Atherosclerotic Calcification: Wnt Is the Hint
Bibliographic record
Abstract
C ardiovascular diseases remain the primary cause of death. 1 Myocardial infarction (MI), angina, and stroke take >16 million lives every year, but the underlying mechanisms by which these often-fatal cardiovascular events occur tend to escape attention. 2Atherosclerosis is the underlying pathological inflammatory vascular disease not only responsible for most MIs and strokes, but it accounts for 29% of deaths worldwide. 1,3nce believed to be a passive process, it is now understood that atherosclerosis takes an active route involving several cell types, with contributions from a multitude of organ systems, molecular mechanisms, and other pathological conditions, including, but not limited to, hypertension, hyperlipidemia, and type 2 diabetes mellitus. 1,[3][4]4][5] Atherosclerosis is characterized by the accumulation of lipids, fibrous elements, and inflammatory cells within the vascular wall of medium and large muscular and elastic arteries. 1,3,6therosclerotic plaque formation leads to intimal thickening and luminal stenosis. 1Reduction of blood flow ensues, leading to ischemia of the brain, heart, and extremities and clinically manifesting as MI, angina, or stroke.The main features of atherosclerosis are endothelial dysfunction, intimal thickening, inflammation, and vascular calcification (VC). 4,7,8These processes are considered a consequence to vascular injury. 1 VC is characterized by calcium deposition in the walls of the vasculature. 5Expansion of the calcified lesion leads to thrombus formation and, if significant enough, vascular occlusion.Although the exact mechanisms for VC are unknown, there has been an increase in interest about the role Wingless (Wnt) signaling plays in disease pathogenesis.Briefly, the Wnt signaling pathway is an evolutionarily conserved pathway across kingdom Animalia and plays a crucial role in pattern formation during embryogenesis. 9The Wnt signal transduction pathway plays a crucial role in organ formation in embryonic development, cell proliferation, polarity, migration, and differentiation. 10Thus, deregulated Wnt signaling is associated with many human diseases. 11Therefore, it is justifiable to suggest that research delineating atherogenesis, with focus on the contribution of Wnt signaling in the pathogenesis of atherosclerotic calcification, is warranted. Components of the Vasculature System EndotheliumThe vascular endothelium has a multifaceted role, acting simultaneously as a permeability barrier, a nonthrombogenic surface, a regulator of vascular tone and transendothelial flow, and an inhibitor of vascular smooth muscle cell (VSMC) growth and migration. 12Under normal circumstances, endothelial cells (ECs) release an array of vasodilators and anticoagulants, such as NO and prostacyclin, which reduce platelet aggregation, monocyte and leukocyte adhesion, and VSMC proliferation. 13Under pathological conditions, ECs release factors, such as thromboxane and endothelin-1, that increase platelet aggregation, monocyte adhesion, vasoconstriction, and VSMC proliferation.Wnt signaling has been shown to be involved in EC permeability, proliferation, and survival. [14][15]5][16] Naturally, b-catenin binds to cadherins to stabilize adhesion of neighboring ECs. 17During cellular migration, however, b-catenin localizes in the nucleus, resulting in a loss of tissue integrity. 18 Vascular Smooth Muscle CellsSmooth muscle cells of the vasculature are found as 1 of 2 possible phenotypes: the first is the contractile phenotype, the predominant form of VSMC, in the tunica media; and the second is the activated synthetic phenotype, in the tunica intima. 12The differentiated contractile VSMCs can be
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.001 |
| 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".