Kinin Receptors in Vascular Biology and Pathology
Why this work is in the frame
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Bibliographic record
Abstract
Endogenous kinins are important vasoactive peptides whose effects are mediated by two G-Protein-coupled receptors (R), named B2R (constitutive) and B1R (inducible). They are involved in vascular homeostasis, ischemic pre- and post- conditioning, but also in cardiovascular diseases. They contribute to the therapeutic effects of angiotensin-1 converting enzyme inhibitors (ACEI) and angiotensin AT1 receptor blockers. Benefits derive primarily from vasodilatory, antiproliferative, antihypertrophic, antifibrotic, antithrombic and antioxidant properties, which are associated with the release of endothelial factors such as nitric oxide, prostacyclin and tissue plasminogen activator. Uncontrolled production of kinins or the inhibition of their metabolism may lead to unwanted pro-inflammatory side effects. Thus, B2R antagonism is salutary in angioedema, septic shock, stroke, and Chagas vasculopathy. B1R is virtually absent in healthy tissues, yet this receptor is induced by the cytokine pathway and the oxidative stress via the transcriptional nuclear factor NF-κB. The B1R may play a compensatory role for the lack of B2R, and its up-regulation during tissue damage may be a useful mechanism of host defense. Activation of both receptors may be beneficial, notably in neovascularisation, angiogenesis, heart ischemia and diabetic nephropathy. At the same time, B1R is a potent activator of inducible nitric oxide and NADPH oxidase, which are associated with vascular inflammation, increased permeability, insulin resistance, endothelial dysfunction and diabetic complications. The dual beneficial and deleterious effects of kinin receptors and, particularly B1R, raise an unsettled issue on the therapeutic value of B1R/B2R agonists versus antagonists in cardiovascular diseases. Hence, the Janus-face of kinin receptors needs to be seriously addressed in the upcoming clinical trials for each pathological setting.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| 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 it