XIII, plasma transglutaminase). The amount of crosslinked a2-PI is proportional to the amount of a2PI present at the time of clotting. Plasma from a patient with congenital deficiency of a2PI was supplemented with various amounts of purified a2PI. Clots were prepared from these plasmas and were suspended in plasma containing a normal concentration of a2PI, and spontaneous clot lysis was observe...

In diabetic patients, the risk of fracture is high because of impaired bone formation. However, the details of the mechanisms in the development of diabetic osteoporosis remain unclear. In the current study, we investigated the role of plasminogen activator inhibitor (PAI)-1 in the pathogenesis of type 1 diabetic osteoporosis by using PAI-1-deficient mice. Quantitative computed tomography analy...

Adipose-produced pro-inflammatory cytokines contribute to obesity and cancer. This 2x2 experiment was designed to investigate effects of monocyte chemotactic protein-1 (MCP-1) deficiency on pulmonary metastasis of Lewis lung carcinoma (LLC) in MCP-1 deficient and wild-type mice fed a modified AIN93G diet containing 16% and 45% of energy from corn oil, respectively. The high-fat diet significant...

Long-term use of glucocorticoids (GCs) causes numerous adverse effects, including glucose/lipid abnormalities, osteoporosis, and muscle wasting. The pathogenic mechanism, however, is not completely understood. In this study, we used plasminogen activator inhibitor-1 (PAI-1)-deficient mice to explore the role of PAI-1 in GC-induced glucose/lipid abnormalities, osteoporosis, and muscle wasting. C...

OBJECTIVE A single kindred in North America with venous thrombosis was described as having defective fibrinolysis because of increased levels of plasminogen activator inhibitor-1 (PAI-1). Our study describes the discovery of protein S deficiency in this kindred and its association with venous thromboembolism. DESIGN A family study. SETTING Community. PARTICIPANTS Twenty-eight adults (ages...

BACKGROUND Epidemiological and histological evidence implicates proteinases of the matrix metalloproteinase (MMP) family in atherosclerosis and aneurysm formation. We previously indicated a role for urokinase-type plasminogen activator in atherosclerotic media destruction by proteolytic activation of MMPs. However, the role of specific MMPs, such as MMP-9 and MMP-12, in atherosclerosis remains ...

Angiotensin II causes cardiovascular injury in part by aldosterone-induced mineralocorticoid receptor activation, and it can also activate the mineralocorticoid receptor in the absence of aldosterone in vitro. Here we tested whether endogenous aldosterone contributes to angiotensin II/salt-induced cardiac, vascular, and renal injury by the mineralocorticoid receptor. Aldosterone synthase knocko...

A family with a history of severe recurrent venous thromboembolic disease was studied to determine if a plasma protein deficiency could account for observed disease. Protein S levels in plasma were determined immunologically using the Laurell rocket technique. The propositus, his mother, his aunt, and his cousin who were clinically affected had 17% to 65% of the control levels of protein S anti...

This study describes the binding of plasminogen and tissue-type plasminogen activator (t-PA) to the extracellular matrix proteins fibronectin and laminin. Plasminogen bound specifically and saturably to both fibronectin and laminin immobilized on microtiter wells, with Kd(app) values of 115 and 18 nM, respectively. Limited proteolysis by endoproteinase V8 coupled with ligand blotting analysis s...

Proteins of the plasminogen activation system are broadly expressed throughout the nervous system, and key roles for these proteins in neuronal function have been demonstrated. Recent reports have established that plasminogen is synthesized in neuroendocrine tissues, making this protein and the proteolytic activity of the product of its activation, plasmin, available at sites separated anatomic...