Characterization of cardiac fibrosis in older lean vs. obese male ZSF1 rats

• Published in: Physiology (Bethesda, Md.) Md.), 2024-05, Vol.39 (S1)
• Main Authors: Mooers, Caitlyn, Pallas, Wrenn, Hannan, Johanna, Garvin, Alexandra
• Format: Article
• Language: English
• ISSN: 1548-9213; 1548-9221
• DOI: 10.1152/physiol.2024.39.S1.1917

Abstract only The ZSF1 rat is a novel strain produced by crossing a ZDF (Zucker diabetic fatty) female and SHHF (Spontaneously Hypertensive Heart Failure) male rat. Offspring of this hybrid have two phenotypes: healthy lean or obese prone to diabetes and heart failure. The metabolic syndrome and hypertension displayed by the obese ZSF1 rat mimics that seen in individuals who are predisposed to heart failure with preserved ejection fraction (HFpEF). Historically, HFpEF is a diffcult disease to accurately model with rodents and the ZSF1 rat is a promising model for the spontaneous progression to HFpEF. In recent studies, the oldest age at which ZSF1 rats were studied was 32 weeks and these obese rats displayed diastolic dysfunction, cardiac fibrosis, and hypertrophy. Since the prevalence of HFpEF increases with advanced age, the aim of the current study is to evaluate the extent of fibrosis in older ZSF1 rats (40-42 weeks) and determine whether this age group is more appropriate for the study of fibrotic cardiac remodeling related to HFpEF. We hypothesize that left ventricular (LV) fibrosis and collagen gene expression will be increased in obese compared to lean counterparts. Furthermore, we expect that the extent of fibrosis in this age group will exceed that reported in 32-week-old rats; thus, providing an improved model for the study of fibrotic heart disease. Lean and obese male ZSF1 rats (n=8/group) were aged to 40-42 weeks. Rats were anesthetized with a ketamine/xylazine cocktail and cardiac function was evaluated by invasive hemodynamics. The heart was removed, and the LV was trimmed and weighed. A mid-myocardial section from the LV was fixed and embedded in paraffn for histology. Remaining LV tissue was frozen for extraction of RNA and protein for biochemical analysis. LV collagen was assessed by Sirius red stain and collagen I ( Col1a1) and III ( Col3a1) gene expression were assessed by RTqPCR. With no significant difference in heart rate, obese ZSF1 rats had higher LV developed pressure compared to lean (191.1 vs. 122.0 mmHg, p