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Marfan syndrome: A therapeutic challenge for long-term care
- Source :
- Biochemical pharmacology. 164
- Publication Year :
- 2019
-
Abstract
- Marfan syndrome (MFS) is an autosomal dominant genetic disorder caused by mutations in the fibrillin-1 gene. Acute aortic dissection is the leading cause of death in patients suffering from MFS and consequence of medial degeneration and aneurysm formation. In addition to its structural function in the formation of elastic fibers, fibrillin has a major role in keeping maintaining transforming growth factor β (TGF-β) in an inactive form. Dysfunctional fibrillin increases TGF-β bioavailability and concentration in the extracellular matrix, leading to activation of proinflammatory transcription factors. In turn, these events cause increased expression of matrix metalloproteinases and cytokines that control the migration and infiltration of inflammatory cells into the aorta. Moreover, TGF-β causes accumulation of reactive oxygen species leading to further degradation of elastin fibers. All these processes result in medial elastolysis, which increases the risk of vascular complications. Although MFS is a hereditary disease, symptoms and traits are usually not noticeable at birth. During childhood or adolescence affected individuals present with severe tissue weaknesses, especially in the aorta, heart, eyes, and skeleton. Considering this, even young patients should avoid activities that exert additional stress and pressure on the aorta and the cardiovascular system. Thus, if the diagnosis is made and prophylactic treatment is initiated in a timely fashion, MFS and its preliminary pathophysiologic vascular remodeling can be successfully ameliorated reducing the risk of life-threatening complications. This commentary focuses on new research opportunities and molecular findings on MFS, discusses future challenges and possible long-term therapies.
- Subjects :
- 0301 basic medicine
Marfan syndrome
Adrenergic beta-Antagonists
Disease
Vascular Remodeling
Bioinformatics
Fibrillins
Biochemistry
Muscle, Smooth, Vascular
Proinflammatory cytokine
Marfan Syndrome
03 medical and health sciences
0302 clinical medicine
Transforming Growth Factor beta
medicine.artery
medicine
Humans
Pharmacology
Aortic dissection
Aorta
biology
business.industry
Genetic disorder
medicine.disease
Long-Term Care
Matrix Metalloproteinases
030104 developmental biology
030220 oncology & carcinogenesis
biology.protein
business
Fibrillin
Elastin
Subjects
Details
- ISSN :
- 18732968
- Volume :
- 164
- Database :
- OpenAIRE
- Journal :
- Biochemical pharmacology
- Accession number :
- edsair.doi.dedup.....3589d24b7d6d14fbe0afab0e58a99b5d