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

Peter Matt, Jennifer Habashi, Thierry Carrel, Duke E. Cameron, Jennifer E. Van Eyk, Harry C Dietz

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)389-394
Number of pages6
JournalJournal of Thoracic and Cardiovascular Surgery
Volume135
Issue number2
DOIs
StatePublished - Feb 2008

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Marfan Syndrome
Losartan
Transforming Growth Factor beta
Connective Tissue
Dilatation
Angiotensin II Type 1 Receptor Blockers
Haploinsufficiency
Mitral Valve Prolapse
Primary Prevention
Neutralizing Antibodies
Lung Diseases
Extracellular Matrix
Disease Progression
Dissection
Skeletal Muscle
Hypertension
Morbidity
Mutation
Mortality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

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.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 135, No. 2, 02.2008, p. 389-394.

Research output: Contribution to journalArticle

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