The Amino Acid Homoarginine Inhibits Atherogenesis by Modulating T-Cell Function.

BACKGROUND: Amino acid metabolism is crucial for inflammatory processes during atherogenesis. The endogenous amino acid homoarginine is a robust biomarker for cardiovascular outcome and mortality with high levels being protective. However, the underlying mechanisms remain elusive. We investigated the effect of homoarginine supplementation on atherosclerotic plaque development with a particular focus on inflammation. METHODS: Female ApoE-deficient mice were supplemented with homoarginine (14 mg/L) in drinking water starting 2 weeks before and continuing throughout a 6-week period of Western-type diet feeding. Control mice received normal drinking water. Immunohistochemistry and flow cytometry were used for plaque- and immunological phenotyping. T cells were characterized using mass spectrometry-based proteomics, by functional in vitro approaches, for example, proliferation and migration/chemotaxis assays as well as by super-resolution microscopy. RESULTS: Homoarginine supplementation led to a 2-fold increase in circulating homoarginine concentrations. Homoarginine-treated mice exhibited reduced atherosclerosis in the aortic root and brachiocephalic trunk. A substantial decrease in CD3+ T cells in the atherosclerotic lesions suggested a T-cell-related effect of homoarginine supplementation, which was mainly attributed to CD4+ T cells. Macrophages, dendritic cells, and B cells were not affected. CD4+ T-cell proteomics and subsequent pathway analysis together with in vitro studies demonstrated that homoarginine profoundly modulated the spatial organization of the T-cell actin cytoskeleton and increased filopodia formation via inhibition of Myh9 (myosin heavy chain 9). Further mechanistic studies revealed an inhibition of T-cell proliferation as well as a striking impairment of the migratory capacities of T cells in response to relevant chemokines by homoarginine, all of which likely contribute to its atheroprotective effects. CONCLUSIONS: Our study unravels a novel mechanism by which the amino acid homoarginine reduces atherosclerosis, establishing that homoarginine modulates the T-cell cytoskeleton and thereby mitigates T-cell functions important during atherogenesis. These findings provide a molecular explanation for the beneficial effects of homoarginine in atherosclerotic cardiovascular disease.

Texture modified diet in German nursing homes: availability, best practices and association with nursing home characteristics.

BACKGROUND: For nursing home (NH) residents with swallowing or chewing problems, appealing texture-modified-diets (TMD) need to be available in order to support adequate nutrition. The aim of this study was to describe the availability of TMD and best practices for TMD in German NHs and to identify related NH characteristics. METHODS: Information on NH characteristics, available texture-modified (TM)-levels (soft, "minced & moist", pureed) and implemented best practices for TMD (derived from menu plan, separately visible components, re-shaped components, considering individual capabilities of the resident) was collected in a survey in German NHs. The number of TM-levels as well as the number of best practices for TMD were tested for their association with 4 structural, 16 operational and 3 resident-related NH characteristics. RESULTS: The response rate was 7.2% (n = 590) and 563 NHs were included. The vast majority of NHs (95.2%) reported offering "minced & moist" texture and 84.2% preparing separately visible meal components. Several operational characteristics were more frequently (p < 0.05) reported from NHs offering three TM-levels (27.7%) or four best practices for TMD (13.0%) compared to NHs offering one TM-level (28.4%) or one best practice for TMD (20.1%): special diets and delivery forms (e.g. fingerfood 71.2% vs 38.8%; 80.8% vs. 44.3%), written recipes (69.9% vs. 53.1%; 68.5% vs. 53.9%), a dietetic counseling service (85.9% vs. 66.3%; 89.0% vs. 65.2%), a quality circle for nutritional care (66.7% vs. 43.8%; 71.2% vs. 50.4%), regular staff training (89.7% vs. 73.1%; 95.9% vs. 74.8%) and process instructions (73.7% vs. 53.1%; 75.3% vs. 47.8%). No associations were found regarding structural and resident-related NH characteristics, except a higher percentage of residents receiving TMD in NHs with three compared to one TM-level (median 16.3% vs. 13.2%, p = 0.037). CONCLUSION: All participating NHs offer some form of TMD, but only a small number offers a selection of TMD and pays adequate attention to its preparation. Operational NH characteristics - which might reflect a general nutritional awareness of the NH - seem to be pivotal for provision of TMD, whereas neither structural nor resident-related characteristics seem to play a role in this regard.