Recent advances in understanding Marfan syndrome: should we now treat surgical patients with losartan?
Matt P, Habashi J, Carrel T, Cameron DE, Van Eyk JE, Dietz HC.
Howard Hughes Medical Institute and Johns Hopkins University School of Medicine,
Baltimore, MD 21224, USA.
J Thorac Cardiovasc Surg. 2008 Feb;135(2):389-94.


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.
Marfan syndrome
'Artificial' evolution
Genetic enhancement
Germline genetic engineering
Congenital insensitivity to pain
Mood genes and human nature
Preimplantation genetic diagnosis
A life without pain? Hedonists take note'
'The Principle of Procreative Beneficience'
Gene therapy and performance enhancement
Transhumanism (H+): toward a Brave New World?

and further reading

BLTC Research
Utopian Surgery?
The Good Drug Guide
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
MDMA: Utopian Pharmacology
Critique of Huxley's Brave New World