Pathophysiology and Management of Cardiovascular Manifestations in Marfan and Loeys-Dietz Syndromes.

Abstract

Marfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue that affects the cardiovascular, skeletal, ocular, pulmonary, and nervous systems and is usually caused by mutations in the FBN1 gene, which encodes fibrillin-1. MFS is traditionally considered to result from the structural weakness of connective tissue. However, recent investigations on molecular mechanisms indicate that increased transforming growth factor-β (TGF-β) activity plays a crucial role in the pathogenesis of MFS and related disorders, such as Loeys-Dietz syndrome (LDS), which is caused by mutation in TGF-β signaling-related genes. In addition, recent studies show that angiotensin II type 1 receptor (AT1R) signaling enhances cardiovascular pathologies in MFS, and the angiotensin II receptor blocker losartan has the potential to inhibit aortic aneurysm formation. However, the relationship between TGF-β and AT1R signaling pathways remains poorly characterized. In this review, we discuss the recent studies on the molecular mechanisms underlying cardiovascular manifestations of MFS and LDS and the ensuing strategies for management.

• Authors: Norifumi Takeda, Hiroki Yagi, Hironori Hara, Takayuki Fujiwara, Daishi Fujita, Kan Nawata, Ryo Inuzuka, Yuki Taniguchi, Mutsuo Harada, Haruhiro Toko, Hiroshi Akazawa, Issei Komuro
• Journal: International heart journal (Int Heart J) Vol. 57 Issue 3 Pg. 271-7 (May 25 2016) ISSN: 1349-3299 [Electronic] Japan
• PMID: 27181042 (Publication Type: Journal Article, Review)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• FBN1 protein, human
• Fibrillin-1
• Transforming Growth Factor beta
• Losartan

Topics

• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Aortic Aneurysm (etiology, metabolism, physiopathology, prevention & control)
• Disease Management
• Fibrillin-1 (genetics)
• Humans
• Loeys-Dietz Syndrome (complications, drug therapy, genetics, physiopathology)
• Losartan (pharmacology)
• Marfan Syndrome (complications, drug therapy, genetics, physiopathology)
• Signal Transduction (drug effects, genetics)
• Transforming Growth Factor beta (metabolism)