Abstract Body: Authors: Anza Ali¹, Vineet Sharma², M.S, Yuriana Aguilar ^1,2, PhD
1. Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University 2. Department of Biomedical Engineering, College of Engineering, Texas A&M University

Background: Type II Diabetes (T2D) is a major risk factor for cardiovascular diseases, specifically heart failure with preserved ejection fraction (HFpEF). Patients with HF have a downregulated expression of striated muscle preferentially expressed gene (SPEG), a key kinase protein with multiple downstream structural, mechanical, and metabolic substrates. However, its role in HFpEF remains yet to be assessed.
Objective: The goal of this study was to assess changes in SPEG levels during HFpEF progression using a diet induced mouse model at 5 and 10 weeks.
Methods: T2D was induced in mice using high-fat diet (HFD, 60% fat) in conjunction with L-NAME to induce HFpEF. Mice were split into 2 cohorts and placed on control diets or HFD+L-NAME for 5 or 10 weeks. Echocardiography, and glucose tolerance test (GTT) was performed for cardiac function and induction of diabetes respectively, and mice hearts were harvested for molecular biology to determine SPEG expression at gene and protein level.
Data: Significant increase in glucose levels as per area under the curve (AUC) at 5-week (1738.8 ± 378.7 vs 935.1 ± 229.5) and 10-week (2690.4 ± 627.3 vs 1687.7 ± 187.8) on HFD+L-NAME diet as compared to their respective controls indicated induction of T2D. Interestingly, qPCR data showed reduced SPEG mRNA levels at both 5-week (0.356 ± 0.199 vs 1.033 ± 0.292) and 10-week (0.716 ± 0.283 vs 1.000 ± 0.169) cohorts as compared to their respective controls. We also observed increased heart weight to tibial length (HW/TL) ratio in the 5 weeks cohort (7.75 ± 0.94 vs 7.40 ± 1.20 mg/mm) and 10 weeks (8.69 ± 2.06 vs 7.20 ± 0.81 mg/mm) as compared to their respective controls, indicative of cardiac hypertrophy.
Conclusion: Our study provides groundwork for establishing progression-based differences in the calcium handling protein, SPEG, in a diabetic induced HFpEF model. This evaluation helps pave the way for future studies involving lipid nanoparticle mediated SPEG delivery in vitro and in vivo to restore SPEG functionality and prevent HFpEF disease progression.