Background Many studies in western countries have suggested a positive association between intake of trans fatty acid (TFA) and risk of cardiovascular diseases (CVDs). In Asia, although intake of TFA was relatively low, it evidenced an increasing trend which was accompanied with an increasing prevalence of CVDs among the population. There was currently no systematic review on the relationship between intake of TFA and CVDs in Asian population. This systematic review was aimed to synthesize the association between intake of TFA and the risk of CVDs in Asian population from published literature. Methods Both English and Chinese literature published before 1st January 2014were retrieved from PubMed, Medline, Google scholaand CNKI with a combination of keywords. Studies that reported the associations between intake of TFA and CVD-related risks and those conducted among Asian population were included. The quality of eligible literature included in the review was assessed based on STROBE. Findings regarding the associations between intake of TFA and risk of CVDs were extracted and synthesized through comparing and evaluating the quality of findings across the included studies. Results Of the 378 articles retrieved from the datasets, nine studies were eligible to be included in this systematic review. The nine studies covered six Asian countries including Iran, China, Korea, Japan, Israel and India. Seven of nine studies indicated a positive association between intake of TFA and risk of CVDs while the other two reported no significant association. However, none of the included studies were interventional studies and only one was prospective cohort study. Conclusion The findings that more intake of TFA was associated with increased risk of CVDs in Asian population were consistent with that in the western population. Specific regulations to restrict the use of TFA and interventions to promote public awareness of the health effects of TFA are recommended in Asian countries. Due to limited eligible studies that covered only six Asian countries, there remains cautious to generalize the findings to other Asian countries. / published_or_final_version / Public Health / Master / Master of Public Health

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The metabolic syndrome (MS), consequent upon the pandemic of obesity and diabetes, is associated with an increased risk for cardiovascular (CV) disease. Development of sub-clinical cardiac structural and functional changes associated with CV disease risk factors may be detected on echocardiography. The extent to which these structural changes and CV risk factors are dependent on genetic factors is not clearly established. This project was designed to investigate the relationship between CV disease risk factors, cardiac structural and functional changes and underlying genetic abnormalities. Specifically, the risk factor profile and the presence of the MS were determined. This was then correlated with the echocardiographic findings and gene polymorphisms. Method: A randomly selected cohort of 1428 subjects from the Phoenix community was studied. Demographic data was collected using the WHO STEPS instrument. Blood samples for biochemistry and genetic analysis, together with anthropometric measurements, were collected. Blood pressure and echocardiography was performed on all subjects. The metabolic syndrome was classified according to the National Cholesterol Education Panel (NECP) Adult Treatment Panel III (ATP III) and International Diabetes Federation (IDF) criteria. The Lipoprotein Lipase and Human Paraoxonase-1 genes were genotyped on a Light Cycler 480 Real-Time PCR instrument, using allele-specific probes and sequencing. Results: There was a high prevalence of CV risk factors in this sample; particularly increased waist circumference (79%), obesity (64%) insulin resistance (58%) and hypertension (50%) across the age groups. This translated into a high prevalence of MS (38% using NCEP ATPIII and 46% using IDF criteria). There were significant echocardiographic differences between subjects with and without MS for chamber dimensions (p<0.001), left ventricular wall thickness (p<0.001) and mass (p<0.001), diastolic indices (E-wave {p<0.001}, trans-mitral ratio {p=0.017}) and sub-epicardial adipose tissue (SEAT) thickness (p<0.001). Stepwise multivariate analysis identified age (95% CI 0.975; 0.998), gender (95%CI 0.48; 0.9) and hypertension (95% CI 0.53; 0.99) as independent risk factors for diastolic abnormalities. Logistic regression identified age as the most significant contributor to diastolic abnormalities (OR=1.02; 95%CI 1.009; 1.03; Wald=13.4), followed by the waist circumference (OR=1.025; 95%CI 1.014; 1.037) and BMI (OR=1.075; 95% CI 1.035; 1.117). Genetic analysis showed significant associations between the heterozygous variant of Q192R genotype (PON-1 gene) and elevated HDL levels and also between this variant and obese women (p= <0.05). Conclusion: The high prevalence of CV risk factors and MS in this community has reached epidemic proportions. Although the MS was associated with significant remodelling of cardiac structure, alteration of diastolic indices and increased sub-epicardial adipose tissue thickness, BMI and waist circumference were stronger promoters of altered cardiac physiology. This augurs poorly for this population group unless intervention is introduced to address the markedly high prevalence of these culprit drivers. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2013.

University of Macau / Faculty of Science and Technology / Department of Electrical and Computer Engineering

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Long noncoding RNAs (lncRNAs) are emerging as novel regulators of macrophage biology and related inflammatory cardiovascular diseases. However, studies focused on lncRNAs in human macrophage subtypes, particularly human-specific lncRNAs that are not conserved in rodents, are limited. Through deep RNA-seq of human monocyte-derived macrophages, we identified SIMALR (suppressor of inflammatory macrophage apoptosis lincRNA), a human macrophage-specific long intergenic noncoding RNA (lincRNA), to be highly induced in the nucleus of LPS/IFNγ-stimulated macrophages. Treatment of LPS/IFNγ-stimulated THP1 human macrophages with SIMALR antisense oligonucleotides induced apoptosis of inflammatory macrophages, as shown by increased Annexin V+ macrophages, and increased protein expression of cleaved PARP, caspase 9, and caspase 3. Differential expression analysis of RNA-seq data from SIMALR knockdown versus control in human macrophages revealed Netrin 1 (NTN1), a known regulator of macrophage apoptosis, to be one of the top downregulated genes. NTN1 knockdown in LPS/IFNγ-stimulated THP1 macrophages induced apoptosis. This apoptotic phenotype was attenuated by treating LPS/IFNγ-stimulated macrophages with recombinant human NTN1 after SIMALR knockdown. Furthermore, NTN1 promoter-luciferase reporter activity was increased in HEK293T cells treated with lentiviral overexpression of SIMALR. NTN1 promoter activity is known to require HIF1α and RNA immunoprecipitation (RIP) showed that SIMALR binds HIF1α, suggesting that SIMALR may modulate HIF1α binding at the NTN1 promoter to regulate apoptosis of macrophages. In human translational studies, SIMALR was found to be upregulated in macrophages in unstable human atherosclerotic plaques, suggesting a possible mechanistic link between inflammation and cardiovascular diseases. In addition to SIMALR, through deep RNA-seq of human monocyte-derived macrophages, we identified RP11-184M15.1, a human macrophage-specific lincRNA, to be highly induced in the cytoplasm of IL-4-stimulated macrophage. Preliminary data showed that treatment of IL-4-stimulated THP1 human macrophages with RP11-184M15.1 small interfering RNA (siRNA) repressed apoptosis of resolving macrophages, as shown by decreased Annexin V+ macrophages, and reduced protein expression of cleaved PARP. Biotinylated RP11-184M15.1 pulldown coupled with mass spectrometry indicated an interaction between RP11-184M15.1 and zinc finger RNA-binding protein (ZFR). RIP corroborated the proposed interaction between RP11-184M15.1 and ZFR. RNAInter revealed mRNAs predicted to interact with ZFR, and some of those genes (e.g., ALYREF, CCNYL1) were also differentially expressed in RNA-seq data of control versus RP11-184M15.1 knockdown in IL-4-stimulated THP1 macrophages. qPCR validated that ALYREF and CCNYL1 expression are reduced with RP11-184M15.1 knockdown. In contrast, with ZFR siRNA, ALYREF and CCNYL1 mRNA expressions were elevated. Thus, a hypothesis to be further tested is that RP11-184M15.1 interacts with ZFR to regulate mRNA stability in IL-4-stimulated macrophages. Nuclear RNA export factor 1 (NXF1) was also validated by RIP to interact with RP11-184M15.1. NXF1 is a known interacting partner of ALYREF in the transcription-export (TREX) complex. With RP11-184M15.1 knockdown, the protein level of ALYREF decreased, and Ingenuity Pathway Analysis (IPA) of RNA-seq data of control versus RP11-184M15.1 knockdown revealed that THO complex subunit 5 homolog (THOC5), another component of the TREX complex, may be an upstream regulator. In addition, past studies have revealed that ALYREF and NXF1 are involved in nuclear export of inflammatory mRNAs and proinflammatory macrophage phenotype, respectively. With RP11-184M15.1 knockdown, there was decreased expression of inflammatory macrophage-associated genes. It may be possible that RP11-184M15.1 functions in mRNA export, along with NXF1 and ALYREF. In human translational studies, RP11-184M15.1 was found to be upregulated in macrophages in unstable human atherosclerotic plaques. Further work is needed to better understand the functions and molecular mechanism of RP11-184M15.1. In summary, we found that SIMALR may interact with HIF1α to regulate macrophage apoptosis via NTN1. Our preliminary work also revealed that RP11-184M15.1 may regulate apoptosis, mRNA stability and mRNA export in anti-inflammatory macrophages. Both lincRNAs may be upregulated in unstable human atherosclerotic plaques. By studying SIMALR and RP11-184M15.1, we were able to illustrate the importance of interrogating the functions of human-specific lincRNAs despite the lack of rodent models, and demonstrated roles in macrophage inflammation that may be relevant to human cardiovascular disease.