RESUMO
In the version of this paper originally published, there was a typographical error. In the Discussion, the sentence "In line with this, Ep-CAM-deficient mice exhibited increased intestinal permeability and decreased ion transport60, which may contribute to CVD susceptibility risk59" originally read iron instead of ion transport. This error has been corrected in the HTML, PDF and print versions of the article.
RESUMO
Despite a growing body of evidence, the role of the gut microbiome in cardiovascular diseases is still unclear. Here, we present a systems-genome-wide and metagenome-wide association study on plasma concentrations of 92 cardiovascular-disease-related proteins in the population cohort LifeLines-DEEP. We identified genetic components for 73 proteins and microbial associations for 41 proteins, of which 31 were associated to both. The genetic and microbial factors identified mostly exert additive effects and collectively explain up to 76.6% of inter-individual variation (17.5% on average). Genetics contribute most to concentrations of immune-related proteins, while the gut microbiome contributes most to proteins involved in metabolism and intestinal health. We found several host-microbe interactions that impact proteins involved in epithelial function, lipid metabolism, and central nervous system function. This study provides important evidence for a joint genetic and microbial effect in cardiovascular disease and provides directions for future applications in personalized medicine.
Assuntos
Proteínas Sanguíneas/genética , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/microbiologia , Microbioma Gastrointestinal/fisiologia , Adulto , Variação Biológica Individual , Proteínas Sanguíneas/metabolismo , Encéfalo/fisiologia , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Interações entre Hospedeiro e Microrganismos/genética , Humanos , Intestinos/inervação , Intestinos/microbiologia , Metabolismo dos Lipídeos/genética , Masculino , Metagenoma/genética , Pessoa de Meia-Idade , Países Baixos , Oxirredução , Locos de Características Quantitativas/genéticaRESUMO
Targeted delivery systems recognizing specific receptors are a key element in personalized medicine. Such systems allow the delivery of therapeutics to desired sites of the body, increasing their local concentration and thus reducing the side effects. In this study, we fabricate chemically cross-linked (PAH/PAA)2 microcapsules coated with specific cell-targeting antibodies in random (via direct covalent coupling to the surface) or optimized (via supporting layer of protein A) orientation. We use these antibody-functionalized capsules to target major histocompatibility complex (MHC) class I receptors in living cells and quantify the efficiency of targeting by flow cytometry. We show for the first time the selective binding of polyelectrolyte microcapsules to MHC class I receptors, and confirm that targeting is allotype-specific. Remarkably, protein A assisted immobilization of antibodies enhances targeting efficiency by 40-50% over capsules with randomly attached antibodies. Moreover, biofunctionalized capsules reveal low levels of cytotoxicity and nonspecific binding, excluding the need of additional modification with poly(ethylene glycol). Thus, protein A coated (PAH/PAA)2 microcapsules represent a unique example of universal targeting tools providing high potential for selective binding to a broad range of cell surface receptors.
