LOW-DOSE FOLIC ACID PROTECTS AGAINST ADVERSE CARDIAC REMODELING IN SPONTANEOUSLY HYPERTENSIVE RATS WITH HYPERHOMOCYSTEINEMIA

Abstract

Objective: The interaction between hypertension and hyperhomocysteinemia (Hhcy) leads to adverse myocardial and coronary vascular remodeling in the hypertensive heart, resulting in impaired diastolic function. Folic acid (FA) is a free radical scavenger with antioxidant properties that effectively reduces homocysteine (Hcy) levels. The aim of this study was to evaluate whether lowering plasma homocysteine (Hcy) with different dose of folic acid (FA) could against Hhcy-induced myocardial injury in spontaneously hypertensive rats (SHRs) and its possible mechanisms. Design and method: Thirty-two adult male SHRs were randomly divided into four groups (n = 8/group), namely control group, Hhcy intervention group, Hhcy + Low-dose FA treatment group (0.4 mg/Kg·d), Hhcy + High-dose FA treatment group (4 mg/Kg·d), and then three Hhcy groups were subcutaneously injected 2% DL- homocysteine 5 ml/Kg. FA intervention started after 4 weeks’ Hcy injection. The total duration of the trial was 16 weeks. Cardiac echocardiography was performed at the last week. The Systolic blood pressure (SBP), diastolic blood pressure (DBP), plasma Hcy, serum malondialdehyde (MDA), superoxide dismutase (SOD) were measured, and Masson's trichrome stain to enable evaluation of collagen deposition under a microscope. Furthermore, the levels of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) protein were detected by extraction of nuclear protein from cardiac tissue. Results: Intragastric administration of FA significantly reduced plasma Hcy levels. Serum SOD was significantly increased and serum MDA were also significantly attenuated by FA. Low-dose folic acid is more effective than high-dose folic acid in relieving Hhcy-induced anomalies in the heart of SHRs, such as the decline in cardiac diastolic function, perivascular collagen accumulation, and arteriolar wall thickening. FA increased the expression of Nrf2 and HO-1, and exhibited a protective effect against Hhcy-induced oxidative stress (OS), and there were no significant difference between high-dose and low-dose FA groups. Conclusions: Low-dose FA treatment can better protect against Hhcy-induced myocardial injury in SHRs, which may be due to its inhibition of OS and upregulation of Nrf2/HO-1 pathway.