Abstract 13173: Loss of ACE2 in a Diabetic Obese Setting Exacerbates Cardiovascular Dysfunction in the Setting of Gut Dysbiosis
Bibliographic record
Abstract
Introduction: COVID-19 disproportionately affects older, male obese patients leading to a high prevalence of adverse outcomes. SARS-CoV-2 mediated ACE2 loss may further increase the susceptibility of these patients to adverse outcomes. Loss of ACE2 may be a causative factor in cardiovascular (CV) injury independent of primary viral-mediated injury. Methods: Male, 6-month-old, diabetic, obese db/db Ace2 -/y (double mutant, DM) mice and respective WT, Ace2 -/y , and db/db controls (n=12) were assessed for injury across the gut-heart axis. Cardiovascular parameters were evaluated by echocardiography, pressure-volume loops, and histology. Alterations in gut permeability were determined by measuring plasma peptidoglycan (PGN) levels and immunological staining of microvilli structure. Metagenomics and metatranscriptomics determined the functional and phyla alterations of the gut microbiota. Results: Loss of ACE2 in diabetic obese mice led to increased left atrium diameter (P<0.001) and elevated left ventricular end-diastolic pressures (P<0.05) compared to db/db mice. Cardiac remodeling was prevalent in DM hearts with increased cardiomyocyte hypertrophy (P<0.001), cardiac fibrosis (P<0.05), lipid accumulation (P<0.01), and reactive oxygen species (ROS; P<0.01) compared to db/db mice. This was associated with elevated aortic ROS (P<0.001), and impaired femoral artery vasodilation (P<0.001). DM mice had increased gut-blood barrier permeability, with elevated plasmalemma vesicle-associated protein-1 staining (P<0.05) and plasma PGN levels (P<0.01). Principal coordinates analysis of gut microbial β diversity showed distinct populations across the experimental groups (P<0.05). Loss of ACE2 in db/db mice resulted in the divergence of metatranscriptomics profiles with increased expression of neutral amino acid metabolism, PGN and toxin production pathways. Conclusions: Loss of ACE2 in diabetic obese mice worsened cardiovascular dysfunction and adverse remodeling and was associated with an altered gut-cardiovascular axis characterized by elevated gut permeability and dysbiosis. Our results support worsening CV injury arising from the loss of ACE2 and may indicate a pathway of SARS-CoV-2 infection mediated CV injury.
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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) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".