Arginase Inhibition Reverses Endothelial Dysfunction, Pulmonary Hypertension, and Vascular Stiffness in Transgenic Sickle Cell Mice.

Background: In sickle cell disease (SCD), hemolysis results in the release and activation of arginase, an enzyme that reciprocally regulates nitric oxide (NO) synthase activity and thus, NO production. Simply supplementing the common substrate L-arginine, however, fails to improve NO bioavailability. In this study, we tested the hypothesis that arginase inhibition would improve NO bioavailability and thereby attenuate systemic and pulmonary vascular endothelial dysfunction in transgenic mice with SCD.

Role of tissue transglutaminase in age-associated ventricular stiffness.

Aging is associated with increased cardiomyocyte loss, left-ventricular hypertrophy, and the accumulation of extracellular matrix, which results in declining cardiac function. The role of the matrix crosslinking enzyme, tissue transglutaminase (TG2), in age-related myocardial stiffness, and contractile function remains incompletely understood. In this study, we examined the role of TG2 in cardiac function, and determined whether TG2 inhibition can prevent age-associated changes in cardiac function.

Use of nonsteroidal anti-inflammatory drugs in patients with cardiovascular disease: a cautionary tale.

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit production of prostaglandins by acting on cyclooxygenase (COX) isoenzymes 1 and 2. Nonselective NSAIDs inhibit both COX 1 and 2 isoenzymes (eg, ibuprofen and naproxen). Selective NSAIDs act on COX-1 (eg, aspirin) or COX-2 (eg, celecoxib) isoenzymes, respectively.

Elevated uric acid levels predict allograft vasculopathy in cardiac transplant recipients.

Background: Cardiac allograft vasculopathy (CAV) poses the greatest threat to the long-term survival of cardiac transplant recipients, and these individuals often exhibit elevated levels of uric acid (UA), a stimulator of T cells. We hypothesized that hyperuricemia is associated with CAV in cardiac transplant recipients.

Methods: UA levels were measured in cardiac transplant recipients between January 2003 and January 2005.