التفاصيل البيبلوغرافية
| العنوان: |
AKAP‐mediated regulation of extracellular matrix secretion in cardiac fibrosis |
| المؤلفون: |
Paterek, Aleksandra, Delaunay, Marion, Kaiser, Simon, Gautschi, Ivan, Diviani, Dario |
| المصدر: |
The FASEB Journal ; volume 36, issue S1 ; ISSN 0892-6638 1530-6860 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2022 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
Cardiac fibroblasts represent the most abundant cell type in the myocardium and provide structural support through controlled proliferation and extracellular matrix (ECM) turnover. In response to chronic pressure overload, quiescent resident cardiac fibroblasts undergo transdifferentiation to myofibroblasts. These activated fibroblasts display increased ECM synthetic capacity and secrete large amounts of collagens. Excessive deposition of ECM results in massive interstitial fibrosis, which decreases myocardial compliance and affects electrical coupling between cardiomyocytes, causing diastolic dysfunctions and arrhythmias. In this context, deciphering the molecular mechanisms favouring increased ECM secretion and deposition in stressed hearts might be the key for the development of targeted approaches inhibiting excessive myocardial fibrosis and dysfunction. A‐kinase anchoring proteins (AKAPs) are molecular scaffolds that act as signal organizers. By recruiting and coordinating the activity of signalling enzymes in space and time they control physiological and pathological responses in cardiac cells. In this respect, our current findings suggest that AKAPs directly regulate the activity of the pathway that controls intracellular ECM protein transport and secretion in myofibroblasts. We are currently evaluating the use of molecular disruptors of selected AKAP complexes to reduce collagen secretion. These disruptors will be tested for their ability to prevent fibrosis and myocardial dysfunction in response to pressure overload. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1096/fasebj.2022.36.s1.r3378 |
| الاتاحة: |
http://dx.doi.org/10.1096/fasebj.2022.36.s1.r3378 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: |
edsbas.3DBAC4C7 |
| قاعدة البيانات: |
BASE |