Influences of high fat diet and ischemia on skeletal muscle pericytes
Bibliographic record
Abstract
Pericytes are mural cells on the abluminal surface of capillaries that play an essential role in capillary stabilization. They also regulate angiogenesis by guiding vessel sprouting and the maturation of newly formed sprouts. Furthermore, pericytes may have adipogenic differentiation potential. Muscle ischemia, as seen in peripheral artery disease, causes oxidative and nutrient‐deprivation stress and ultimately death of skeletal myocytes. Ischemia is a stimulus for angiogenesis, a crucial process for muscle regeneration. However, newly formed capillaries are structurally and functionally aberrant, which might be explained by dysfunction of pericytes. Recently, we showed that high‐fat (HF) diet in mice provokes a shift in skeletal muscle pericytes towards a pre‐adipocyte phenotype. This alteration may disrupt capillary remodeling processes and contribute to the worsened prognosis of PAD patients with diabetes. Thus, the purpose of this study was to assess the effects of HF diet and ischemia on skeletal muscle pericytes. We hypothesized that the number of capillary‐associated pericytes will be altered by each HF diet and ischemia and together, they may exert an additive effect. Two groups of 8 weeks old NG2/DsRed mice (that express DsRed protein under the control of the pericyte NG2 promoter) were fed normal (NC) or high fat (HF) diets (10% or 60% kcal from fat, respectively) for two weeks. The second group also underwent unilateral femoral artery ligation surgery to induce ischemia and were euthanized 14 days post‐ischemia. Analysis of EDL muscle longitudinal sections showed that HF diet decreased pericyte number/100 μm 2 vascular area (30.1 ± 0.6 (n=5) vs. 23.1 ± 2.4 (n=6) in NC and HF, respectively p<0.05). PDGFRβ+ pericytes isolated from the muscles of these mice exhibited a HF diet‐induced increase in the relative mRNA levels of leptin (0.51 ± 0.11 (n=7) vs. 0.83 ± 0.16 (n=6) in NC and HF, respectively p<0.05) and the pre‐adipocyte commitment marker Zfp423 (0.92 ± 0.11 (n=7) vs. 1.10 ± 0.14 (n=7) in NC and HF, respectively p<0.05), suggesting a shift in pericyte phenotype. Ischemic muscles of both NC and HF‐fed mice had increased numbers of capillary‐associated pericytes compared to non‐ischemic muscle (1.6 ± 0.4 and 1.4 ± 0.1fold increases in NC and HF, respectively. n=3, p<0.05). Capillary area relative to muscle area did not differ with diet or ischemia. These samples will be used to quantify pericyte proliferation and markers of pericyte phenotype in the ischemic muscles. These data provide a valuable first step in defining the behavior and functions of pericytes during muscle adaptations to the pathophysiological conditions of HF diet and ischemia.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".