on several cell types, including cardiomyocytes, is a mediator of the host inflammatory response to infection. Because ischemia/reperfusion injury is characterized by an acute inflammatory reaction, we investigated toll-like receptor 4 activation in a murine model of regional myocardial ischemia/reperfusion injury.

HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts.

We investigated the role of inducible heat shock proteins 70.1 and 70.3 (HSP70.

Tissue factor and thrombin mediate myocardial ischemia-reperfusion injury.

Reperfusion of the ischemic heart is necessary to prevent irreversible injury of the myocardium, which leads to permanent organ dysfunction. However, reperfusion in itself leads to myocardial ischemia/reperfusion (I/R) injury, which is characterized by an acute inflammatory response mediated by activated inflammatory cells, chemokines, cytokines, and adhesion molecules. The molecular mechanisms of myocardial I/R injury are not completely known.

Systemic consequences of ventricular assist devices: alterations of coagulation, immune function, inflammation, and the neuroendocrine system.

Implantable ventricular assist devices have proven efficacious as a bridge to transplantation and as a bridge to recovery. Although current indications for use of assist devices are somewhat limited, they are likely to expand in the upcoming years, including their use as destination therapy for end-stage heart failure. Recipients of assist devices, however, are prone to certain device-specific complications, including excessive postoperative bleeding, late propensity for thromboembolism, infections, and systemic inflammation, which may contribute to end-organ dysfunction.