title: 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.affiliation: Department of Cardiovascular Medicine, The University of Tokyo Hospital.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Takeda
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yagi
authors.forename: Hironori
authors.initials: H
authors.lastname: Hara
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Daishi
authors.initials: D
authors.lastname: Fujita
authors.forename: Kan
authors.initials: K
authors.lastname: Nawata
authors.forename: Ryo
authors.initials: R
authors.lastname: Inuzuka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Harada
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Toko
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akazawa
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001014:Aortic Aneurysm / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D019468:Disease Management; D000071838:Fibrillin-1 / Q000235:genetics*; D006801:Humans; D055947:Loeys-Dietz Syndrome / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology*; D008382:Marfan Syndrome / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D054392:Adipokines
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000071838:Fibrillin-1; D019808:Losartan; D016212:Transforming Growth Factor beta; C000605722:FBN1 protein, human; D054392:Adipokines