Therapy insight: aortic aneurysm and dissection in Marfan's syndrome.
Aortic dissection and aneurysm are common clinical problems with life-threatening consequences; they are also the hallmark of several genetic diseases, including Marfan's syndrome (MFS). In spite of clinical and surgical advances that have increased life expectancy for affected patients, cardiovascular manifestations remain significant contributors to morbidity and mortality in MFS. Dissecting aortic aneurysm in this disorder is accounted for by mutations in fibrillin-1, the major component of the microfibrils associated with elastin in the elastic fibers of the aortic media. Genetic studies of human patients and murine models have yielded invaluable insights into the pathophysiology of aneurysm formation and progression in MFS. They have also revealed a previously unappreciated role of microfibrils in regulating transforming growth factor and bone morphogenetic protein signaling. As a result, exciting new hypotheses have emerged regarding the pathogenesis of MFS, as well as opportunities to explore translational applications of this information that may be relevant to various manifestations of the disease.
Ramirez
Francesco
F
Laboratory of Genetics and Organogenesis, Hospital for Special Surgery at the Weill Medical College of Cornell University, 535 East 70th Street, New York, NY 10021, USA. RamirezF@hss.edu
Dietz
Harry C
HC
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000784:Aortic Dissection / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D001014:Aortic Aneurysm / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D018450:Disease Progression; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D008382:Marfan Syndrome / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D020894:Microfibrils / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014656:Vascular Surgical Procedures; D054392:Adipokines
D000319:Adrenergic beta-Antagonists; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D016212:Transforming Growth Factor beta; C000605722:FBN1 protein, human; D054392:Adipokines