Biology and Medicine

Abstrait

The Effect of Glucagon-like Peptide-1 Receptor Agonist (GLP1RA) on Hypertensive Induced Heart Failure with Preserved Ejection Fraction and Hypertensive Cardiomyopathy

Zhe Yu Zhang1, Song-Yan Liao1,2, Zhe Zhen1, Sijia Sun1, Wing-Hon Lai1, Anita Tsang1, Jo Jo Siu-Han Hai1*

Recent preclinical data suggest that Glucagon-like Peptide-1 Receptor Agonist (GLP1RA) possesses cardioprotective properties against the pathophysiology of Hypertension (HT). We sought to unravel the potential therapeutic application of GLP1RA in a clinically relevant large animal model of hypertensive Cardiomyopathy (hCMP). We used a combination of Angiotensin II (Ang II) and Deoxycorticosterone Acetate (DOCA) pellets to induce sustained HT status and establish hCMP in porcine model. Changes in cardiac echocardiography, invasive hemodynamic parameters, neurohumoral biomarkers and inflammationrelated cytokines were investigated in 23 adult pigs, among which 6 were serving as control, 9 were induced with HT, and the remaining 8 were HT-induced with GLP1RA treatment. Eight weeks after the study initiated, HT pigs have developed sustained high Blood Pressure (BP) at both systole and diastole. Phenotype of hCMP has also become significant as impairment in systolic/diastolic function left ventricular remodeling and cardiac hypertrophy was determined by echocardiogram and invasive hemodynamics. Additionally, blood Norepinephrine (NE) content, venoarterial NE gradient and pro-inflammatory cytokines in HT pigs were increased. GLP1RA treatment halted the elevation in BP, left ventricular remodeling and cardiac hypertrophy development; preserved the left ventricular systolic/diastolic function; reduced the venoarterial NE gradient and decreased pro-inflammatory cytokine levels in the hCMP pigs at 18 weeks. Our results demonstrate that GLP1RA treatment has a remarkable effect effect on reducing blood pressure and inflammation, and improving left ventricular function, thus indicating its potential therapeutic value in hypertension-induced heart failure in a large animal model of hCMP.