Dysregulated activation of immune-inflammatory responses contributes to vascular damage in atherosclerosis and hypertension
Bibliographic record
Abstract
Atherosclerosis and hypertension (HTN) are major contributors to the development and progression of cardiovascular disease (CVD).The underlying pathophysiology of atherosclerosis and HTN is similar in that both affect the structural and functional properties of the vasculature as a result of enhanced immune-inflammatory processes in the vascular wall.Vasoactive peptides such as angiotensin (Ang) II and endothelin (ET)-1 can contribute to vascular inflammatory responses and damage, and have been implicated in the progression of both atherosclerosis and HTN.We hypothesize that dysregulated activation of immune-inflammatory mechanisms by vasoactive peptides contributes to the progression of vascular damage in atherosclerosis and HTN.The objectives of this thesis were 1) to determine the role of ET-1mediated vascular immune-inflammatory mechanisms in progression of hyperlipidemia-induced atherosclerosis and formation of abdominal aortic aneurysms (AAA), 2) to investigate the contribution of pro-inflammatory ET-1 signaling to small artery dysfunction in hyperlipidemia-induced atherosclerosis, and 3) to study the role of anti-inflammatory T regulatory lymphocytes on vascular immune-inflammatory responses in Ang II-induced HTN.The first study shows that endothelium-specific ET-1 overexpression in atherosclerotic apolipoprotein E knockout (Apoe -/-) mice fed a high fat diet exaggerates development of aortic atherosclerotic plaques and triggers formation of AAA.This is accompanied by increase in aortic immune-inflammatory responses, spleen pro-inflammatory monocytes, and expression of matrix metalloproteinase-2 in atherosclerotic plaques.This study also suggests that the suppressive capacity of T regulatory lymphocytes may be reduced during atherosclerosis progression.The second study shows that ET-1 overexpression in high fat diet-fed atherosclerotic Apoe -/-mice results in remodeling of endothelial signaling pathways and potassium channels mediating endothelium-dependent relaxation.Although this remodeling manifests as compensatory preservation of endothelial iii function, it may in fact represent loss of regulation of endothelium-dependent relaxation in resistance arteries.The third study demonstrates that absence of T regulatory lymphocytes exaggerates microvascular damage in Ang II-induced HTN.The findings of this study show that T regulatory lymphocytes exert vascular protection in part by controlling innate and adaptive immune responses.To conclude, chronic low-grade vascular inflammation in atherosclerosis and HTN involves vasoactive peptide-mediated dysregulation of proinflammatory and anti-inflammatory mechanisms in favor of the former.Targeting immune-inflammatory mechanisms may allow us to limit the progression of atherosclerosis and HTN, and therefore the development of CVD.
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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 | 0.000 | 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".