Original research article BACKGROUND: Myocardial fibrosis is a feature of many cardiac diseases. We used proteomics to profile glycoproteins in the human cardiac extracellular matrix (ECM). METHODS:Atrial specimens were analyzed by mass spectrometry after extraction of ECM proteins and enrichment for glycoproteins or glycopeptides.RESULTS: ECM-related glycoproteins were identified in left and right atrial appendages from the same patients. Several known glycosylation sites were confirmed. In addition, putative and novel glycosylation sites were detected. On enrichment for glycoproteins, peptides of the small leucine-rich proteoglycan decorin were identified consistently in the flowthrough. Of all ECM proteins identified, decorin was found to be the most fragmented. Within its protein core, 18 different cleavage sites were identified. In contrast, less cleavage was observed for biglycan, the most closely related proteoglycan. Decorin processing differed between human ventricles and atria and was altered in disease. The C-terminus of decorin, important for the interaction with connective tissue growth factor, was detected predominantly in ventricles in comparison with atria. In contrast, atrial appendages from patients in persistent atrial fibrillation had greater levels of full-length decorin but also harbored a cleavage site that was not found in atrial appendages from patients in sinus rhythm. This cleavage site preceded the N-terminal domain of decorin that controls muscle growth by altering the binding capacity for myostatin. Myostatin expression was decreased in atrial appendages of patients with persistent atrial fibrillation and hearts of decorin null mice. A synthetic peptide corresponding to this decorin region dose-dependently inhibited the response to myostatin in cardiomyocytes and in perfused mouse hearts. CONCLUSIONS:This proteomics study is the first to analyze the human cardiac ECM. Novel processed forms of decorin protein core, uncovered in human atrial appendages, can regulate the local bioavailability of antihypertrophic and profibrotic growth factors.glycoproteomics reveals Decorin Peptides With anti-Myostatin activity in human atrial Fibrillation
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: Is perioperative corticosteroid administration associated with a reduced incidence of postoperative atrial fibrillation (POAF) in adult cardiac surgery? A total of 70 papers were identified using the search as described below. Of these, eight were identified to provide best evidence to answer the clinical question. These papers consisted of well-designed, double-blinded randomized control trials (RCTs) or meta-analysis of RCTs that presented sufficient data to reach conclusions regarding the issues of interest for this review. Postoperative atrial fibrillation occurrence, outcomes and complications were included in the assessment. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the papers are tabulated. Literature search showed that the prophylactic use of hydrocortisone (100 mg/day, 4 days) can reduce the incidence of POAF to 30%, compared with 48% in the control group (P = 0.004). One gram of methylprednisolone before surgery followed by 4 mg of dexamethasone every 6 h for 1 day after surgery was also associated with a significant reduction in POAF (21 vs 51%; P = 0.003). Moreover, a single dose of dexamethasone (0.6 mg/kg) can significantly diminish POAF (18.95 vs 32.3%; P = 0.027). The changes in POAF appeared greatest in patients receiving intermediate doses of corticosteroid (50-210 mg of dexamethasone equivalent), while both lower (up to 8 mg) and higher (236-2850 mg) dosing resulted in blunted effects. Similarly, a moderate dose of hydrocortisone (200-1000 mg/day) is as effective as high (1001-10 000 mg/day) and very high doses (10 000 mg/day). Although the optimal dose, dosing interval and duration of therapy are unclear, meta-analysis suggests that a single dose can be as effective as multiple doses. No statistically significant complications associated with the use of corticosteroids were reported in any of the studies. We conclude that a single prophylactic moderate dose of corticosteroid (50-210 mg of dexamethasone equivalent or 200-1000 mg/day hydrocortisone) can significantly reduce the risk of POAF with no significant increase in morbidity or mortality.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.