Western Diet-Fed, Aortic-Banded Ossabaw Swine

Abstract

Visual Abstract

The right ventricular transcriptome signature in Ossabaw swine with cardiometabolic heart failure: implications for the coronary vasculature

“…This was an analysis of the total RV homogenate (cardiomyocytes, fibroblasts, coronary blood vessels) and right coronary artery (RCA) harvested from the same animals previously used in a recently published study from our laboratory (10). Briefly, intact, female Ossabaw swine (15-20 kg; 2 mo old) were randomly assigned to either a nonsham sedentary control group (CON; n = 5) that ingested a standard chow diet (5L80, Lab Diet; 3.03 kcal • g À1 , carbohydrate = 71%, protein = 18.5%, and fat = 10.5%; 500 g/day) or a Western dietfed aortic-banded heart failure group (WD-AB; n = 4) that consumed a diet high in fat, high fructose corn syrup, and cholesterol [5B4L, Laboratory Diet; 4.14 kcal g À1 ; carbohydrate, 40.8% (17.8% of total calories from high fructose corn syrup); protein, 16.2%; fat, 43%, 2% cholesterol w/w] (10,(20)(21)(22)(23)(24). At 6 mo of age, an aortic band was placed on the ascending aorta to increase afterload on the heart as previously described (10,(13)(14)(15)(16)(17)(25)(26)(27).…”

“…After 6 mo of chronic cardiac pressure overload and 10 mo of Western diet feeding, terminal experiments were performed at 1 yr of age. Animals were anesthetized with a telazol (5 mg/kg)/xylazine (2.25 mg/kg) mix and maintained on propofol (6-10 mg•kg À1 •min À1 with bolus as needed) for previously published in vivo hemodynamic experiments before euthanasia and tissue harvest as previously described (10,20).…”

“…We recently developed a preclinical swine model of cardiometabolic HF that showed aortic-banded Ossabaw pigs fed a Western Diet display an increase in postmortem RV weight compared with lean controls, similar to HF with deterioration of RV structure and function (10). We hypothesized that gene networks associated with hypertrophic remodeling would be activated in the RV of these same animals.…”

“…The RV homogenate assessed herein is composed of a number of cell types including vascular and immune cells, cardiomyocytes, and fibroblasts. Given our laboratory has extensively studied vascular contributions to HF (10)(11)(12)(13)(14)(15)(16)(17), the extension of this study to the coronary vasculature was a logical choice. Our results indicate an increase in JNK1 protein in the RCA that was associated with dysregulation of fibronectin, an extracellular matrix (ECM) component that is a selective target of MAPK8/ JNK1 signaling (18,19).…”

Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Extracellular Matrix Remodeling during Left Ventricular Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

“…The majority of studies used rodents: either mice (12 articles) [37][38][39][40][41][42][43][44][45][46][47][48] or rats (6 articles) [49][50][51][52][53][54]. Other species included swine (n = 3) [55][56][57], rabbit (n = 1) [58] and guinea pig (n = 1) [59]. All but one of the studies employing mice used a C57BL/6 strain or adapted strains with a C57BL/6 background.…”