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  1. Article ; Online: Applications of Genome Editing Technologies in CAD Research and Therapy with a Focus on Atherosclerosis

    Michelle C. E. Mak / Rijan Gurung / Roger S. Y. Foo

    International Journal of Molecular Sciences, Vol 24, Iss 14057, p

    2023  Volume 14057

    Abstract: Cardiovascular diseases, particularly coronary artery disease (CAD), remain the leading cause of death worldwide in recent years, with myocardial infarction (MI) being the most common form of CAD. Atherosclerosis has been highlighted as one of the ... ...

    Abstract Cardiovascular diseases, particularly coronary artery disease (CAD), remain the leading cause of death worldwide in recent years, with myocardial infarction (MI) being the most common form of CAD. Atherosclerosis has been highlighted as one of the drivers of CAD, and much research has been carried out to understand and treat this disease. However, there remains much to be better understood and developed in treating this disease. Genome editing technologies have been widely used to establish models of disease as well as to treat various genetic disorders at their root. In this review, we aim to highlight the various ways genome editing technologies can be applied to establish models of atherosclerosis, as well as their therapeutic roles in both atherosclerosis and the clinical implications of CAD.
    Keywords atherosclerosis ; coronary artery disease ; genome editing ; CRISPR ; ZFN ; TALEN ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2023-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Mendelian randomization analysis of 37 clinical factors and coronary artery disease in East Asian and European populations

    Kai Wang / Xian Shi / Ziwei Zhu / Xingjie Hao / Liangkai Chen / Shanshan Cheng / Roger S. Y. Foo / Chaolong Wang

    Genome Medicine, Vol 14, Iss 1, Pp 1-

    2022  Volume 15

    Abstract: Abstract Background Coronary artery disease (CAD) remains the leading cause of mortality worldwide despite enormous efforts devoted to its prevention and treatment. While many genetic loci have been identified to associate with CAD, the intermediate ... ...

    Abstract Abstract Background Coronary artery disease (CAD) remains the leading cause of mortality worldwide despite enormous efforts devoted to its prevention and treatment. While many genetic loci have been identified to associate with CAD, the intermediate causal risk factors and etiology have not been fully understood. This study assesses the causal effects of 37 heritable clinical factors on CAD in East Asian and European populations. Methods We collected genome-wide association summary statistics of 37 clinical factors from the Biobank Japan (42,793 to 191,764 participants) and the UK Biobank (314,658 to 442,817 participants), paired with summary statistics of CAD from East Asians (29,319 cases and 183,134 controls) and Europeans (91,753 cases and 311,344 controls). These clinical factors covered 12 cardiometabolic traits, 13 hematological indices, 7 hepatological and 3 renal function indices, and 2 serum electrolyte indices. We performed univariable and multivariable Mendelian randomization (MR) analyses in East Asians and Europeans separately, followed by meta-analysis. Results Univariable MR analyses identified reliable causal evidence (P < 0.05/37) of 10 cardiometabolic traits (height, body mass index [BMI], blood pressure, glycemic and lipid traits) and 4 other clinical factors related to red blood cells (red blood cell count [RBC], hemoglobin, hematocrit) and uric acid (UA). Interestingly, while generally consistent, we identified population heterogeneity in the causal effects of BMI and UA, with higher effect sizes in East Asians than those in Europeans. After adjusting for cardiometabolic factors in multivariable MR analysis, red blood cell traits (RBC, meta-analysis odds ratio 1.07 per standard deviation increase, 95% confidence interval 1.02–1.13; hemoglobin, 1.10, 1.03–1.16; hematocrit, 1.10, 1.04–1.17) remained significant (P < 0.05), while UA showed an independent causal effect in East Asians only (1.12, 1.06–1.19, P = 3.26×10−5). Conclusions We confirmed the causal effects of 10 cardiometabolic ...
    Keywords Mendelian randomization ; Clinical factors ; Coronary artery disease ; Causal inference ; Red blood cells ; Uric acid ; Medicine ; R ; Genetics ; QH426-470
    Subject code 610
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Modified CRISPR/Cas9 mediated generation of two MKK7 knockout human embryonic stem cell lines

    C.H. Cole Sims / Matias I. Autio / Adriana Buskin / Christine Cheung / Rakesh Heer / Roger S.Y. Foo / Xin Wang

    Stem Cell Research, Vol 52, Iss , Pp 102238- (2021)

    2021  

    Abstract: Two cell lines were generated by CRISPR/Cas9 mediated knockout of MKK7 (MAP2K7) by removal of exon 1 or exons 4 through 7. These knockouts were confirmed at the transcript and protein levels. These hESCs are pluripotent and maintain tri-lineage ... ...

    Abstract Two cell lines were generated by CRISPR/Cas9 mediated knockout of MKK7 (MAP2K7) by removal of exon 1 or exons 4 through 7. These knockouts were confirmed at the transcript and protein levels. These hESCs are pluripotent and maintain tri-lineage differentiation capacity. These cell lines are a useful resource for studying MKK7 function in humans.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: A network meta-analysis of 12,116 individuals from randomized controlled trials in the treatment of depression after acute coronary syndrome

    Grace En Hui Lim / Ansel Tang / Yip Han Chin / Jie Ning Yong / Darren Tan / Phoebe Tay / Yu Yi Chan / Denzel Ming Wei Lim / Jun Wei Yeo / Kai En Chan / Kamala Devi / Colin Eng Choon Ong / Roger S. Y. Foo / Huay-Cheem Tan / Mark Y. Chan / Roger Ho / Poay Huan Loh / Nicholas W. S. Chew

    PLoS ONE, Vol 17, Iss

    2022  Volume 11

    Abstract: Background Post-acute coronary syndrome (ACS) depression is a common but not well understood complication experienced by ACS patients. Research on the effectiveness of various therapies remains limited. Hence, we sought to conduct a network meta-analysis ...

    Abstract Background Post-acute coronary syndrome (ACS) depression is a common but not well understood complication experienced by ACS patients. Research on the effectiveness of various therapies remains limited. Hence, we sought to conduct a network meta-analysis to assess the efficacy of different interventions for post-ACS depression in improving patient outcomes. Methods and findings Three electronic databases were searched for randomised controlled trials describing different depression treatment modalities in post-ACS patients. Each article was screened based on inclusion criteria and relevant data were extracted. A bivariate analysis and a network meta-analysis was performed using risk ratios (RR) and standardized mean differences (SMD) for binary and continuous outcomes, respectively. A total of 30 articles were included in our analysis. Compared to standard care, psychosocial therapy was associated with the greatest reduction in depression scores (SMD:-1.21, 95% CI: -1.81 to -0.61, p<0.001), followed by cognitive behavioural therapy (CBT) (SMD: -0.75, 95% CI: -0.99 to -0.52, p<0.001), antidepressants (SMD: -0.73, 95% CI: -1.14 to -0.31, p<0.001), and lastly, combination therapy (SMD: -0.15, 95% CI: -0.28 to -0.03, p = 0.016). No treatment modalities was found to be more effective in reducing depression scores when compared to one another. Additional analysis showed that these treatment modalities did not have significant impact on the overall mortality, cardiac mortality and recurrent myocardial infarction. Conclusion This network meta-analysis found that the treatment effect of the various psychological modalities on depression severity were similar. Future trials on psychological interventions assessing clinical outcomes and improvement in adherence to ACS-specific interventions are needed.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Differential DNA methylation correlates with differential expression of angiogenic factors in human heart failure.

    Mehregan Movassagh / Mun-Kit Choy / Martin Goddard / Martin R Bennett / Thomas A Down / Roger S-Y Foo

    PLoS ONE, Vol 5, Iss 1, p e

    2010  Volume 8564

    Abstract: Epigenetic mechanisms such as microRNA and histone modification are crucially responsible for dysregulated gene expression in heart failure. In contrast, the role of DNA methylation, another well-characterized epigenetic mark, is unknown. In order to ... ...

    Abstract Epigenetic mechanisms such as microRNA and histone modification are crucially responsible for dysregulated gene expression in heart failure. In contrast, the role of DNA methylation, another well-characterized epigenetic mark, is unknown. In order to examine whether human cardiomyopathy of different etiologies are connected by a unifying pattern of DNA methylation pattern, we undertook profiling with ischaemic and idiopathic end-stage cardiomyopathic left ventricular (LV) explants from patients who had undergone cardiac transplantation compared to normal control. We performed a preliminary analysis using methylated-DNA immunoprecipitation-chip (MeDIP-chip), validated differential methylation loci by bisulfite-(BS) PCR and high throughput sequencing, and identified 3 angiogenesis-related genetic loci that were differentially methylated. Using quantitative RT-PCR, we found that the expression of these genes differed significantly between CM hearts and normal control (p<0.01). Moreover, for each individual LV tissue, differential methylation showed a predicted correlation to differential expression of the corresponding gene. Thus, differential DNA methylation exists in human cardiomyopathy. In this series of heterogeneous cardiomyopathic LV explants, differential DNA methylation was found in at least 3 angiogenesis-related genes. While in other systems, changes in DNA methylation at specific genomic loci usually precede changes in the expression of corresponding genes, our current findings in cardiomyopathy merit further investigation to determine whether DNA methylation changes play a causative role in the progression of heart failure.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2010-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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