Molecular pathogenesis of Marfan syndrome

Ramachandra, Chrishan J A; Mehta, Ashish; Guo, Kenneth; Wong, Philip; Tan, Ju Le; Shim, Winston

doi:10.1016/j.ijcard.2015.03.423

Cited by 57 publications

(51 citation statements)

References 91 publications

(114 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The mutation of this genes can benefit to the AA appearance and progression. For example, the Marfan syndrome has associated with the mutation of FBN1 and the TGF-β activation signal moreover the different position mutation of FBN1 has the different mechanism in the pathogenesis (35).The family genetic examination may have an application prospect to screen AA in individuals who have the family history using PCR amplification. But detection rate for genes mutations in familial AA is <20% and many individuals with family history of AA have normal diameter of aortic.…”

Section: Genesmentioning

confidence: 99%

“…In Marfan syndrome, FBN1 mutations and TGF-β results in an imbalance between MMPs and TIMPs, and these can increase proteolysis in the aortic wall and finally cause AA formation (35,112). Much effort has been made to test therapeutic agents aiming the molecular changes, and an angiotensin receptor blocker has been found to inhibit the effect of TGF-β in the vascular wall (113)(114)(115)(116).…”

Section: Marfan Syndromementioning

confidence: 99%

See 1 more Smart Citation

Molecular targets in aortic aneurysm for establishing novel management paradigms

Zhu

et al. 2017

J. Thorac. Dis.

View full text Add to dashboard Cite

Aortic aneurysm (AA) is a lethal disease and presents a large challenge for surgeons in the clinic.Although surgical management remains the major choice of AA, operative mortality remains high. With advances in understanding of the mechanisms of AAs, molecular targets, such as matrix metalloproteinases (MMPs), D-dimer, and inflammation markers, including C-reactive protein, interleukins and phagocytes, are important in the pathology of development of AA. These markers may become important for improving the diagnostic quality and provide more therapeutic choices for treatment of AA. Although these new markers require long-term trials before they can be translated into the clinic, they can still be helpful in determining new directions. The main aim of this review is to discuss the current findings of molecular targets in progression of AA and discuss the potential application of these new targets for managing this disease.

show abstract

Section: Genesmentioning

confidence: 99%

Section: Marfan Syndromementioning

confidence: 99%

Molecular targets in aortic aneurysm for establishing novel management paradigms

Zhu

et al. 2017

J. Thorac. Dis.

View full text Add to dashboard Cite

show abstract

“…For example, Marfan syndrome is an inherited connective tissue disorder associated with ocular, musculoskeletal and cardiovascular manifestations, characterised by a tall and slender build and disproportionately long limbs, posing potential lethal threat during high-intensity exercise 11. Marfan syndrome results most commonly from mutations in the fibrillin-1 (FBN1) gene on chromosome 15, which encodes for the glycoprotein fibrillin 12. Sporting organisations such as professional basketball and volleyball associations should consider the possibility of Marfan syndrome when conducting preparticipation screening.…”

Section: Genetic Testing For Health-related Purposesmentioning

confidence: 99%

Ethics of genetic testing and research in sport: a position statement from the Australian Institute of Sport

et al. 2016

View full text Add to dashboard Cite

As Australia's peak high-performance sport agency, the Australian Institute of Sport (AIS) has developed this position statement to address the implications of recent advances in the field of genetics and the ramifications for the health and well-being of athletes. Genetic testing has proven of value in the practice of clinical medicine. There are, however, currently no scientific grounds for the use of genetic testing for athletic performance improvement, sport selection or talent identification. Athletes and coaches should be discouraged from using direct-to-consumer genetic testing because of its lack of validation and replicability and the lack of involvement of a medical practitioner in the process. The transfer of genetic material or genetic modification of cells for performance enhancement is gene doping and should not be used on athletes. There are, however, valid roles for genetic research and the AIS supports genetic research which aims to enhance understanding of athlete susceptibility to injury or illness. Genetic research is only to be conducted after careful consideration of a range of ethical concerns which include the provision of adequate informed consent. The AIS is committed to providing leadership in delivering an ethical framework that protects the well-being of athletes and the integrity of sport, in the rapidly changing world of genomic science.

show abstract

“…The FDA has thus recognised QT prolongation as an important variable which needs to be addressed during drug development while the International Conference of Harmonisation (ICH) Expert Working Group (EWG) for drug development has placed risk assessments for delayed ventricular repolarisation as standard procedure of preclinical evaluation of new chemical entities 24 . Cardiomyocytes differentiated from hPSCs open a new paradigm in regenerative medicine 25,26 , disease modelling 20,27 , drug discovery [18][19][20]28 and understanding developmental phenomena 17,29 . Similar to their adult counterparts, hPSC-derived cardiomyocytes express cardiac genes, structural proteins and ion channels 17,30 as well as exhibit a functional excitation-contraction coupling system which could be modulated through β1/β2-adrenergic and muscarinic receptor agonists 31 .…”

Section: Human Pluripotent Stem Cells and Drug Discovery: A New Beginmentioning

confidence: 99%

Human Pluripotent Stem Cells and Drug Discovery: A New Beginning

Verma¹,

Mehta²,

Flora³

2016

Def. Life. Sc. Jl.

View full text Add to dashboard Cite

Human pluripotent stem cells (hPSCs) offer unique opportunities to discover and develop a new generation of drugs. Their ability to differentiate into virtually any cell type renders them a cost-effective, renewable source of tissue-specific cell types capable of predicting human responses towards novel chemical entities. Using these improved in vitro models based on physiologically relevant human cell types could result in identifying highly precise and safe compounds, thereby reducing drug attrition rates. Moreover, ability to develop humanised disease models for patient-stratified drug screening makes hPSCs an impeccable tool in translational medicine. In this mini-review we focus on the positives and negatives of utilising hPSC-derived cell types as drug discovery platforms with special emphasis on cardio-, hepato-and embryotoxicity.

show abstract

Molecular pathogenesis of Marfan syndrome

Cited by 57 publications

References 91 publications

Molecular targets in aortic aneurysm for establishing novel management paradigms

Molecular targets in aortic aneurysm for establishing novel management paradigms

Ethics of genetic testing and research in sport: a position statement from the Australian Institute of Sport

Human Pluripotent Stem Cells and Drug Discovery: A New Beginning

Contact Info

Product

Resources

About