Differential angiogenic response contributes to sexual dimorphism in right ventricular adaptation in male and female Fischer CDF rats subjected to pulmonary artery banding model
Notice bibliographique
Résumé
Background: Female sex has been associated with better right ventricular (RV) adaptation and survival in patients with elevated RV afterload; however, the mechanisms underlying these differences remain unclear. Therefore, we studied the mechanisms underlying sex differences in RV remodeling and development of RHF using the rat pulmonary artery banding (PAB) model. Methods: Adult male and female Fischer CDF rats were subjected to PAB or sham surgery and echocardiography was performed at 1- or 2-weeks post-PAB to evaluate RV structure and function. RV systolic pressure (RVSP) was measured using a pressure catheter and Fulton Index (RV/ left ventricle + septum) was measured to evaluate RV hypertrophy (RVH). To explore the mechanisms, a focused PCR array was performed to assess the expression of angiogenic genes in the RV of male and female rats subjected to sham or PAB procedure. RV endothelial cells (RVECs) were isolated from Fischer CDF rats and effects of female sex hormones on angiogenic ability of RVECs was assessed using Matrigel network formation assay. We also assessed the role of sphingosine kinase-1 (Sphk1) inhibitor, PF-543, in mediating the effects of female sex hormones on angiogenic potential of RVECs. Results: At 1- and 2-week post-PAB, RVSP and RVH were significantly elevated in PAB rats compared to control rats; however, no differences were observed between male and female rats. Cardiomyocyte surface area (330 vs 234 mm2, p<0.05) and fibrosis (6.96 vs 4.58%, p<0.05) were both significantly higher in male compared to female rats. RV end-diastolic diameter was also increased in male rats compared to female rats (3.33 vs 2.05 mm; p<0.05). On the contrary, RV function was preserved in female rats as indicated by higher cardiac index and fractional area change compared to male rats. Up-regulation of angiogenic genes, including Sphk1, was observed in the RV of female rats compared to male rats at 2 weeks post-PAB. Estradiol treatment increased network forming ability of RVEC isolated from Fischer CDF rats and this effect was inhibited by PF-543. Conclusions: Female Fischer CDF rats develop adaptive RV remodeling in response to PAB compared to mal-adaptive RV remodeling in male rats. Moreover, the better RV adaptation in female rats involves increased RV angiogenesis and these effect may be mediated through Sphk1. Research Nova Scotia, Dalhousie University This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».