Elsevier

Progress in Cardiovascular Diseases

Volume 61, Issues 3–4, September–October 2018, Pages 328-335
Progress in Cardiovascular Diseases

Precise Therapy for Thoracic Aortic Aneurysm in Marfan Syndrome: A Puzzle Nearing Its Solution

https://doi.org/10.1016/j.pcad.2018.07.020Get rights and content
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Abstract

Marfan Syndrome (MFS) is a rare connective tissue disorder, resulting from mutations in the fibrillin-1 gene, characterized by pathologic phenotypes in multiple organs, the most detrimental of which affects the thoracic aorta. Indeed, thoracic aortic aneurysms (TAA), leading to acute dissection and rupture, are today the major cause of morbidity and mortality in adult MFS patients. Therefore, there is a compelling need for novel therapeutic strategies to delay TAA progression and counteract aortic dissection occurrence. Unfortunately, the wide phenotypic variability of MFS patients, together with the lack of a complete genotype-phenotype correlation, have represented until now a barrier hampering the conduction of translational studies aimed to predict disease prognosis and drug discovery. In this review, we will illustrate available therapeutic strategies to improve the health of MFS patients. Starting from gold standard surgical overtures and the description of the main pharmacological approaches, we will comprehensively review the state-of-the-art of in vivo MFS models and discuss recent clinical pharmacogenetic results. Finally, we will focus on induced pluripotent stem cells (iPSC) as a technology that, if integrated with preclinical research and pharmacogenetics, could contribute in determining the best therapeutic approach for each MFS patient on the base of individual differences. Finally, we will suggest the integration of preclinical studies, pharmacogenetics and iPSC technology as the most likely strategy to help solve the composite puzzle of precise medicine in this condition.

Abbreviations and Acronyms

ACEi
angiotensin converting enzyme inhibitors
ARBs
angiotensin II receptor type 1 blockers
βBs
beta blockers
BP
blood pressure
CCB
calcium channel blockers
CV
cardiovascular
CVD
cardiovascular disease
DN
dominant negative
ECM
extracellular matrix
ESC
embryonic stem cells
FBN1
fibrillin 1
HI
haploinsufficient
iPSC
induced pluripotent stem cell
MFS
Marfan Syndrome
MMPs
matrix metalloproteinases
NC
neural crest
PEARS
personalized external aortic root support
SMC
smooth muscle cells
TAA
thoracic aortic aneurysm
TGF-β
transforming growth factor β
TRR
total root replacement
VSRR
valve-sparing root replacement

Keywords

Marfan syndrome
TAA
FBN1
Pharmacogenetics
iPSC

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Statement of Conflict of Interest: see page 333.

1

These authors contributed equally to this work.