Recent advances in understanding Marfan syndrome: should we now treat surgical patients with losartan?

Matt, Peter; Habashi, Jennifer; Carrel, Thierry; Cameron, Duke E; Van Eyk, Jennifer E; Dietz, Harry C (2008). Recent advances in understanding Marfan syndrome: should we now treat surgical patients with losartan? Journal of thoracic and cardiovascular surgery, 135(2), pp. 389-94. St. Louis, Mo.: Mosby 10.1016/j.jtcvs.2007.08.047

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OBJECTIVE: Marfan syndrome is a systemic connective tissue disorder caused by mutations in the fibrillin-1 gene. It was originally believed that Marfan syndrome results exclusively from the production of abnormal fibrillin-1 that leads to structurally weaker connective tissue when incorporated into the extracellular matrix. This effect seemed to explain many of the clinical features of Marfan syndrome, including aortic root dilatation and acute aortic dissection, which represent the main causes of morbidity and mortality in Marfan syndrome. METHODS: Recent molecular studies, most based on genetically defined mouse models of Marfan syndrome, have challenged this paradigm. These studies established the critical contribution of fibrillin-1 haploinsufficiency and dysregulated transforming growth factor-beta signaling to disease progression. RESULTS: It seems that many manifestations of Marfan syndrome are less related to a primary structural deficiency of the tissues than to altered morphogenetic and homeostatic programs that are induced by altered transforming growth factor-beta signaling. Most important, transforming growth factor-beta antagonism, through transforming growth factor-beta neutralizing antibodies or losartan (an angiotensin II type 1 receptor antagonist), has been shown to prevent and possibly reverse aortic root dilatation, mitral valve prolapse, lung disease, and skeletal muscle dysfunction in a mouse model of Marfan syndrome. CONCLUSION: There are indicators that losartan, a drug widely used to treat arterial hypertension in humans, offers the first potential for primary prevention of clinical manifestations in Marfan syndrome.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiovascular Surgery

UniBE Contributor:

Carrel, Thierry

ISSN:

0022-5223

ISBN:

18242274

Publisher:

Mosby

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:05

Last Modified:

04 May 2014 23:20

Publisher DOI:

10.1016/j.jtcvs.2007.08.047

PubMed ID:

18242274

Web of Science ID:

000252830400023

URI:

https://boris.unibe.ch/id/eprint/28295 (FactScience: 119574)

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