title: Current and future pharmacological treatment strategies with regard to aortic disease in Marfan syndrome.
abstract: BACKGROUND
  Marfan syndrome is a multisystemic connective tissue disorder caused mainly by mutations in the fibrillin-1 gene. The entire cardiovascular system is affected in patients with Marfan syndrome. Aortic root dilatation, aortic valve regurgitation or - the most feared and life-threatening symptom - aortic root dissection are the most common manifestations. Therapeutic strategies, such as prophylactic aortic root surgery and pharmacological therapy, focus on the prevention of aortic dissection. Currently, the standard medicinal treatments targeting aortic dilatation and dissection consist of agents generally used to lower blood pressure and/or the inotropic state of the heart. By these means, the cyclic repetitive forces exerted on the aortic wall are diminished and thus the onset of aortic dilatation is potentially prevented. Although these pharmacological agents may offer some benefit in reduction of aortic aneurysm expansion rate, they do not target the underlying cause of the progressive aortic degradation.
  
  
  METHODS
  This review discusses the effectiveness of frequently prescribed medications used to prevent and delay aortic complications in Marfan syndrome. New insights on the biochemical pathways leading to aortic disease are also discussed to highlight new targets for pharmacological therapy.
  
  
  CONCLUSIONS
  Recent insights in the transforming growth factor beta signaling pathway and inflammatory mechanisms in a well-established mouse model of Marfan syndrome, have led to studies exploring new pharmacological treatment strategies with doxycycline, statins and angiotensin II receptor blockers. Pharmacological therapy is focused more on prevention than on delay of aortic wall pathology in Marfan syndrome. Of the new pharmacological treatment strategies targeting aortic pathology in Marfan syndrome, angiotensin receptor type 1 blockers are promising candidates, with several clinical trials currently ongoing.
authors.affiliation: Academic Medical Center, Department of Cardiology, B2-240, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Hartog
authors.forename: Romy
authors.initials: R
authors.lastname: Franken
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Maarten
authors.initials: M
authors.lastname: Groenink
authors.forename: Barbara J M
authors.initials: BJ
authors.lastname: Mulder
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D008382:Marfan Syndrome / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology