Vascular regenerative cell content in people with elevated lipoprotein(a): primary results of the Lp(a)-VRCE study
Bibliographic record
Abstract
Abstract Background Elevated levels of lipoprotein(a) [Lp(a)] is an independent and causal genetic risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). Vascular regenerative (VR) cell exhaustion, or the depletion of circulating progenitor cells that mediate blood vessel repair, represents a novel indicator of compromised vessel repair in people living with type 2 diabetes or obesity, and among South Asian adults with elevated CVD risk. We hypothesize that Lp(a) levels may correlate positively with VR cell depletion. Purpose The cross-sectional, observational, multi-site Lp(a)-VRCE study compared the frequencies of circulating VR cell subsets from a total of 40 individuals with Lp(a) ≥100 nmol/L [High Lp(a); n=20] and Lp(a) <100 nmol/L [Low Lp(a); n=20]. Methods Peripheral blood mononuclear cells were subject to multi-parameter flow cytometry analyses based on the activity of high aldehyde dehydrogenase (ALDH), an antioxidative enzyme that is conserved in progenitor cells, in combination with side scatter and lineage-specific cell surface markers. Results Key baseline characteristics were comparable between the study groups and are summarized in the Table. Mean (SD) Lp(a) levels for the High and Low Lp(a) subgroups were 249.9±90.8 and 28.4±18.2 nmol/L (p<0.001) respectively. Approximately one-third of the participants was female; mean age of the cohort was 59 years; mean total cholesterol and eGFR were lower, and creatinine higher in the High Lp(a) group. While most in the High Lp(a) group were on a statin (90%), only 60% of the low Lp(a) participants were taking a statin. Individuals in the High Lp(a) group had lower frequencies of ALDHhiSSClowCD133+ (43±6 vs 51±8%, p<0.001) and ALDHhiSSClowCD34+CD133+ (44±7 vs 53±11%, p<0.01) early myeloid progenitor cells with previously established vessel regenerative functions. Those in the High Lp(a) group also exhibited increased M1-like pro-inflammatory polarization among circulating monocytes (ALDHhiSSCmidCD86+CD163-, 6.5±2.8 vs 4.0±2.6%, p<0.01). Conclusion Lp(a)-VRCE provides the first translational evidence that Lp(a) levels ≥100 nmol/L are associated with reduced VR myeloid progenitor cell content that is responsible for vessel repair, and increased M1-polarized monocyte content that contributes to plaque inflammation. Recovery of vessel repair via Lp(a)-lowering strategies may represent a novel approach to decrease vascular risk.Table Figure
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".