Metabolic syndrome and heart failure with preserved ejection fraction: a new model of pulmonary hypertension associated with left heart disease
Bibliographic record
Abstract
Rationale Heart failure (HF) with preserved ejection fraction (HFpEF) is the more common cause of HF and affecting over 50% of all patients with HF. Interestingly 50% of HFpEF culminates to pulmonary hypertension (PH), which confers poor prognosis. On the other hand, metabolic syndrome (MS), which affects more than 34% of adults in the world, is strongly associated with PH (pulmonary venous hypertension (94.1%); pulmonary arterial hypertension (34.3%)) and HFpEF (prevalence of 35%). Taken together, these results suggest that MS and HFpEF, which are two major healthcare challenges in the occidental society, may predispose to PH. Unfortunately; studies supporting this hypothesis remain limited by the lack of good pre‐clinical models that preclude extensive investigation. We developed a new animal model for WHO2 pulmonary hypertension associating HFpEF and metabolic syndrome. Methods/Results Using supra‐coronary aortic banding, we first induced HFpEF in wistar male rats characterized by left ventricular (LV) hypertrophy, raise in LV systolic pressure, LV end‐diastolic pressure and no significant modification of LV end‐diastolic area and LV ejection fraction, 5 weeks post‐surgery (n=5; p<0,05). We then induced MS with high fat diet and daily injection of olanzapine (4mg/kg for 21 days) initiated two weeks after surgery. Establishment of MS was confirmed by significant increase in the fat/lean body mass (minispec Brucker lf90) and insulin resistance (high blood insulin level) compared to vehicle‐treated rats (n=5 per group; P <0.05). As expected, compared to healthy and sham surgery, HFpEF rats (n=5) displayed PH characterized by a significant decreased pulmonary acceleration time and tricuspid annular plane excursion (PAAT; TAPSE; echocardiography; P <0.05) and increased mean pulmonary arterial pressure and right ventricular systolic pressure (PAP, RVSP; P <0.05) (right heart catheterizations in closed chest). Interestingly, MS‐HFpEF displayed significant worsening in hemodynamic parameters (PAAT, TAPSE, PAP, RVSP) compared to HFpEF rats without MS ( P< 0.05, n=5 per group). Interestingly, remodelling of the distal pulmonary arteries, strongly correlates with fat/lean body mass and was significantly increased in MS‐HFpEF rats compared to the other conditions (p<0.05, n=5 per group). Conclusion In the present study we demonstrated that metabolic syndrome worsens PH associated with HFpEF. Therefore, the MS and HFpEF combination represents a novel and attractive animal model to study WHO2 PH.
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 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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".