ABSTRACT
In contrast to the relatively ubiquitous angiotensin-converting enzyme (ACE), expression of the mammalian ACE homologue, ACE2, was initially described in the heart, kidney and testis. ACE2 is a type I integral membrane protein with its active site domain exposed to the extracellular surface of endothelial cells and the renal tubular epithelium. Here ACE2 is poised to metabolise circulating peptides which may include angiotensin II, a potent vasoconstrictor and the product of angiotensin I cleavage by ACE. To this end, ACE2 may counterbalance the effects of ACE within the renin-angiotensin system (RAS). Indeed, ACE2 has been implicated in the regulation of heart and renal function where it is proposed to control the levels of angiotensin II relative to its hypotensive metabolite, angiotensin-(1-7). The recent solution of the structure of ACE2, and ACE, has provided new insight into the substrate and inhibitor profiles of these two key regulators of the RAS. As the complexity of this crucial pathway is unravelled, there is a growing interest in the therapeutic potential of agents that modulate the activity of ACE2.
Subject(s)
Carboxypeptidases/metabolism , Peptidyl-Dipeptidase A/metabolism , Amino Acid Sequence , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Binding Sites , Drosophila Proteins/metabolism , Humans , Membrane Glycoproteins/metabolism , Metalloendopeptidases/metabolism , Receptors, Virus/metabolism , Renin-Angiotensin System/physiology , Severe acute respiratory syndrome-related coronavirus/metabolism , Substrate SpecificityABSTRACT
Care gaps, the discrepancy between processes of care recognized as best practice and care provided in usual clinical practice, exist in cardiovascular disease. Knowledge translation, the process of turning best evidence into best practices, has the potential to reduce care gaps. As the national voice for cardiovascular physicians and scientists, the Canadian Cardiovascular Society is committed to knowledge translation. The present article describes how knowledge translation builds on the constructs of continuing medical education and continuing professional development; what can be done to improve knowledge translation; and what the Canadian Cardiovascular Society is currently doing about this.
Subject(s)
Clinical Competence , Education, Medical, Continuing/standards , Problem-Based Learning/standards , Attitude of Health Personnel , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/therapy , Education, Medical, Continuing/trends , Female , Forecasting , Humans , Interprofessional Relations , Male , Ontario , Problem-Based Learning/trends , Quality of Health Care , Societies, MedicalABSTRACT
Assessment of the size of a myocardial infarct is important from a prognostic point of view, given the opportunities for surgical and pharmacological limitation of the process of necrosis. Serial doses of creatine kinase and its isoenzyme MB given every 4 hours for the first 48 hours of the infarct have allowed us to estimate the size of the infarct and to study the kinetics of enzyme liberation during necrosis. Unknown factors limit the sensitivity of this means of assessing the size of an infarct. The kinetic study showed that the enzyme is liberated by differing mechanisms.