Fibrinogen binding to histones in circulation protects against adverse cellular and clinical outcomes.

Background: Circulating histones are released by extensive tissue injury or cell death and play important pathogenic roles in critical illnesses. Their interaction with circulating plasma components and the potential roles in the clinical setting are not fully understood.

Objectives: We aimed to characterize the interaction of histones with fibrinogen and explore its roles in vitro, in vivo, and in patient samples.

Synthesis and Biological Evaluation of Cyclobutane-Based β3 Integrin Antagonists: A Novel Approach to Targeting Integrins for Cancer Therapy.

The Arg-Gly-Asp (RGD)-binding family of integrin receptors, and notably the β3 subfamily, are key to multiple physiological processes involved in tissue development, cancer proliferation, and metastatic dissemination. While there is compelling preclinical evidence that both αvβ3 and αIIbβ3 are important anticancer targets, most integrin antagonists developed to target the β3 integrins are highly selective for αvβ3 or αIIbβ3. We report the design, synthesis, and biological evaluation of a new structural class of ligand-mimetic β3 integrin antagonist.

A functional XPNPEP2 promoter haplotype leads to reduced plasma aminopeptidase P and increased risk of ACE inhibitor-induced angioedema.

Angiotensin I-converting enzyme inhibitors (ACEi) are widely used antihypertensive agents that are associated with a potentially life-threatening reaction, ACEi-angioedema. Impaired metabolism of bradykinin and des-Arg(9) -bradykinin by aminopeptidase P (APP) is a key contributor to ACEi-angioedema. This study aimed to characterize the genetic regulation of the XPNPEP2 gene and identify the genetic factors contributing to variance in plasma APP activity and ACEi-angioedema.

Role of fibrin structure in thrombosis and vascular disease.

Fibrin clot formation is a key event in the development of thrombotic disease and is the final step in a multifactor coagulation cascade. Fibrinogen is a large glycoprotein that forms the basis of a fibrin clot. Each fibrinogen molecule is comprised of two sets of Aα, Bβ, and γ polypeptide chains that form a protein containing two distal D regions connected to a central E region by a coiled-coil segment.

The bradykinin-degrading aminopeptidase P is increased in women taking the oral contraceptive pill.

Introduction: The renin-angiotensin and kininogen-kinin hormonal systems are critically involved in regulating blood pressure and are candidates in contributing to oral contraceptive pill (OCP)-induced hypertension. Angiotensin-converting enzyme (ACE) and aminopeptidase P (AP-P) are key enzymes in these systems and are both involved in the degradation of the vasodilator bradykinin.

Methods: Circulating ACE and AP-P levels were measured by activity assay using selective fluorogenic peptide substrates in plasma samples from the Leeds Family Study.