This study aimed to investigate whether pitavastatin protected against injury induced by advanced glycation end products products（AGEs） in neonatal rat cardiomyocytes,and to examine the underlying mechanisms.Cardiom...This study aimed to investigate whether pitavastatin protected against injury induced by advanced glycation end products products（AGEs） in neonatal rat cardiomyocytes,and to examine the underlying mechanisms.Cardiomyocytes of neonatal rats were incubated for 48 hours with AGEs（100 μg/mL）,receptor for advanced glycation end products（RAGE）,antibody（1 μg/mL） and pitavastatin（600 ng/mL）.The levels of p62 and beclinl were determined by Western blotting.Mitochondrial membrane potential（△Ψm） and the generation of reactive oxygen species（ROS） were measured through the JC-1 and DCFH-DA.In the AGEs group,the expression of beclinl was remarkably increased compared to the control group,while the expression of p62 was significantly decreased.AGEs also markedly decreased △Ψm and significantly increased ROS compared with the control group.After treatment with RAGE antibody or pitavastatin,the level of beclinl was markedly decreased compared with the AGEs group,but the level of p62 was remarkably increased.In the AGEs ＋ RAGE antibody group and AGEs＋ pitavastatin group,△Ψm was significantly increased and ROS was remarkably decreased compared with the AGEs group.In conclusion,AGEs-RAGE may induce autophagy of cardiomyocytes by generation of ROS and pitavastatin could protect against AGEs-induced injury against cardiomyocytes.展开更多
It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein(LDL)cholesterol(LDL-C),but its impact on lipoprotein subfractions and oxidized low-density lipoprotein(oxLDL)has not been det...It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein(LDL)cholesterol(LDL-C),but its impact on lipoprotein subfractions and oxidized low-density lipoprotein(oxLDL)has not been determined.The aim of the present study was to investigate the potential effects of pitavastatin on subfractions of LDL and high-density lipoprotein(HDL)as well as oxLDL in untreated patients with coronary atherosclerosis(AS).Thirty-six subjects were enrolled in this study.O f them,18 patients with AS were administered pitavastatin 2 mg/day for 8 weeks and 18 healthy subjects without therapy served as controls.The plasma lipid profile,lipoprotein subfractions and circulating oxLDL were determined at baseline and 8 weeks respectively.The results showed that pitavastatin treatment indeed not only decreased LDL-C,total cholesterol(TC),triglycerides(TG)and apolipoprotein B(ApoB)levels,and increased HDL cholesterol(HDL-C),but also reduced the cholesterol concentration of all of the LDL subfractions and the percentage of intermediate and small LDL subfractions.Meanwhile,pitavastatin could decrease plasma oxLDL levels.Furthermore,a more close correlation was found between oxLDL and LDL-C as well as LDL subfractions after pitavastatin treatment.We concluded that a moderate dose of pitavastatin therapy not only decreases LDL-C and oxLDL concentrations but also improves LDL subfractions in patients with AS.展开更多
An electrochemically pretreated silver macroporous(Ag MP) multiwalled carbon nanotube modified glassy carbon electrode(PAN-Ag MP-MWCNT-GCE) was fabricated for the selective determination of an antihyperlipidimic drug,...An electrochemically pretreated silver macroporous(Ag MP) multiwalled carbon nanotube modified glassy carbon electrode(PAN-Ag MP-MWCNT-GCE) was fabricated for the selective determination of an antihyperlipidimic drug, pitavastatin(PST). The fabricated electrochemical sensor was characterized by cyclic voltammetry(CV) and electrochemical impedance spectroscopy(EIS). The fabricated electrode was employed in quantifying and determining PST through differential pulse adsorptive stripping voltammetry(DPAdSV) and CV. The electrode fabrication proceeded with remarkable sensitivity to the determination of PST. The effect of various optimized parameters such as pH, scan rate(ν), accumulation time(t_(acc)), accumulation potential(U_(acc))and loading volumes of Ag MP-MWCNT suspension were investigated to evaluate the performance of synthesized electrochemical sensor and to propose a simple, accurate, rapid and economical procedure for the quantification of PST in pharmaceutical formulations and biological fluids. A linear response of PST concentration in the range 2.0×10^(-7)–1.6×10^(-6)M with low detection(LOD) and quantification(LOQ) limits of 9.66 ± 0.04 nM and 32.25 ± 0.07 nM, respectively, were obtained under these optimized conditions.展开更多
Background： Statins have proven efficacy in inhibiting the onset and progress of atherosclerosis. The effectiveness of pitavastatin in reversing carotid atherosclerosis associated with hypercholesterolemia （HC） is ...Background： Statins have proven efficacy in inhibiting the onset and progress of atherosclerosis. The effectiveness of pitavastatin in reversing carotid atherosclerosis associated with hypercholesterolemia （HC） is un-known. Objectives： To explore the simultaneous effects of pitavastatin calcium on brachial arterial flow-mediated vasodilatation （FMD）, carotid intima-media thickness （IMT）, and arterial stiffness （β）, three surrogate markers of ath-erosclerosis were studied in HC patients. Methods：A randomized, double-blind trial was performed with 40 HC sub-jects who fulfil ed the inclusion/exclusion criteria. Patients were given pitavastatin calcium 1 mg/d （Group 1） or 2 mg/d （Group 2） for 8 weeks. There were 20 patients in each group, and 30 gender-and age-matched healthy subjects as controls were recruited. FMD of the brachial artery, carotid IMT, and arterial stiffness indicated byβwere measured at baseline and at 8 weeks after starting pitavastatin calcium therapy using ultrasound techniques. Biochemical tests were also made on al subjects. Results： At baseline, higher total cholesterol （TC） and low-density lipoprotein cho-lesterol （LDL-C）, reduced FMD, and increasedβand IMT were observed in HC patients （P0.05）. Significant negative interactions between TC/LDL and FMD （P〈0.05–0.001）, positive interactions between TC and IMT （P=0.003） and between TC/LDL and β （P〈0.001–0.000） were found. Conclusions： Treatment with pitavastatin calcium exerted fa-vorable effects on endothelial function and arterial stiffness. It also improved carotid atherosclerosis in patients with HC.展开更多
Arapid,selective and sensitive liquid chromatography-tandem massspectrometry(LC-MS/MS)method has been developed and validated for the determination of pitavastatin in humanplasma.Following a liquid-liquid extraction,b...Arapid,selective and sensitive liquid chromatography-tandem massspectrometry(LC-MS/MS)method has been developed and validated for the determination of pitavastatin in humanplasma.Following a liquid-liquid extraction,both the analytes and internal standard telmisartan were separated on a Luna C_(18) column with a mobile phase consisted of acetonitrile-methanol-1% formic acid in water(50:25:25,v/v/v).Mass spectrometric detection involved electrospray ionization in the positive ion mode followed by multiple reaction monitoring(MRM)of the transitions at m/z 421.9→290.1 for pitavastatin and m/z 515.2→276.2 for the IS.The assay for pitavastatin showed good linearity(r≥0.99)over the ranges 0.2-400 ng/ml,with a lower limit of quantitation of 0.2 ng/ml.Accuracy and precision for the assay were determined by calculating the intra-and inter-batch variation of quality control(QC)samples at three concentration levels,with relative standard deviations(RSD)of less than 15%for both analytes.The mean extraction recovery of pitavastatin and IS were both above 70%.Matrix effect hasn't been found in this method.The method has been successfully applied to a clinic pharmacokinetic study of pitavastatin administered.展开更多
Degradation pathway for pitavastatin calcium is established as per ICH recommendations by validated and stability indicating reverse phase liquid chromatographic method. Pitavastatin is subjected to stress conditions ...Degradation pathway for pitavastatin calcium is established as per ICH recommendations by validated and stability indicating reverse phase liquid chromatographic method. Pitavastatin is subjected to stress conditions of acid, base, oxidation, thermal and photolysis. Significant degradation is observed in acid and base stress conditions. Four impurities are studied among which impurity-4 is found prominent degradant. The stress samples are assayed against a qualified reference standard and the mass balance is found close to 99.5%. Efficient chromatographic separation is achieved on a BEH C18 stationary phase with simple mobile phase combination delivered in gradient mode and quantification is carried at 245 nm at a flow rate of 0.3 mL min-1. In the developed UPLC method the resolution between pitavastatin calcium and four potential impurities is found to be greater than 4.0. Regression analysis shows an r value (correlation coefficient) of greater than 0.998 for pitavastatin calcium and four potential impurities. This method is capable to detect the impurities of pitavastatin calcium at a level of 0.006% with respect to test concentration of 0.10 mg/mL for a 2-μL injection volume. The developed UPLC method is validated with respect to specificity, linearity & range, accuracy, precision and robustness for impurities determination and assay determination.展开更多
Pitavastatin is a strong statin that was developed in Japan. The clinical impact of pitavastatin treatment in patients with ischemic stroke has not been reported. We conducted a prospective, open label, clinical case-...Pitavastatin is a strong statin that was developed in Japan. The clinical impact of pitavastatin treatment in patients with ischemic stroke has not been reported. We conducted a prospective, open label, clinical case-control study to determine the secondary preventive effects of pitavastatin for patients with cerebral infarction and hyperlipidemia. The pitavastatin group included 20 Japanese patients diagnosed with cerebral infarction and hyperlipidemia without previous statin intake. The control group included 22 patients diagnosed with cerebral infarction without hyperlipidemia. The pitavastatin group of patients received 2 mg of pitavastatin once a day after dinner. The mean age of the patients was 69.3 and 75.5 years for the pitavastatin and control groups, respectively, and the age of the pitavastatin group was significantly younger than that of the control group (P < 0.05). The serum TCho and LDL-C levels significantly decreased two months after the initiation of pitavastatin treatment. The mean and maximum intima-media thickness (IMT) also decreased after the initiation of pitavastatin. The mean and maximum IMT did not show any significant changes in the control group. The change of IMT %/year was less than zero for the pitavastatin group, and was almost zero or higher for the control group. Pitavastatin showed beneficial effects by improving the surrogate makers of stroke. These surrogate makers were effective to evaluate the efficacy of pitavastatin to prevent secondary stroke. Although a prospective randomized study is required to elucidate the long-term effects of pitavastatin, the current study suggests that pitavastatin may be effective to prevent secondary stroke in patients with stroke and hyperlipidemia.展开更多
Objectives:According to the findings of randomized controlled trials,blood lipid levels in patients with coronary heart disease(CHD)can be significantly decreased through a combination of pitavastatin and ezetimibe;ho...Objectives:According to the findings of randomized controlled trials,blood lipid levels in patients with coronary heart disease(CHD)can be significantly decreased through a combination of pitavastatin and ezetimibe;however,the effects and clinical applications of this treatment remain controversial.This meta-analysis was aimed at objectively assessing the efficacy and safety of pitavastatin and ezetimibe in lowering blood lipid levels.Design:Relevant studies were retrieved from electronic databases,including PubMed,Cochrane Library,Embase,China National Knowledge Infrastructure,VIP,and WanFang Data,from database inception to June 8,2022.The lev-els of low-density lipoprotein cholesterol,total cholesterol,triglycerides,and high-density lipoprotein cholesterol in patients’serum after treatment were the primary endpoint.Results:Nine randomized controlled trials(2586 patients)met the inclusion criteria.The meta-analysis indi-cated that pitavastatin plus ezetimibe resulted in significantly lower levels of LDL-C[standardized mean difference(SMD)=-0.86,95%confidence interval(CI)(-1.15 to-0.58),P<0.01],TC[SMD=-0.84,95%CI(-1.10 to-0.59),P<0.01],and TG[SMD=-0.59,95%CI(-0.89 to-0.28),P<0.01]than pitavastatin alone.Conclusions:Pitavastatin plus ezetimibe significantly decreased serum LDL-C,TC,and TG levels in patients with CHD.展开更多
Advanced atherosclerosis is the major global cause of death,as featured by the aggregation of apoptotic cells(ACs)in necrotic cores.The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are t...Advanced atherosclerosis is the major global cause of death,as featured by the aggregation of apoptotic cells(ACs)in necrotic cores.The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are the main reasons for forming necrotic cores in advanced atherosclerosis.In this study,we constructed self-assembled procyanidins(PC)NPs for loading pitavastatin(Pita).The designed HA@PC@Pita NPs with hyaluronic acid(HA)modification combined the advantages of efferocytosis restoration of Pita and cholesterol efflux enhancement of PC.In vitro assay indicated that HA@PC@Pita NPs could induce M1/M2 repolarization and upregulate ERK5/Mertk expression to restore efferocytosis of macrophages.Simultaneously,HA@PC@Pita NPs notably promoted cholesterol efflux by promoting macrophage lipophagy,a selective autophagy of lipid droplets.In vivo study showed that HA@PC@Pita NPs cleared necrotic core and enhanced plaque stability in the ApoE^(-/-)mice model with advanced atherosclerosis.Taken together,this study demonstrated the potential of HA@PC@Pita NPs for the treatment of advanced atherosclerosis.展开更多
基金supported by the National NaturalScience Foundation of China(NSFC 81570328,Wang Junhong)the"Sixth-Peak Talent"of Jiangsu Province(2011WSN-029 to Prof.Guo Yan and2013WSN-036 to Dr.Wang Junhong)support by the Health Department of Jiangsu Province(z201301)
文摘This study aimed to investigate whether pitavastatin protected against injury induced by advanced glycation end products products（AGEs） in neonatal rat cardiomyocytes,and to examine the underlying mechanisms.Cardiomyocytes of neonatal rats were incubated for 48 hours with AGEs（100 μg/mL）,receptor for advanced glycation end products（RAGE）,antibody（1 μg/mL） and pitavastatin（600 ng/mL）.The levels of p62 and beclinl were determined by Western blotting.Mitochondrial membrane potential（△Ψm） and the generation of reactive oxygen species（ROS） were measured through the JC-1 and DCFH-DA.In the AGEs group,the expression of beclinl was remarkably increased compared to the control group,while the expression of p62 was significantly decreased.AGEs also markedly decreased △Ψm and significantly increased ROS compared with the control group.After treatment with RAGE antibody or pitavastatin,the level of beclinl was markedly decreased compared with the AGEs group,but the level of p62 was remarkably increased.In the AGEs ＋ RAGE antibody group and AGEs＋ pitavastatin group,△Ψm was significantly increased and ROS was remarkably decreased compared with the AGEs group.In conclusion,AGEs-RAGE may induce autophagy of cardiomyocytes by generation of ROS and pitavastatin could protect against AGEs-induced injury against cardiomyocytes.
基金This work was supported,in part,by Capital Special Foundation of Clinical Application Research(No.Z121107001012015)Capital Health Development Fund(No.201614035)+1 种基金CAMS Major Collaborative Innovation Project(No.2016-I2M-1-011)PUMC Youth Fund(No.3332018200).
文摘It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein(LDL)cholesterol(LDL-C),but its impact on lipoprotein subfractions and oxidized low-density lipoprotein(oxLDL)has not been determined.The aim of the present study was to investigate the potential effects of pitavastatin on subfractions of LDL and high-density lipoprotein(HDL)as well as oxLDL in untreated patients with coronary atherosclerosis(AS).Thirty-six subjects were enrolled in this study.O f them,18 patients with AS were administered pitavastatin 2 mg/day for 8 weeks and 18 healthy subjects without therapy served as controls.The plasma lipid profile,lipoprotein subfractions and circulating oxLDL were determined at baseline and 8 weeks respectively.The results showed that pitavastatin treatment indeed not only decreased LDL-C,total cholesterol(TC),triglycerides(TG)and apolipoprotein B(ApoB)levels,and increased HDL cholesterol(HDL-C),but also reduced the cholesterol concentration of all of the LDL subfractions and the percentage of intermediate and small LDL subfractions.Meanwhile,pitavastatin could decrease plasma oxLDL levels.Furthermore,a more close correlation was found between oxLDL and LDL-C as well as LDL subfractions after pitavastatin treatment.We concluded that a moderate dose of pitavastatin therapy not only decreases LDL-C and oxLDL concentrations but also improves LDL subfractions in patients with AS.
文摘An electrochemically pretreated silver macroporous(Ag MP) multiwalled carbon nanotube modified glassy carbon electrode(PAN-Ag MP-MWCNT-GCE) was fabricated for the selective determination of an antihyperlipidimic drug, pitavastatin(PST). The fabricated electrochemical sensor was characterized by cyclic voltammetry(CV) and electrochemical impedance spectroscopy(EIS). The fabricated electrode was employed in quantifying and determining PST through differential pulse adsorptive stripping voltammetry(DPAdSV) and CV. The electrode fabrication proceeded with remarkable sensitivity to the determination of PST. The effect of various optimized parameters such as pH, scan rate(ν), accumulation time(t_(acc)), accumulation potential(U_(acc))and loading volumes of Ag MP-MWCNT suspension were investigated to evaluate the performance of synthesized electrochemical sensor and to propose a simple, accurate, rapid and economical procedure for the quantification of PST in pharmaceutical formulations and biological fluids. A linear response of PST concentration in the range 2.0×10^(-7)–1.6×10^(-6)M with low detection(LOD) and quantification(LOQ) limits of 9.66 ± 0.04 nM and 32.25 ± 0.07 nM, respectively, were obtained under these optimized conditions.
基金Project supported by the National Science and Technology Major Project(No.2012ZX09303-016-003)the National Natural Science Foundation of China(Nos.81270352,81270287,81300168,81471036,and 81470560)
文摘Background： Statins have proven efficacy in inhibiting the onset and progress of atherosclerosis. The effectiveness of pitavastatin in reversing carotid atherosclerosis associated with hypercholesterolemia （HC） is un-known. Objectives： To explore the simultaneous effects of pitavastatin calcium on brachial arterial flow-mediated vasodilatation （FMD）, carotid intima-media thickness （IMT）, and arterial stiffness （β）, three surrogate markers of ath-erosclerosis were studied in HC patients. Methods：A randomized, double-blind trial was performed with 40 HC sub-jects who fulfil ed the inclusion/exclusion criteria. Patients were given pitavastatin calcium 1 mg/d （Group 1） or 2 mg/d （Group 2） for 8 weeks. There were 20 patients in each group, and 30 gender-and age-matched healthy subjects as controls were recruited. FMD of the brachial artery, carotid IMT, and arterial stiffness indicated byβwere measured at baseline and at 8 weeks after starting pitavastatin calcium therapy using ultrasound techniques. Biochemical tests were also made on al subjects. Results： At baseline, higher total cholesterol （TC） and low-density lipoprotein cho-lesterol （LDL-C）, reduced FMD, and increasedβand IMT were observed in HC patients （P0.05）. Significant negative interactions between TC/LDL and FMD （P〈0.05–0.001）, positive interactions between TC and IMT （P=0.003） and between TC/LDL and β （P〈0.001–0.000） were found. Conclusions： Treatment with pitavastatin calcium exerted fa-vorable effects on endothelial function and arterial stiffness. It also improved carotid atherosclerosis in patients with HC.
基金This work was supported by Qidu Pharmaceutical Co.,LTD(Zibo,China).
文摘Arapid,selective and sensitive liquid chromatography-tandem massspectrometry(LC-MS/MS)method has been developed and validated for the determination of pitavastatin in humanplasma.Following a liquid-liquid extraction,both the analytes and internal standard telmisartan were separated on a Luna C_(18) column with a mobile phase consisted of acetonitrile-methanol-1% formic acid in water(50:25:25,v/v/v).Mass spectrometric detection involved electrospray ionization in the positive ion mode followed by multiple reaction monitoring(MRM)of the transitions at m/z 421.9→290.1 for pitavastatin and m/z 515.2→276.2 for the IS.The assay for pitavastatin showed good linearity(r≥0.99)over the ranges 0.2-400 ng/ml,with a lower limit of quantitation of 0.2 ng/ml.Accuracy and precision for the assay were determined by calculating the intra-and inter-batch variation of quality control(QC)samples at three concentration levels,with relative standard deviations(RSD)of less than 15%for both analytes.The mean extraction recovery of pitavastatin and IS were both above 70%.Matrix effect hasn't been found in this method.The method has been successfully applied to a clinic pharmacokinetic study of pitavastatin administered.
文摘Degradation pathway for pitavastatin calcium is established as per ICH recommendations by validated and stability indicating reverse phase liquid chromatographic method. Pitavastatin is subjected to stress conditions of acid, base, oxidation, thermal and photolysis. Significant degradation is observed in acid and base stress conditions. Four impurities are studied among which impurity-4 is found prominent degradant. The stress samples are assayed against a qualified reference standard and the mass balance is found close to 99.5%. Efficient chromatographic separation is achieved on a BEH C18 stationary phase with simple mobile phase combination delivered in gradient mode and quantification is carried at 245 nm at a flow rate of 0.3 mL min-1. In the developed UPLC method the resolution between pitavastatin calcium and four potential impurities is found to be greater than 4.0. Regression analysis shows an r value (correlation coefficient) of greater than 0.998 for pitavastatin calcium and four potential impurities. This method is capable to detect the impurities of pitavastatin calcium at a level of 0.006% with respect to test concentration of 0.10 mg/mL for a 2-μL injection volume. The developed UPLC method is validated with respect to specificity, linearity & range, accuracy, precision and robustness for impurities determination and assay determination.
文摘Pitavastatin is a strong statin that was developed in Japan. The clinical impact of pitavastatin treatment in patients with ischemic stroke has not been reported. We conducted a prospective, open label, clinical case-control study to determine the secondary preventive effects of pitavastatin for patients with cerebral infarction and hyperlipidemia. The pitavastatin group included 20 Japanese patients diagnosed with cerebral infarction and hyperlipidemia without previous statin intake. The control group included 22 patients diagnosed with cerebral infarction without hyperlipidemia. The pitavastatin group of patients received 2 mg of pitavastatin once a day after dinner. The mean age of the patients was 69.3 and 75.5 years for the pitavastatin and control groups, respectively, and the age of the pitavastatin group was significantly younger than that of the control group (P < 0.05). The serum TCho and LDL-C levels significantly decreased two months after the initiation of pitavastatin treatment. The mean and maximum intima-media thickness (IMT) also decreased after the initiation of pitavastatin. The mean and maximum IMT did not show any significant changes in the control group. The change of IMT %/year was less than zero for the pitavastatin group, and was almost zero or higher for the control group. Pitavastatin showed beneficial effects by improving the surrogate makers of stroke. These surrogate makers were effective to evaluate the efficacy of pitavastatin to prevent secondary stroke. Although a prospective randomized study is required to elucidate the long-term effects of pitavastatin, the current study suggests that pitavastatin may be effective to prevent secondary stroke in patients with stroke and hyperlipidemia.
文摘Objectives:According to the findings of randomized controlled trials,blood lipid levels in patients with coronary heart disease(CHD)can be significantly decreased through a combination of pitavastatin and ezetimibe;however,the effects and clinical applications of this treatment remain controversial.This meta-analysis was aimed at objectively assessing the efficacy and safety of pitavastatin and ezetimibe in lowering blood lipid levels.Design:Relevant studies were retrieved from electronic databases,including PubMed,Cochrane Library,Embase,China National Knowledge Infrastructure,VIP,and WanFang Data,from database inception to June 8,2022.The lev-els of low-density lipoprotein cholesterol,total cholesterol,triglycerides,and high-density lipoprotein cholesterol in patients’serum after treatment were the primary endpoint.Results:Nine randomized controlled trials(2586 patients)met the inclusion criteria.The meta-analysis indi-cated that pitavastatin plus ezetimibe resulted in significantly lower levels of LDL-C[standardized mean difference(SMD)=-0.86,95%confidence interval(CI)(-1.15 to-0.58),P<0.01],TC[SMD=-0.84,95%CI(-1.10 to-0.59),P<0.01],and TG[SMD=-0.59,95%CI(-0.89 to-0.28),P<0.01]than pitavastatin alone.Conclusions:Pitavastatin plus ezetimibe significantly decreased serum LDL-C,TC,and TG levels in patients with CHD.
基金supported by the Open Program of NHC Key Laboratory of Metabolic Cardiovascular Diseases Research,Yinchuan,Chinathe Natural Science Foundation of Hunan Province(2022JJ40698,China)+2 种基金the National Natural Science Foundation of China for Regional Projects(82060264,82260142)Key Research and Development Projects in Ningxia Province(2018BEG02004,China)The“Phoenix Introduction Plan”Talent Startover Project of The Second Affiliated Hospital of Air Force Medical University(2023YFJH011,China).
文摘Advanced atherosclerosis is the major global cause of death,as featured by the aggregation of apoptotic cells(ACs)in necrotic cores.The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are the main reasons for forming necrotic cores in advanced atherosclerosis.In this study,we constructed self-assembled procyanidins(PC)NPs for loading pitavastatin(Pita).The designed HA@PC@Pita NPs with hyaluronic acid(HA)modification combined the advantages of efferocytosis restoration of Pita and cholesterol efflux enhancement of PC.In vitro assay indicated that HA@PC@Pita NPs could induce M1/M2 repolarization and upregulate ERK5/Mertk expression to restore efferocytosis of macrophages.Simultaneously,HA@PC@Pita NPs notably promoted cholesterol efflux by promoting macrophage lipophagy,a selective autophagy of lipid droplets.In vivo study showed that HA@PC@Pita NPs cleared necrotic core and enhanced plaque stability in the ApoE^(-/-)mice model with advanced atherosclerosis.Taken together,this study demonstrated the potential of HA@PC@Pita NPs for the treatment of advanced atherosclerosis.
