High-altitude chronic hypoxia prevents myocardial dysfunction in experimental model of type 2 diabetes

High-altitude chronic hypoxia (CHH) has a favorable impact on the lower prevalence of diabetes together with the better glucose tolerance. However, whether it prevents diabetic cardiomyopathy remains unclear. This study aimed to investigate the effects of CHH on left ventricular (LV) function in experimental model of type 2 diabetes.

Sprague-Dawley rats were randomly divided into control (altitude 500 m), DM (diabetes mellitus and altitude 500 m), CHH (altitude 4250 m and non-diabetic for 2 weeks), CHH-DM2 (altitude 4250 m and DM for 2 weeks), and CHH-DM8 (altitude 4250 m and DM for 8 weeks) groups. The experimental model of type 2 diabetes was induced by a high-fat diet plus low-dose streptozotocin (35 mg/kg, intraperitoneal) after fasted overnight. Left ventricular cardiac function and global myocardial strain were evaluated at 2, and 8 weeks by 7.0 T cardiovascular magnetic resonance. Subsequently, biochemical indices, histological evaluation, and levels of hypoxia-induced factor (HIF)-1α were assessed.

Left ventricular ejection fraction (LVEF), global longitudinal (GLS), circumferential (GCS), and radial (GRS) strains significantly decreased in the DM group compared with the controls. However, these abnormalities in DM rats were significantly prevented in the CHH-DM2 group, and were further improved in CHH-DM8 group. Mechanistically, prolonged CHH at high altitude further reduced cardiac apoptosis, and oxidative stress, and increased autophagy, and the expression of HIF-1α in diabetic myocardial tissue.

CHH exerted cardioprotective effects by improving LV function, increasing myocardial strain and attenuating cardiac hypertrophy in type 2 diabetic rats, likely through reducing apoptosis and oxidative stress, activating autophagy and HIF-1α signaling in diabetic rats.