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Sex, pregnancy and aortic disease in Marfan syndrome

(2017) PLOS ONE. 12(7).
Author
Organization
Abstract
Background : Sex-related differences as well as the adverse effect of pregnancy on aortic disease outcome are well-established phenomena in humans with Marfan syndrome (MFS). The underlying mechanisms of these observations are largely unknown. Objectives : In an initial (pilot) step we aimed to confirm the differences between male and female MFS patients as well as between females with and without previous pregnancy. We then sought to evaluate whether these findings are recapitulated in a pre-clinical model and performed in-depth cardiovascular phenotyping of mutant male and both nulliparous and multiparous female Marfan mice. The effect of 17 beta-estradiol on fibrillin-1 protein synthesis was compared in vitro using human aortic smooth muscle cells and fibroblasts. Results : Our small retrospective study of aortic dimensions in a cohort of 10 men and 20 women with MFS (10 pregnant and 10 non-pregnant) confirmed that aortic root growth was significantly increased in the pregnant group compared to the non-pregnant group (0.64mm/year vs. 0.12mm/year, p = 0.018). Male MFS patients had significantly larger aortic root diameters compared to the non-pregnant and pregnant females at baseline and follow-up (p = 0.002 and p = 0.007, respectively), but no significant increase in aortic root growth was observed compared to the females after follow-up (p = 0.559 and p = 0.352). In the GT-8/+ MFS mouse model, multiparous female Marfan mice showed increased aortic diameters when compared to nulliparous females. Aortic dilatation in multiparous females was comparable to Marfan male mice. Moreover, increased aortic diameters were associated with more severe fragmentation of the elastic lamellae. In addition, 17 beta-estradiol was found to promote fibrillin-1 production by human aortic smooth muscle cells. Conclusions : Pregnancy-related changes influence aortic disease severity in otherwise protected female MFS mice and patients. There may be a role for estrogen in the female sex protective effect.
Keywords
LEFT-VENTRICULAR FUNCTION, TGFBR2 MUTATIONS, IN-VIVO, ANEURYSM, FIBRILLIN-1, WOMEN, COMPLICATIONS, MICE, ESTROGEN, GROWTH

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MLA
Renard, Marjolijn et al. “Sex, Pregnancy and Aortic Disease in Marfan Syndrome.” PLOS ONE 12.7 (2017): n. pag. Print.
APA
Renard, M., Muiño Mosquera, L., Manalo, E. C., Tufa, S., Carlson, E. J., Keene, D. R., De Backer, J., et al. (2017). Sex, pregnancy and aortic disease in Marfan syndrome. PLOS ONE, 12(7).
Chicago author-date
Renard, Marjolijn, Laura Muiño Mosquera, Elise C Manalo, Sara Tufa, Eric J Carlson, Douglas R Keene, Julie De Backer, and Lynn Y Sakai. 2017. “Sex, Pregnancy and Aortic Disease in Marfan Syndrome.” Plos One 12 (7).
Chicago author-date (all authors)
Renard, Marjolijn, Laura Muiño Mosquera, Elise C Manalo, Sara Tufa, Eric J Carlson, Douglas R Keene, Julie De Backer, and Lynn Y Sakai. 2017. “Sex, Pregnancy and Aortic Disease in Marfan Syndrome.” Plos One 12 (7).
Vancouver
1.
Renard M, Muiño Mosquera L, Manalo EC, Tufa S, Carlson EJ, Keene DR, et al. Sex, pregnancy and aortic disease in Marfan syndrome. PLOS ONE. 2017;12(7).
IEEE
[1]
M. Renard et al., “Sex, pregnancy and aortic disease in Marfan syndrome,” PLOS ONE, vol. 12, no. 7, 2017.
@article{8535966,
  abstract     = {Background : Sex-related differences as well as the adverse effect of pregnancy on aortic disease outcome are well-established phenomena in humans with Marfan syndrome (MFS). The underlying mechanisms of these observations are largely unknown. 
Objectives : In an initial (pilot) step we aimed to confirm the differences between male and female MFS patients as well as between females with and without previous pregnancy. We then sought to evaluate whether these findings are recapitulated in a pre-clinical model and performed in-depth cardiovascular phenotyping of mutant male and both nulliparous and multiparous female Marfan mice. The effect of 17 beta-estradiol on fibrillin-1 protein synthesis was compared in vitro using human aortic smooth muscle cells and fibroblasts. 
Results : Our small retrospective study of aortic dimensions in a cohort of 10 men and 20 women with MFS (10 pregnant and 10 non-pregnant) confirmed that aortic root growth was significantly increased in the pregnant group compared to the non-pregnant group (0.64mm/year vs. 0.12mm/year, p = 0.018). Male MFS patients had significantly larger aortic root diameters compared to the non-pregnant and pregnant females at baseline and follow-up (p = 0.002 and p = 0.007, respectively), but no significant increase in aortic root growth was observed compared to the females after follow-up (p = 0.559 and p = 0.352). In the GT-8/+ MFS mouse model, multiparous female Marfan mice showed increased aortic diameters when compared to nulliparous females. Aortic dilatation in multiparous females was comparable to Marfan male mice. Moreover, increased aortic diameters were associated with more severe fragmentation of the elastic lamellae. In addition, 17 beta-estradiol was found to promote fibrillin-1 production by human aortic smooth muscle cells. 
Conclusions : Pregnancy-related changes influence aortic disease severity in otherwise protected female MFS mice and patients. There may be a role for estrogen in the female sex protective effect.},
  articleno    = {e0181166},
  author       = {Renard, Marjolijn and Muiño Mosquera, Laura and Manalo, Elise C and Tufa, Sara and Carlson, Eric J and Keene, Douglas R and De Backer, Julie and Sakai, Lynn Y},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keywords     = {LEFT-VENTRICULAR FUNCTION,TGFBR2 MUTATIONS,IN-VIVO,ANEURYSM,FIBRILLIN-1,WOMEN,COMPLICATIONS,MICE,ESTROGEN,GROWTH},
  language     = {eng},
  number       = {7},
  pages        = {16},
  title        = {Sex, pregnancy and aortic disease in Marfan syndrome},
  url          = {http://dx.doi.org/10.1371/journal.pone.0181166},
  volume       = {12},
  year         = {2017},
}

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