Study to Explore the Association of the Renin-Angiotensin System and Right Ventricular Function in Mechanically Ventilated Patients.

Background: Right ventricular () dysfunction is associated with pulmonary vasoconstriction in mechanically ventilated patients. Enhancing the activity of angiotensin-converting enzyme 2 (2), a key enzyme of the renin-angiotensin system (), using recombinant human 2 (2) could alleviate -mediated vasoconstriction and vascular remodeling.

Methods: This prospective observational study investigated the association between concentrations of peptides (Ang II or Ang(1-7)) and markers of function, as assessed by echocardiography (ratio of to left ventricular end-diastolic area, interventricular septal motion, and pulmonary arterial systolic pressure ()).

An open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of GSK2586881 in participants with pulmonary arterial hypertension.

Preclinical and early clinical studies suggest that angiotensin-converting enzyme type 2 activity may be impaired in patients with pulmonary arterial hypertension (PAH); therefore, administration of exogenous angiotensin-converting enzyme type 2 (ACE2) may be beneficial. This Phase IIa, multi-center, open-label, exploratory, single-dose, dose-escalation study (NCT03177603) assessed the potential vasodilatory effects of single doses of GSK2586881 (a recombinant human ACE2) on acute cardiopulmonary hemodynamics in hemodynamically stable adults with documented PAH who were receiving background PAH therapy. Successive cohorts of participants were administered a single intravenous dose of GSK2586881 of 0.

Effects of Recombinant Human Angiotensin-Converting Enzyme 2 on Response to Acute Hypoxia and Exercise: A Randomised, Placebo-Controlled Study.

Introduction: Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system (RAS) that has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). Enhancing ACE2 activity using GSK2586881, a recombinant form of human ACE2, could be beneficial in diseases such as ARDS but may blunt the hypoxic pulmonary vasoconstriction (HPV) response and potentially impact systemic and tissue oxygenation. This study aimed to evaluate the effect of GSK2586881 0.

Intranasal GSK2245035, a Toll-like receptor 7 agonist, does not attenuate the allergen-induced asthmatic response in a randomized, double-blind, placebo-controlled experimental medicine study.

Background: Allergic asthma is a heterogenous disorder predominantly driven by a type 2 inflammatory response to aeroallergens. Therapeutic modulation to rebalance these type 2 responses may offer clinical benefit for allergic respiratory inflammatory diseases, with the potential for disease modification. GSK2245035, a selective toll-like receptor-7 agonist, preferentially stimulates the induction of type 1 interferon alpha, reducing type 2 responses.

Statin Use is Associated With Insulin Resistance in Participants of the Canadian Multicentre Osteoporosis Study.

Context: Statins have been linked to the development of diabetes and atherosclerotic plaque calcification in patients with cardiac disease.

Objective: To determine the association between statin use and statin characteristics and insulin resistance and abdominal aortic calcification (AAC) in participants of the Canadian Multicentre Osteoporosis Study (CaMos).

Design: Observational study.