Biomedical subjects

Yang Liu

Publications and source records attributed to Yang Liu.

At least 55 records · Page 3Linked to original sources

PubMed2025

Gain-of-function PPM1D mutations attenuate ischemic stroke.

Identification of genetic aberrations in stroke, the second leading cause of death worldwide, is of paramount importance for understanding the disease pathogenesis and generating new therapies. Whole-genome sequencing from 10,241 ischemic stroke patients identified eight patients carrying gain-of-function mutations on coding variants in the protein phosphatase magnesium-dependent 1 δ (PPM1D) gene. Patients carrying PPM1D mutations exhibit better stroke-related clinical phenotypes, including improvements in peripheral inflammation, fibrinogen, low-density lipoprotein, cholesterol and plateletcrit level. Experimental brain ischemia in Ppm1d-deficient (Ppm1d-/-) mice resulted in enlarged lesions and pronounced neurological impairments. Spatial transcriptomics revealed a distinct Ppm1d-associated gene expression pattern, indicating disrupted endothelial homeostasis during ischemic brain injury. Proteomic analysis demonstrated that differentially expressed proteins in primary brain endothelial cells from Ppm1d-/- mice were significantly enriched in the peroxisome proliferator-activated receptors (PPARs)-mediated metabolic signaling. Mechanistically, Ppm1d deficiency promoted aberrant fatty acid β-oxidation and increased oxidative stress, which impaired endothelial cell function through the PPARα pathway. A small molecule, T2755, was identified to engage Trp427 and stabilize PPM1D, thereby mitigating ischemic brain injury in mice. Collectively, we find that PPM1D protects against ischemic brain injury and validates its pharmacological stabilizer T2755 as a promising therapy for ischemic stroke. Gain-of-function PPM1D mutations attenuate ischemic cerebral injury. Whole-genome sequencing data of 10,241 ischemic stroke patients from the Third Chinese National Stroke Registry (CNSR-III) identified eight patients with gain-of-function mutations in the protein phosphatase magnesium-dependent 1 δ (PPM1D) gene (17q23.2). These mutation carriers displayed improved peripheral inflammation, decreased fibrinogen, low-density lipoprotein, cholesterol and plateletcrit level. Ppm1d-deficient (Ppm1d-/-) mice exhibited exacerbated stroke outcomes, characterized by enlarged infarct volumes, disrupted cerebrovascular architecture, and enhanced neuro-inflammation. Mechanistically, Ppm1d deficiency induced the disturbance of endothelial fatty acid metabolism involving the PPARα pathway. Through integrated computational modeling, virtual screening, and in vitro validation, T2755 was identified as a small molecule PPM1D stabilizer. Pharmacological PPM1D stabilization with T2755 significantly attenuated ischemic brain injury in murine models.

Aged↗

PubMed2025

Multiple features of cell-free mtDNA for predicting transarterial chemoembolization response in hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) is the primary treatment modality for advanced HCC, yet its efficacy assessment and prognosis prediction largely depend on imaging and serological markers that possess inherent limitations in terms of real-time capability, sensitivity, and specificity. Here, we explored whether multiple features of cell-free mitochondrial DNA (cf-mtDNA), including copy number, mutations, and fragmentomics, could be used to predict the response and prognosis of patients with HCC undergoing TACE treatment. METHODS: A total of 60 plasma cell-free DNA samples were collected from 30 patients with HCC before and after the first TACE treatment and then subjected to capture-based mtDNA sequencing and whole-genome sequencing. RESULTS: Comprehensive analyses revealed a clear association between cf-mtDNA multiple features and tumor characteristics. Based on cf-mtDNA multiple features, we also developed HCC death and progression risk prediction models. Kaplan-Meier curve analyses revealed that the high-death risk or high-progression-risk group had significantly shorter median overall survival (OS) and progression-free survival than the low-death risk or low-progression-risk group (all p<0.05). Moreover, the change in cf-mtDNA multiple features before and after TACE treatment exhibited an exceptional ability to predict the risk of death and progression in patients with HCC (log-rank test, all p<0.01; HRs: 0.36 and 0.33, respectively). Furthermore, we observed the consistency of change between the cf-mtDNA multiple features and copy number variant burden before and after TACE treatment in 40.00% (12/30) patients with HCC. CONCLUSIONS: Altogether, we developed a novel strategy based on profiling of cf-mtDNA multiple features for prognosis prediction and efficacy evaluation in patients with HCC undergoing TACE treatment.

Humans↗

PubMed2025

Comprehensive discovery and functional characterization of the noncanonical proteome.

The systematic identification and functional characterization of noncanonical translation products, such as novel peptides, will facilitate the understanding of the human genome and provide new insights into cell biology. Here, we constructed a high-coverage peptide sequencing reference library with 11,668,944 open reading frames and employed an ultrafiltration tandem mass spectrometry assay to identify novel peptides. Through these methods, we discovered 8945 previously unannotated peptides from normal gastric tissues, gastric cancer tissues and cell lines, nearly half of which were derived from noncoding RNAs. Moreover, our CRISPR screening revealed that 1161 peptides are involved in tumor cell proliferation. The presence and physiological function of a subset of these peptides, selected based on screening scores, amino acid length, and various indicators, were verified through Flag-knockin and multiple other methods. To further characterize the potential regulatory mechanisms involved, we constructed a framework based on artificial intelligence structure prediction and peptide‒protein interaction network analysis for the top 100 candidates and revealed that these cancer-related peptides have diverse subcellular locations and participate in organelle-specific processes. Further investigation verified the interacting partners of pep1-nc-OLMALINC, pep5-nc-TRHDE-AS1, pep-nc-ZNF436-AS1 and pep2-nc-AC027045.3, and the functions of these peptides in mitochondrial complex assembly, energy metabolism, and cholesterol metabolism, respectively. We showed that pep5-nc-TRHDE-AS1 and pep2-nc-AC027045.3 had substantial impacts on tumor growth in xenograft models. Furthermore, the dysregulation of these four peptides is closely correlated with clinical prognosis. Taken together, our study provides a comprehensive characterization of the noncanonical proteome, and highlights critical roles of these previously unannotated peptides in cancer biology.

Humans↗

PubMed2025

Broad-spectrum antibacterial and antibiofilm activity of dandelion endophytic bacteria against multidrug-resistant bacteria.

Microbial secondary metabolites have long served as a key source of natural product-based drugs. This study evaluates the antibacterial, antibiofilm, and antioxidant activities of endophytic bacteria derived from dandelion, focusing on their effects against multidrug-resistant (MDR) clinical isolates. In total, 33 endophytic bacteria strains were isolated from Taraxacum ohwianum, representing 15 genera. Among these, 13 exhibited antibacterial activity, with 6 demonstrating efficacy against MDR clinical isolates. The endogenous strain Bacillus velezensis DR8 showed strong antibacterial activity against all three MDR strains tested and exerted inhibitory effects on the biofilm formation and dispersal of methicillin-resistant Staphylococcus aureus. Genome sequencing and antibiotics and secondary metabolite analysis shell analysis revealed that this strain harbors 12 biosynthetic gene clusters (BGCs) associated with secondary metabolite production. Of these, seven BGCs exhibited ≥ 80% similarity to known clusters, suggesting the potential to synthesize surfactin, difficidin, fengycin, bacillaene, macrolactin H, bacilysin, and bacillibactin. Overall, these findings indicate that endophytic bacteria from dandelion are a potential source of antibacterial compounds and biofilm formation inhibitors.

Endophytes↗

PubMed2025

Donor MHC-specific thymus vaccination allows for immunocompatible allotransplantation.

Organ transplantation is the last-resort option to treat organ failure. However, less than 10% of patients benefit from this only option due to lack of major histocompatibility complex (MHC)-matched donor organs and 25%-80% of donated organs could not find MHC-matched recipients. T cell allorecognition is the principal mechanism for allogeneic graft rejection. We herein present a "donor MHC-specific thymus vaccination" (DMTV) strategy to induce T cell tolerance to both autologous and allogeneic donor MHC. Allogeneic MHC molecules were expressed in the recipient thymus through adeno-associated virus-mediated delivery, which led to stable expression of allogeneic MHC together with the autologous MHC in the engineered thymus. During local T cell education, those T cells recognizing either autologous MHC or allogeneic MHC were equally depleted. We constructed C57BL/6-MHC and BALB/c-MHC dual immunocompatible mice via thymus vaccination of C57BL/6-MHC into the BALB/c thymus and observed long-term graft tolerance after transplantation of C57BL/6 skin and C57BL/6 mouse embryonic stem cells into the vaccinated BALB/c mice. We also validated our DMTV strategy in a bone marrow, liver, thymus (BLT)-humanized mouse model for immunocompatible allotransplantation of human embryonic stem cells. Our study suggests that the DMTV strategy is a potent avenue to introduce a donor compatible immune system in recipients, which overcomes the clinical dilemma of the extreme shortage of MHC-matched donor organs for treating patients with end-stage organ failure.

Animals↗

PubMed2025

Antiviral Activity of the MEK1/2 Inhibitor Trametinib Against Lymphocytic Choriomeningitis Virus.

The lymphocytic choriomeningitis virus (LCMV) is a widespread pathogen that causes mild-to-severe infections to severe outcomes. In this study, we explored the potential of trametinib, a mitogen-activated protein kinase (MAPK) inhibitor, as an antiviral agent against LCMV. Trametinib demonstrated significant antiviral activity against two distinct LCMV strains, Armstrong and Cl13, with promising half-maximal inhibitory concentrations (IC50) and selectivity indices (SI) indicating its potency and safety profile. Mechanistic investigations revealed that trametinib interfered with multiple stages of the LCMV life cycle, including membrane fusion and genomic replication, leading to the robust inhibition of viral proliferation. Furthermore, trametinib disrupted the MEK/ERK signaling pathway, which is crucial for LCMV infection. In both in vitro and in vivo experiments, trametinib effectively reduced viral loads and mitigated pathological damage to the spleen and liver tissues. Overall, our findings suggest that trametinib is a promising novel therapeutic option for combating LCMV infection by targeting key stages of the viral life cycle and disrupting host cellular signaling pathways. Further exploration of the antiviral properties of trametinib is likely to pave the way for its clinical development as a treatment for LCMV infections.

Pyridones↗

PubMed2025

Bergamottin, A Natural Bioactive Compound, Inhibits Dabie Bandavirus Infection In Vitro and In Vivo.

Severe fever with thrombocytopenia syndrome (SFTS) is a novel, highly fatal disease caused by Dabie bandavirus (DBV), also referred to as severe fever with thrombocytopenia syndrome virus (SFTSV). DBV is endemic to many Asian countries, and its incidence has recently increased. However, there are currently no specific therapies for combating DBV infection. Here we verified whether the natural bioactive compound, bergamottin, effectively inhibits DBV in vitro and in vivo. A primary in vitro study suggested that bergamottin suppressed DBV infection both in Vero E6 and Huh-7 cells in a dose-dependent manner. Time-of-addition assay revealed that bergamottin interferes with DBV infection at multiple stages of the viral life cycle. Moreover, bergamottin inhibits viral internalization and effectively reduces viral genome replication. The efficacy of bergamottin at doses of 75 and 120 mg/kg/d against DBV infection in an IFNAR-/- mouse infection model was investigated. Oral delivery at a dose of 120 mg/kg/d significantly reduced the number of the viral RNA copies in the kidneys, spleen, and lungs. These findings highlight that bergamottin is a promising agent that could be further developed as a therapeutic agent against DBV infection.

Animals↗

PubMed2025

Conservation genomics of a threatened subtropical Rhododendron species highlights the distinct conservation actions required in marginal and admixed populations.

With the impact of climate change and anthropogenic activities, the underlying threats facing populations with different evolutionary histories and distributions, and the associated conservation strategies necessary to ensure their survival, may vary within a species. This is particularly true for marginal populations and/or those showing admixture. Here, we re-sequence genomes of 102 individuals from 21 locations for Rhododendron vialii, a threatened species distributed in the subtropical forests of southwestern China that has suffered from habitat fragmentation due to deforestation. Population structure results revealed that R. vialii can be divided into five genetic lineages using neutral single-nucleotide polymorphisms (SNPs), whereas selected SNPs divide the species into six lineages. This is due to the Guigu (GG) population, which is identified as admixed using neutral SNPs, but is assigned to a distinct genetic cluster using non-neutral loci. R. vialii has experienced multiple genetic bottlenecks, and different demographic histories have been suggested among populations. Ecological niche modeling combined with genomic offset analysis suggests that the marginal population (Northeast, NE) harboring the highest genetic diversity is likely to have the highest risk of maladaptation in the future. The marginal population therefore needs urgent ex situ conservation in areas where the influence of future climate change is predicted to be well buffered. Alternatively, the GG population may have the potential for local adaptation, and will need in situ conservation. The Puer population, which carries the heaviest genetic load, needs genetic rescue. Our findings highlight how population genomics, genomic offset analysis, and ecological niche modeling can be integrated to inform targeted conservation.

Rhododendron↗

PubMed2024

Gut microbial genomes with paired isolates from China illustrate probiotic and cardiometabolic effects.

The gut microbiome displays genetic differences among populations, and characterization of the genomic landscape of the gut microbiome in China remains limited. Here, we present the Chinese Gut Microbial Reference (CGMR) set, comprising 101,060 high-quality metagenomic assembled genomes (MAGs) of 3,707 nonredundant species from 3,234 fecal samples across primarily rural Chinese locations, 1,376 live isolates mainly from lactic acid bacteria, and 987 novel species relative to worldwide databases. We observed region-specific coexisting MAGs and MAGs with probiotic and cardiometabolic functionalities. Preliminary mouse experiments suggest a probiotic effect of two Faecalibacillus intestinalis isolates in alleviating constipation, cardiometabolic influences of three Bacteroides fragilis_A isolates in obesity, and isolates from the genera Parabacteroides and Lactobacillus in host lipid metabolism. Our study expands the current microbial genomes with paired isolates and demonstrates potential host effects, contributing to the mechanistic understanding of host-microbe interactions.

Probiotics↗

PubMed2007

Single nucleotide polymorphisms in the proximal promoter region of apolipoprotein M gene (apoM) confer the susceptibility to development of type 2 diabetes in Han Chinese.

OBJECTIVE: Dyslipidemia correlating to insulin resistance is one of the key features in type 2 diabetes (T2D). Recent studies have demonstrated that apolipoprotein M (apoM) is important for the formation of prebeta-high-density lipoprotein (HDL) and cholesterol (CHO) efflux in macrophages to HDL. In the present study, we investigated the potential association of apoM genetic variation with the development of T2D. METHODS: Single nucleotide polymorphisms (SNPs) C-1065A, T-855C and T-778C in the proximal promoter region of apoM gene were validated to represent in Han Chinese. Further genotyping experiments in 170 T2D patients and 156 non-diabetic control subjects were performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Single marker analysis for SNP T-778C indicated that T2D patients had increased frequency of C allele in comparison with non-diabetic controls (10.6% versus 5.8%, P = 0.026, OR = 1.934). In non-diabetic controls, the carriers with CT and CC genotypes had higher plasma CHO (221.7 versus 204.2 mg/dL, P = 0.033) and fasting plasma glucose (FPG) (92.6 versus 89.7 mg/dL, P = 0.041) levels than the subjects with TT genotype. Further analysis with adjustment for age, BMI, SBP, DBP, CHO and TG demonstrated that this SNP was strongly associated with T2D (P = 0.013, OR = 2.287). Haplotype analysis for those three SNPs, however, indicated that the common haplotypes were less informative than studying the role of the T-778C variant independently of the haplotype context. CONCLUSION: The present study provided the first evidence that SNP T-778C in the proximal promoter region of apoM gene was associated with the levels of plasma CHO and FPG and also conferred the risk in the development of T2D among Han Chinese.

Aged↗

PubMed2007

Tip cooling effect and failure mechanism of field-emitting carbon nanotubes.

The cooling effect accompanying field electron emission has been considered for a single carbon nanotube (CNT) used as a field emission (FE) electron source. An improved model for the failure mechanism of field emitting CNTs has been proposed and validated. Our model predicts a maximum temperature (T-max) located at an interior point rather than the tip of the CNTs, and the failure of the CNT emitters tends to take place at the T-max point, inducing a segment by segment breakdown process. A combination of Joule heating and electrostatic force effect is proposed responsible for initiating the failure of the field emitting CNT and validated by in situ FE observation.

Equipment Failure↗

PubMed2007

Computational approaches to phenotyping: high-throughput phenomics.

The recent completion of the Human Genome Project has made possible a high-throughput "systems approach" for accelerating the elucidation of molecular underpinnings of human diseases, and subsequent derivation of molecular-based strategies to more effectively prevent, diagnose, and treat these diseases. Although altered phenotypes are among the most reliable manifestations of altered gene functions, research using systematic analysis of phenotype relationships to study human biology is still in its infancy. This article focuses on the emerging field of high-throughput phenotyping (HTP) phenomics research, which aims to capitalize on novel high-throughput computation and informatics technology developments to derive genomewide molecular networks of genotype-phenotype associations, or "phenomic associations." The HTP phenomics research field faces the challenge of technological research and development to generate novel tools in computation and informatics that will allow researchers to amass, access, integrate, organize, and manage phenotypic databases across species and enable genomewide analysis to associate phenotypic information with genomic data at different scales of biology. Key state-of-the-art technological advancements critical for HTP phenomics research are covered in this review. In particular, we highlight the power of computational approaches to conduct large-scale phenomics studies.

Computational Biology↗

PubMed2006

Surfactant-assistant and facile synthesis of hollow ZnS nanospheres.

Small and monodisperse ZnS hollow nanospheres with outer diameter ranging from 60 to 70 nm and wall thickness of 15-20 nm were fabricated in a large scale by a simple surfactant polyethylene glycol (PEG) assisted method. The diameter and the wall thickness of the hollow nanospheres could be controlled by manipulating the amount of PEG and the aging time, respectively. Moreover, the wall of these hollow nanospheres is very compact. The product was characterized by X-ray power diffraction (XRD), transmission electron microscopy (TEM), UV-vis spectrum and fluorescence spectroscopy. The photocatalytic activity of as-prepared ZnS hollow nanospheres was also evaluated by using methyl orange (MO) as a model organic compound and the result revealed that their photocatalytic activity is a little lower than that of Degussa P25 TiO(2) but better than that of ZnS nanocrystals prepared by literature method. Furthermore, a rational mechanism to the formation and evolution of the products is proposed.

Nanotubes↗

PubMed2006

Suppression of microglial inflammatory activity by myelin phagocytosis: role of p47-PHOX-mediated generation of reactive oxygen species.

Multiple sclerosis (MS) is pathologically characterized by inflammatory demyelination and neuronal injury. Although phagocytosis of myelin debris by microglia and macrophages in acute MS lesions is well documented, its pathophysiological significance is unclear. Using real-time quantitative PCR, flow cytometry, ELISA, and reactive oxygen species (ROS) measurement assays, we demonstrated that phagocytosis of myelin modulates activation of microglial cells prestimulated by interferon-gamma (IFN-gamma) or a combination of IFN-gamma and lipopolysaccharide with a biphasic temporal pattern, i.e., enhanced production of proinflammatory mediators during the first phase (< or = 6 h), followed by suppression during the second (6-24 h) phase. In this second phase, myelin phagocytosis leads to an enhanced release of prostaglandin E2 and ROS in microglia, whereas the production of anti-inflammatory cytokines (particularly interleukin-10) remains unchanged. Suppression of inflammatory microglial activation by myelin phagocytosis was reversed by treatment with superoxide dismutase and catalase, by inhibition of the NADPH-oxidase complex, or by specific knockdown of the NADPH-oxidase-required adaptor p47-phagocyte oxidase (PHOX). Furthermore, we observed that myelin phagocytosis destabilized tumor necrosis factor-alpha and interferon-induced protein-10 mRNA through an adenine-uridine-rich elements-involved mechanism, which was reversed by blocking the function of NADPH-oxidase complex. We conclude that phagocytosis of myelin suppresses microglial inflammatory activities via enhancement of p47-PHOX-mediated ROS generation. These results suggest that intervention in ROS generation could represent a novel therapeutic strategy to reduce neuroinflammation in MS.

Animals↗

PubMed2006

Influence of calcium phosphate crystal assemblies on the proliferation and osteogenic gene expression of rat bone marrow stromal cells.

Calcium phosphates (CaPs) have been investigated as substrates to promote bone formation both in vitro and in vivo. The aim of this study was to examine the proliferation and differentiation of rat bone marrow stromal cells (BMSCs) cultured on three-dimensional (3D) octacalcium phosphate (OCP) crystal assemblies. The cytotoxicity of OCP crystal assemblies was evaluated by measuring the lactate dehydrogenase (LDH) release from BMSCs during 10h of incubation with OCP crystal assemblies. The proliferation of BMSCs on OCP crystal assemblies in medium with or without osteogenic supplements was also investigated using the MTT assay with tissue culture treated plastic (TP) as the control. The tissues formed by BMSCs cultured on OCP crystal assemblies for 24 days were examined following staining with haematoxylin and eosin (H&E), alkaline phosphatase (ALP) and Van Gieson's techniques. The influence of OCP crystal assemblies on mRNA expression of alpha chain of collagen type I (Coll-Ia), ALP and osteocalcin (OC), osteonectin (ON), osteopontin (OP), lumican, Cbfa1, EST317 and EST350 by the BMSCs were also investigated using semi-quantitative RT-PCR. Although OCP crystals were relatively cytotoxic compared with TP, proliferation of BMSCs occurred when seeded onto OCP crystal assemblies. BMSCs cultured on OCP demonstrated similar proliferation rates as found on the control and no significant difference (P<0.05) in the number of cells cultured in medium supplemented with or without osteogenic additives on TP and OCP. The deposition of collagen and ALP were detected in tissue synthesised by BMSCs cultured on OCP crystals assemblies. OCP crystal assemblies down-regulated basal bone ECM proteins, including Coll-Ia, ON and lumican, in the first week of culture, whilst up-regulation of the same genes was observed after 24 days of culture. The observed down-regulation of Cbfa1 on OCP substrates was consistent with the negative effect of OCP crystal assemblies on the genes encoding bone ECM proteins. The up-regulation of OC mRNA expression by OCP crystal assemblies could be related to the requirement for synthesis of more OC proteins to control the concentration of calcium ions in culture medium.

Animals↗

PubMed2006

A cancer-associated PCNA expressed in breast cancer has implications as a potential biomarker.

Two isoforms of proliferating cell nuclear antigen (PCNA) have been observed in breast cancer cells. Commercially available antibodies to PCNA recognize both isoforms and, therefore, cannot differentiate between the PCNA isoforms in malignant and nonmalignant breast epithelial cells and tissues. We have developed a unique antibody that specifically detects a PCNA isoform (caPCNA) associated with breast cancer epithelial cells grown in culture and breast-tumor tissues. Immunostaining studies using this antibody suggest that the caPCNA isoform may be useful as a marker of breast cancer and that the caPCNA-specific antibody could potentially serve as a highly effective detector of malignancy. We also report here that the caPCNA isoform functions in breast cancer-cell DNA replication and interacts with DNA polymerase delta. Our studies indicate that the caPCNA isoform may be a previously uncharacterized detector of breast cancer.

Antibodies↗

PubMed2006

Pluripotency and chimera competence of an embryonic stem cell line from the sea perch (Lateolabrax japonicus).

A stable GFP-expressing (GFP(+)LJES1) cell strain was developed from the LJES1 cells obtained from sea perch (Lateolabrax japonicus,) embryos. GFP(+)LJES1 cells were induced in vitro by RA to differentiate into a variety of cell types and also had the ability to form embryoid body-like structures in suspension culture. To determine the differentiation potential of LJES1 cells in vivo, GFP(+)LJES1 cells were transplanted into sea perch and zebrafish embryos at mid-blastula stage. Twenty out of 478 transplanted sea perch embryos contained GFP-expressing LJES1 cells 24 h after microinjection. Fifteen chimera embryos developed into fry. In these chimeras, the GFP(+)LJES1 cells contributed to a variety of tissues including the head and trunk. In zebrafish, 221 embryos were microinjected with GFP(+)LJES1 cells and 22 chimera embryos and fries expressing GFP were obtained. Donor GFP(+)LJES1 cells contributed to various tissues in head and trunk of zebrafish embryos and hatched fry.

Animals↗

PubMed2006

Moderately elevated plant sterol levels are associated with reduced cardiovascular risk--the LASA study.

Functional foods with supplementation of plant sterols are already used by millions of people. However, at the same time it is current scientific thinking that elevation of plant sterols in the circulation causes coronary heart disease. Therefore, this study aimed to define the risk for coronary heart disease associated with moderately high plant sterol plasma levels in a cohort of elderly. In this study, we evaluated the association between plant sterols and coronary heart disease in a cohort of 1242 subjects older than 65 years, participating at the Longitudinal Aging Study Amsterdam (LASA). Concentrations of sitosterol, campesterol, brassicasterol and stigmasterol were assessed using highly sensitive and specific gas chromatography-mass spectrometry-selected ion-monitoring. Plant sterol concentrations (and their ratios to cholesterol) were slightly, however, significantly lower in patients with coronary heart disease. Moreover, high plasma concentrations of a marker plant sterol, sitosterol, were associated with a markedly reduced risk for coronary heart disease (OR 0.78, CI 0.62-0.98, p<0.05). In contrast neither plant stanols (sitostanol or campestanol) nor the cholesterol synthesis markers (lathosterol, lanosterol and desmosterol) nor their ratios to cholesterol were significantly different in the study groups. These data suggest that plant sterols could have neutral or even protective effects on development of coronary heart disease, which have to be confirmed in interventional trials.

Aged↗