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High density lipoprotein cholesterol ( HDL-C) has received extensive attention because of its cardiovascular protective effects.Recent studies showed that HDL could promote reverse cholesterol transport ( RCT ) , be anti-inflammatory and antioxidant, and induce angiogenesis. Apolipoptrotein A-I (apoA-I), the most abundant protein of HDL, plays a pivotal role in the HDL mediated-functional activities.Short peptides based on the amphiphilic alpha helix structure of apoA-I have been designed and aimed at imitating the function of apoA-I.The function and metabolism of these mimetic peptides depend on their amino acids component and sequence , and have been proved to exert protection in against cardiovascular disease , infection, inflammation and oxidative damage, metabolic syndrome and tumor.Clinical trials confirmed their benefits, but high cost put them out of the practical applications..
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ObjectiveTo investigate the role of iNOS in the middle and late stage of pulmonary hypertension (PH) and the effect of L-Arginine(L-Arg) on these stage.MethodsThirty healthy male SD rats were randomly divided into five groups.All rats except those in control group were injected intraperitoneally (ip) with a single dose (50 mg/kg) of MCT to induce PH.Then the L3 and L5 groups were injected ip with 500 mg/kg L-Arg daily for 3 weeks and 5weeks respectively,the M3 and M5groups received a daily ip injection of the same amount of saline as L-Arg for 3 weeks and 5 weeks respectively; the same amount of saline was injected ip daily in control group for 5 weeks.Right ventricular systolic pressure(RVSP) was measured before lungs were excised for immunohistochemistry at the end of experiments. ResultsThe expressions of iNOS and elastin in M3 and M5 were higher compared to the control group,but L-Arg partly reduced the expressions of iNOS and elastin both at 3weeks and 5 weeks post-MCT.The reduction of eNOS expression in L3 and L5 groups were lower compared to M3 and M5 groups,but the eNOS expression in L3 and L5 groups were still lower than control group.ConclusionDuring the middle and late stage of PH,the expression of eNOS was decreased.The expression of iNOS was induced,which would produce numerous NO.However,these NO had no benefit on the development of PH.L-Arg could restore the balance of eNOS and iNOS,and could inhibit the development of PH,which may provide a new clues to explore the pathogenesis and treatment of PH.
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AIM:To investigate the mechanism of endothelium-derived microparticles(EMP)-induced endothelial dysfunction and the role of superoxide anion(O-?2) in EMP-induced endothelial dysfunction.METHODS:EMP were isolated from human umbilical vein endothelial cells stimulated with plasminogen activated inhibitor-1.(1) Cultured bovine aortic endothelial cells(BAEC) were divided into 3 groups and pretreated with nothing in group 1,EMP(1?108/L) in group 2,EMP(1?108/L) + L-nitroarginiemethylester(L-NAME,1 mmol/L) in group 3 for 30 min and A23187(5 ?mol/L) stimulated O-?2 generation was determined by superoxide dismutase(SOD)-inhibitable ferricytochrome C reduction.(2) Facialis arteries(60-150 microns) were isolated from C57BL/6 mice and divided into 4 groups.The vessels were pretreated with nothing in group 1,EMP(1?108/L) in group 2,EMP(1?108/L) + SOD(2?105 U/L) in group 3,EMP(1?108/L) + polyethylene glycolated-SOD(PEG-SOD,2?105 U/L) in group 4 for 10 min and acetylcholine(ACH)-induced vasodilation was measured.RESULTS:(1) EMP significantly increased O-?2 generation in BAEC culture,which was prevented about 50% by pretreating the BAEC with L-NAME.(2) EMP significantly impaired ACH-induced vasodilation.SOD could not restore EMP-impaired ACH-induced vasodilation and PEG-SOD showed partial restoration of vasodilation.CONCLUSION:These data indicate that at least some EMP-induced endothelial dysfunction occurs by inducing intracellular O-?2 generation.It may provide a theoretical evidences in finding a multiple treatment including removal of O-?2 in the future.