Proteomics discovery of novel biomarkers for diagnosis and stratification of patient at risk for atherosclerotic cardiovascular diseases
Atherosclerotic coronary artery disease (CAD)-related deaths will continue to rise along with global population ageing. Although established conventional risk factors are in place for the prediction of cardiovascular (CV) events, however, the absence does not necessarily imply zero CAD risk. Effe...
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| Format: | Thesis |
| Language: | English |
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2017
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| Online Access: | http://hdl.handle.net/10356/70615 |
| _version_ | 1826120602813988864 |
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| author | Cheow, Esther Sok Hwee |
| author2 | Sze Siu Kwan |
| author_facet | Sze Siu Kwan Cheow, Esther Sok Hwee |
| author_sort | Cheow, Esther Sok Hwee |
| collection | NTU |
| description | Atherosclerotic coronary artery disease (CAD)-related deaths will continue to rise
along with global population ageing. Although established conventional risk factors
are in place for the prediction of cardiovascular (CV) events, however, the absence
does not necessarily imply zero CAD risk. Effective screening and diagnostic
methods that stratify patient at high risk for CAD, before onset of acute events,
remain unsatisfactory, necessitating the search for novel measurable protein
biomarkers. Thankfully, biomarker discovery has taken a leap forward with the
development of mass spectrometry (MS)-based proteomics approaches, which
afforded the interrogation of the plasma proteome. The incomplete understanding in
the mechanisms in plaque destabilization and rupture, creates a knowledge gap in
the pathophysiological underlying atherosclerosis and myocardial infraction (MI). In
addition, currently there is no plasma-based screening assay that effectively
differentiates atherosclerosis from MI. The development of innovative techniques
that improves the detectable range of plasma pro teo me, is essential in advancing the
field of plasma-based biomarker discovery research. My PhD research work has
been divided into four parts (I - IV), the first three parts showcased the clinical utility
of the plasma proteome for CAD proteomics-based biomarker discovery, and in the
final part, and the successful development of a novel enrichment strategy for plasma
glycoproteins and extracellular vesicles (EV) was demonstrated. Herein, the careful
selection and systematic integration of several proteomics strategies have proven
useful in the discovery of novel plasma biomarkers of CAD, derived from (i)
undepleted plasma proteome, (ii) EV plasma proteome and (iii) carbamylated plasma
proteome. Functional linkage analyses have prompted the generation of new
hypotheses into the pathophysiological states that specifies either for atherosclerosis
or myocardial injury. The novel plasma sub-proteome enrichment technique
described here have afforded the detection of low-abundant proteins with
concentration ranging from pg/mL- ng/mL in crude plasma. In essence, this thesis
demonstrates the applicability and reliability of the different proteomics platforms in
the discovery and development of useful biomarkers that are predictive of CAD. |
| first_indexed | 2024-10-01T05:19:08Z |
| format | Thesis |
| id | ntu-10356/70615 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:19:08Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | ntu-10356/706152023-02-28T18:40:08Z Proteomics discovery of novel biomarkers for diagnosis and stratification of patient at risk for atherosclerotic cardiovascular diseases Cheow, Esther Sok Hwee Sze Siu Kwan School of Biological Sciences DRNTU::Science::Biological sciences Atherosclerotic coronary artery disease (CAD)-related deaths will continue to rise along with global population ageing. Although established conventional risk factors are in place for the prediction of cardiovascular (CV) events, however, the absence does not necessarily imply zero CAD risk. Effective screening and diagnostic methods that stratify patient at high risk for CAD, before onset of acute events, remain unsatisfactory, necessitating the search for novel measurable protein biomarkers. Thankfully, biomarker discovery has taken a leap forward with the development of mass spectrometry (MS)-based proteomics approaches, which afforded the interrogation of the plasma proteome. The incomplete understanding in the mechanisms in plaque destabilization and rupture, creates a knowledge gap in the pathophysiological underlying atherosclerosis and myocardial infraction (MI). In addition, currently there is no plasma-based screening assay that effectively differentiates atherosclerosis from MI. The development of innovative techniques that improves the detectable range of plasma pro teo me, is essential in advancing the field of plasma-based biomarker discovery research. My PhD research work has been divided into four parts (I - IV), the first three parts showcased the clinical utility of the plasma proteome for CAD proteomics-based biomarker discovery, and in the final part, and the successful development of a novel enrichment strategy for plasma glycoproteins and extracellular vesicles (EV) was demonstrated. Herein, the careful selection and systematic integration of several proteomics strategies have proven useful in the discovery of novel plasma biomarkers of CAD, derived from (i) undepleted plasma proteome, (ii) EV plasma proteome and (iii) carbamylated plasma proteome. Functional linkage analyses have prompted the generation of new hypotheses into the pathophysiological states that specifies either for atherosclerosis or myocardial injury. The novel plasma sub-proteome enrichment technique described here have afforded the detection of low-abundant proteins with concentration ranging from pg/mL- ng/mL in crude plasma. In essence, this thesis demonstrates the applicability and reliability of the different proteomics platforms in the discovery and development of useful biomarkers that are predictive of CAD. Doctor of Philosophy (SBS) 2017-05-05T06:13:38Z 2017-05-05T06:13:38Z 2017 Thesis Cheow, E. S. H. (2017). Proteomics discovery of novel biomarkers for diagnosis and stratification of patient at risk for atherosclerotic cardiovascular diseases. Doctoral thesis, Nanyang Technological University, Singapore. http://hdl.handle.net/10356/70615 10.32657/10356/70615 en 207 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Cheow, Esther Sok Hwee Proteomics discovery of novel biomarkers for diagnosis and stratification of patient at risk for atherosclerotic cardiovascular diseases |
| title | Proteomics discovery of novel biomarkers for diagnosis and stratification of patient at risk for atherosclerotic cardiovascular diseases |
| title_full | Proteomics discovery of novel biomarkers for diagnosis and stratification of patient at risk for atherosclerotic cardiovascular diseases |
| title_fullStr | Proteomics discovery of novel biomarkers for diagnosis and stratification of patient at risk for atherosclerotic cardiovascular diseases |
| title_full_unstemmed | Proteomics discovery of novel biomarkers for diagnosis and stratification of patient at risk for atherosclerotic cardiovascular diseases |
| title_short | Proteomics discovery of novel biomarkers for diagnosis and stratification of patient at risk for atherosclerotic cardiovascular diseases |
| title_sort | proteomics discovery of novel biomarkers for diagnosis and stratification of patient at risk for atherosclerotic cardiovascular diseases |
| topic | DRNTU::Science::Biological sciences |
| url | http://hdl.handle.net/10356/70615 |
| work_keys_str_mv | AT cheowesthersokhwee proteomicsdiscoveryofnovelbiomarkersfordiagnosisandstratificationofpatientatriskforatheroscleroticcardiovasculardiseases |