Effects of iron in food in improving ventricular remodeling in male mice with hypoxic pulmonary hypertension
Objective To investigate the effects of iron in food in improving ventricular remodeling in male mice with hypoxic pulmonary hypertension(HPH).Methods Male mice were randomly divided into a normoxic control group(exposed to an altitude of 2 260 m),a hypoxic control group(exposed to a hypobaric oxygen chamber at a simulated altitude of 5 000 m)and a hypoxic iron-high group(exposed to a hypobaric oxygen chamber a simu-lated altitude of 5 000 m),with 10 mice in each group.Right ventricular systolic pressure(RVSP)was measured by right heart catheterization.Right ventricular hypertrophy index(RVHI)was calculated by using the correlation for-mula.The variations in ventricular tissue and small pulmonary arteries were observed by using HE staining.The percentages of vessel wall area to the total area of the blood vessel(WA%)and the vessel wall thickness to the di-ameter of the blood vessel(WT%)were calculated.Western Blot was adopted to determine the content of carnitine palmitic acyltransferase(CPT1A),ferritin(FTN),transferrin receptor(TFR)and ferroportin(FPN)in the right ven-tricle.The ventricles of mice in the normoxic control group,hypoxic control group and hypoxic iron-high group were analyzed by non-targeted histological analysis using the UPLC-Orbitrap mass spectrometry system.Results Compared with the normoxic control group,RVSP,RVHI,WA%and WT%were elevated in the hypoxic control group(P<0.05);the protein expression level of FPN was reduced(P<0.05),and there was no statistically significant difference in the protein expression levels of TFR,FTN and CPTIA;the arrangement of ventricular myocytes was disorganized and fibrosis was more obvious.Compared with the hypoxic control group,RVSP,RVHI,WA%and WT%in the hypoxic iron-high group were significantly decreased(P<0.05);FPN protein expression levels were in-creased(P<0.05),and there was no statistically difference in TFR,FTN and CPT1A protein expression;ventricular myocardial fibrosis was reduced.Compared with the normoxic control group,there was no significant variation in the vast majority of carnitine derivatives and the metabolic levels of medium and long-chain fatty acids in the right ventricular tissues of mice in the hypoxic control group;the vast majority of carnitine derivatives and the metabolic levels of medium and long-chain fatty acids were reduced in the hypoxic iron-high group,especially unsaturated fatty acids.Conclusions It is possible to improve HPH ventricular remodeling by enhancing myocardial fatty acid oxidation ability through iron in food.