Jin-Zhen Wu

Nanoparticle Drug- and Gene-eluting Stents for the Prevention and Treatment of Coronary Restenosis

Percutaneous coronary intervention (PCI) has become the most common revascularization procedure for coronary artery disease. The use of stents has reduced the rate of restenosis by preventing elastic recoil and negative remodeling. However, in-stent restenosis remains one of the major drawbacks of this procedure. Drug-eluting stents (DESs) have proven to be effective in reducing the risk of late restenosis, but the use of currently marketed DESs presents safety concerns, including the non-specificity of therapeutics, incomplete endothelialization leading to late thrombosis, the need for long-term anti-platelet agents, and local hypersensitivity to polymer delivery matrices. In addition, the current DESs lack the capacity for adjustment of the drug dose and release kinetics appropriate to the disease status of the treated vessel. The development of efficacious therapeutic strategies to prevent and inhibit restenosis after PCI is critical for the treatment of coronary artery disease. The administration of drugs using biodegradable polymer nanoparticles as carriers has generated immense interest due to their excellent biocompatibility and ability to facilitate prolonged drug release. Despite the potential benefits of nanoparticles as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of nanoparticle materials, as well as to their size and shape. This review describes the molecular mechanism of coronary restenosis, the use of DESs, and progress in nanoparticle drug- or gene-eluting stents for the prevention and treatment of coronary restenosis.

Interactions of the Apolipoprotein A5 Gene Polymorphisms and Alcohol Consumption on Serum Lipid Levels

Background Little is known about the interactions of apolipoprotein (Apo) A5 gene polymorphisms and alcohol consumption on serum lipid profiles. The present study was undertaken to detect the interactions of ApoA5–1131T>C, c.553G>T and c.457G>A polymorphisms and alcohol consumption on serum lipid levels. Methodology/Principal Findings A total of 516 nondrinkers and 514 drinkers were randomly selected from our previous stratified randomized cluster samples. Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism. The levels of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), ApoA1 and ApoB were higher in drinkers than in nondrinkers (P<0.05–0.001). The genotypic and allelic frequencies of three loci were not different between the two groups. The interactions between –1131T>C genotypes and alcohol consumption on ApoB levels (P<0.05) and the ApoA1/ApoB ratio (P<0.01), between c.553G>T genotypes and alcohol consumption on low-density lipoprotein cholesterol (LDL-C) levels (P<0.05) and the ApoA1/ApoB ratio (P<0.05), and between c.457G>A genotypes and alcohol consumption on TG levels (P<0.001) were detected by factorial regression analysis after controlling for potential confounders. Four haplotypes (T-G-G, C-G-G, T-A-G and C-G-T) had frequencies ranging from 0.06 to 0.87. Three haplotypes (C-G-G, T-A-G, and C-G-T) were significantly associated with serum lipid parameters. The –1131T>C genotypes were correlated with TG, and c.553G>T and c.457G>A genotypes were associated with HDL-C levels in nondrinkers (P<0.05 for all). For drinkers, the –1131T>C genotypes were correlated with TC, TG, LDL-C, ApoB levels and the ApoA1/ApoB ratio (P<0.01 for all); c.553G>T genotypes were correlated with TC, TG, HDL-C and LDL-C levels (P<0.05–0.01); and c.457G>A genotypes were associated with TG, LDL-C, ApoA1 and ApoB levels (P<0.05–0.01). Conclusions The differences in some serum lipid parameters between the drinkers and nondrinkers might partly result from different interactions of the ApoA5 gene polymorphisms and alcohol consumption.

The proprotein convertase subtilisin/kexin type 9 gene E670G polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

BackgroundProprotein convertase subtilisin-like kexin type 9 (PCSK9) plays a key role in regulating plasma low-density lipoprotein cholesterol (LDL-C) levels. However, the association of E670G (rs505151) polymorphism in the PCSK9 gene and serum lipid levels is inconsistent in several previous studies. The present study was undertaken to detect the association of PCSK9 E670G polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.MethodsA total of 649 subjects of Bai Ku Yao and 646 participants of Han were randomly selected from our previous samples. Genotypes of the PCSK9 E670G polymorphism were determined via polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.ResultsSerum levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), LDL-C, and apolipoprotein (Apo) AI were lower in Bai Ku Yao than in Han (P < 0.01 for all). The frequency of G allele was 2.00% in Bai Ku Yao and 4.80% in Han (P < 0.01). There was significant difference in the genotypic and allelic frequencies between Bai Ku Yao and Han (P < 0.01); between normal LDL-C (≤ 3.20 mmol/L) and high LDL-C subgroups (> 3.20 mmol/L, P < 0.01) in Bai Ku Yao; and between normal HDL-C (≥ 0.91 mmol/L) and low HDL-C (< 0.91 mmol/L, P < 0.05), between normal ApoAI (≥ 1.00 g/L) and low ApoAI (< 1.00 g/L, P < 0.05), or between normal ApoAI/ApoB ratio (≥ 1.00) and low ApoAI/ApoB ratio (< 1.00, P < 0.01) subgroups in Han. The G allele carriers in Han had higher serum HDL-C levels and the ratio of ApoAI to ApoB than the G allele noncarriers. The G allele carriers in Han had higher serum HDL-C and ApoAI levels than the G allele noncarriers in males (P < 0.05 for each), whereas the G allele carriers had lower serum ApoB levels and higher the ratio of ApoAI to ApoB than the G allele noncarriers in females (P < 0.05 for all). Serum HDL-C and ApoAI levels in Han were correlated with genotypes (P < 0.05) in males, and serum ApoB levels and the ratio of ApoAI to ApoB were associated with genotypes (P < 0.05) in females.ConclusionsThe PCSK9 E670G polymorphism is mainly associated with some serum lipid parameters in the Han population. The G allele carriers had higher serum HDL-C and ApoAI levels in males, and lower serum ApoB levels and higher the ApoAI/ApoB ratio in females than the G allele noncarriers.

Association of methylenetetrahydrofolate reductase C677T polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

BackgroundThe association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and serum lipid profiles is still controversial in diverse ethnics. Bai Ku Yao is an isolated subgroup of the Yao minority in China. The aim of the present study was to eveluate the association of MTHFR C677T polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.MethodsA total of 780 subjects of Bai Ku Yao and 686 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of the MTHFR C677T was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.ResultsThe levels of serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (P < 0.05-0.001). The frequency of C and T alleles was 77.4% and 22.6% in Bai Ku Yao, and 60.9% and 39.1% in Han (P < 0.001); respectively. The frequency of CC, CT and TT genotypes was 58.7%, 37.3% and 4.0% in Bai Ku Yao, and 32.6%, 56.4% and 11.0% in Han (P < 0.001); respectively. The levels of TC and LDL-C in both ethnic groups were significant differences among the three genotypes (P < 0.05-0.01). The T allele carriers had higher serum TC and LDL-C levels than the T allele noncarriers. The levels of ApoB in Han were significant differences among the three genotypes (P < 0.05). The T allele carriers had higher serum ApoB levels as compared with the T allele noncarriers. The levels of TC, TG and LDL-C in Bai Ku Yao were correlated with genotypes (P < 0.05-0.001), whereas the levels of LDL-C in Han were associated with genotypes (P < 0.001). Serum lipid parameters were also correlated with sex, age, body mass index, alcohol consumption, cigarette smoking, and blood pressure in the both ethnic groups.ConclusionsThe differences in serum TC, TG, LDL-C and ApoB levels between the two ethnic groups might partly result from different genotypic and allelic frequencies of the MTHFR C677T or different MTHFR gene-enviromental interactions.

Interactions between alcohol intake and the polymorphism of rs708272 on serum high-density lipoprotein cholesterol levels in the Guangxi Hei Yi Zhuang population.

Both alcohol consumption and the polymorphism of the cholesteryl ester transfer protein (CETP) TaqIB gene (rs708272) influence plasma high-density lipoprotein cholesterol (HDL-C) levels. However, their interactions on serum HDL-C levels is not well known. The present study was undertaken to detect the interactions between alcohol consumption and the rs708272 polymorphism on serum lipid levels in the Guangxi Hei Yi Zhuang population. Genotyping of the rs708272 in 342 nondrinkers and 416 drinkers aged 15-70 years was performed by polymerase chain reaction and restriction fragment length polymorphism. Interactions between rs708272 genotype and alcohol consumption was assessed using a cross-product term between genotypes and the aforementioned factor. Statistical significance was evaluated with analysis of co-variance. The frequency of B1 allele was 65.8% in nondrinkers and 64.7% in drinkers (P>.05), respectively. The frequencies of B1B1, B1B2, and B2B2 genotypes were 45.0%, 41.5%, and 13.5% in nondrinkers, and 41.3%, 46.6%, and 12.0% in drinkers (P>.05), respectively. The levels of HDL-C and apolipoprotein (Apo) AI in nondrinkers were higher in B2B2 genotype than in B1B1 genotype (P<.05 for each), whereas triglyceride (TG) levels in drinkers were higher in B1B1 genotype than in B1B2 genotype (P<.05). The levels of TG, HDL-C, Apo AI in B1B1 genotype, and HDL-C and Apo AI in B1B2 genotype were higher in drinkers than in nondrinkers (P<.05-.01), whereas the levels of low-density lipoprotein cholesterol (LDL-C) and Apo B in B2B2 genotype, and the levels of LDL-C in B1B1 genotype were lower in drinkers than in nondrinkers (P<.05-.01). The levels of HDL-C were positively correlated with female sex and genotype in nondrinkers (P<.001 for each), and were positively associated with age and alcohol consumption in drinkers (P<.005 and<.01, respectively). This study suggests that the B1 carriers benefited more from alcohol consumption than the B2 carriers in increasing serum HDL-C and Apo AI levels, and lowering LDL-C levels.

Apolipoprotein E Gene Polymorphism and Serum Lipid Levels in the Guangxi Hei Yi Zhuang and Han Populations

Hei Yi Zhuang is an isolated subgroup of the Zhuang minority in China. Little is known about the distribution of apolipoprotein (apo) E genetic variations and its role in lipid metabolism in this population. The present study was undertaken to compare the effect of apoE gene polymorphism on serum lipid levels between the Guangxi Hei Yi Zhuang and Han populations. A total of 873 subjects of Hei Yi Zhuang and 867 participants of Han Chinese were surveyed by a stratified randomized cluster sampling. Genotyping of apoE was performed using polymerase chain reaction and restriction fragment length polymorphism. The frequencies of  2,  3, and  4 alleles were 15.23%, 79.84%, and 4.93% in Hei Yi Zhuang, and 9.23%, 81.43%, and 9.34% in Han (P < 0.001); respectively. The frequencies of  2/ 2,  2/ 3,  2/ 4,  3/ 3,  3/ 4, and  4/ 4 genotypes were 4.70%, 17.86%, 3.21%, 68.16%, 5.50%, and 0.57% in Hei Yi Zhuang, and 2.54%, 9.23%, 4.15%, 70.70%, 12.23%, and 1.15% in Han (P < 0.001); respectively. Total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and apoB levels were lower in Hei Yi Zhuang than in Han (P < 0.01–0.001), but high-density lipoprotein cholesterol (HDL-C) levels and the ratio of apoA-I to apoB were higher in Hei Yi Zhuang than in Han (P < 0.001 for each). There were significant differences in TC, HDL-C, LDL-C, and apoB levels among the six genotypes in both ethnic groups (P < 0.01–0.001). Hyperlipidemia was positively correlated with age, body mass index, hypertension, alcohol consumption, and apoE allele in both populations (P < 0.05–0.001). TC, LDL-C, and apoB levels were positively correlated, and HDL-C levels were negatively associated with apoE genotypes in both ethnic groups (P < 0.001 for all). The differences in the lipid profiles between Hei Yi Zhuang and Han Chinese might partly attribute to the differences in apoE genotypic and allelic frequencies.

ATP-binding cassette transporter G5 and G8 polymorphisms and several environmental factors with serum lipid levels.

Background The association of ATP-binding cassette (ABC) transporter single nucleotide polymorphisms (SNPs) and serum lipid profiles is inconsistent. The present study was undertaken to detect the association of ABCG5/G8 SNPs and several environmental factors with serum lipid levels. Methodology/Principal Findings Genotyping of the ABCG5 (rs4131229 and rs6720173) and ABCG8 (rs3806471 and rs4148211) SNPs was performed in 719 unrelated subjects of Mulao nationality and 782 participants of Han nationality. There were no differences in the genotypic and allelic frequencies of four SNPs between the two ethnic groups besides the genotypic frequencies of rs4131229 SNP in Han. The levels of triglyceride (TG), apolipoprotein (Apo) A1, and ApoA1/ApoB ratio (rs4131229); low-density lipoprotein cholesterol (LDL-C) and ApoB (rs6720173); high-density lipoprotein cholesterol (HDL-C), ApoA1, ApoB, and ApoA1/ApoB ratio (rs3806471); and HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4148211) in Han were different among their genotypes (P<0.05–0.001). The levels of LDL-C (rs6720173) and ApoA1 (rs3806471) in Mulao were also different among their genotypes (P<0.05 for each). The levels of TC, TG, HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4131229); LDL-C and ApoB (rs6720173); HDL-C, ApoA1, and ApoA1/ApoB ratio (rs3806471); and TG, HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4148211) in Han males; and ApoA1/ApoB ratio (rs4131229); LDL-C, ApoB, and ApoA1/ApoB ratio (rs3806471); HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4148211) in Han females were different between the genotypes (P<0.05–0.001). The levels of LDL-C in Mulao females were also different between GG and GC/CC genotypes of rs6720173 (P<0.05). The correlation between serum lipid parameters and genotypes of four SNPs was observed in Han, especially in Han males. Serum lipid parameters were also correlated with several environmental factors. Conclusions The associations of four ABCG5/G8 SNPs and serum lipid levels are different between the Mulao and Han populations, or between males and females, suggesting that there may be a racial/ethnic- and/or sex-specific association between ABCG5/G8 SNPs and some serum lipid parameters.

Association of apolipoprotein A5 gene polymorphisms and serum lipid levels.

BACKGROUND AND AIMS Apolipoprotein (APO) A5 gene polymorphisms have been associated with increased plasma triglyceride (TG), but the results are inconsistent. The present study was undertaken to detect the APOA5 gene polymorphisms and their associations with lipid profiles in the Guangxi Hei Yi Zhuang and Han populations. METHODS AND RESULTS Genotyping of the APOA5 -1131T>C, c.553G>T and c.457G>A was performed in 490 subjects of Hei Yi Zhuang and 540 participants of Han Chinese aged 15-89 years. The -1131C allele frequency was higher in high total cholesterol (TC) than in normal TC subgroups in both the ethnic groups (P<0.05). The c.553T allele frequency was higher in high TG than in normal TG subgroups (P<0.01), in high APOB than in normal APOB subgroups in Hei Yi Zhuang (P<0.05), or in females than in males in Han (P<0.01). The c.457A allele frequency in Han was higher in high TG than in normal TG subgroups, in low APOA1 than in normal APOA1 subgroups, in males than in females, or in normal APOB than in high APOB subgroups (P<0.05-0.01). The levels of TC, low-density lipoprotein cholesterol and APOB in Hei Yi Zhuang were correlated with -1131T>C genotype or allele, and the levels of TG were associated with c.553G>T genotype (P<0.05). The levels of TG, APOA1 and APOB in Han were correlated with c.457G>A genotype or allele, and the levels of TC were associated with -1131T>C allele (P<0.05). CONCLUSIONS The differences in the lipid profiles between the two ethnic groups might partly result from different APOA5 gene-environmental interactions.

Association of the SPTLC3 rs364585 polymorphism and serum lipid profiles in two Chinese ethnic groups

BackgroundLittle is known about the association of the single nucleotide polymorphism (SNP) of rs364585 near serine palmitoyl-transferase long-chain base subunit 3 gene (SPTLC3) and serum lipid profiles. The present study was detected the association of the SPTLC3 rs364585 SNP and several environmental factors with serum lipid profiles in the Han and Jing populations.MethodsGenotyping of the SPTLC3 rs364585 SNP was performed in 824 unrelated individuals of Han and 783 participants of Jing by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.ResultsThere was no significant difference in either genotypic or allelic frequencies between Han and Jing, or between males and females of the both ethnic groups. The levels of serum low-density lipoprotein cholesterol (LDL-C) and the ratio of apolipoprotein (Apo) A1 to ApoB in Han; and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and LDL-C in Jing were different between the A allele carriers and the A allele non-carriers (P < 0.05-0.001). Subgroup analysis according to sex showed that the levels of LDL-C in Han males; TC and LDL-C in Jing males; and HDL-C and LDL-C in Jing females were different between the A allele carriers and the A allele non-carriers (P < 0.05-0.001), the A allele carriers had higher LDL-C and TC levels, and lower HDL-C levels than the A allele non-carriers. Serum lipid traits were also associated with several environmental factors in the Han and Jing populations, or in males and females of the both ethnic groups.ConclusionsThe present study demonstrates the association between the SPTLC3 rs364585 SNP and serum TC, HDL-C and LDL-C levels in our study populations. These associations might have ethnic- and/or sex-specificity.Trial registrationRetrospectively registered.

Association of the GALNT2 gene polymorphisms and several environmental factors with serum lipid levels in the Mulao and Han populations

BackgroundThe association of UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 2 gene (GALNT2) single nucleotide polymorphisms (SNPs) and serum lipid profiles in the general population is not well known. The present study was undertaken to detect the association of GALNT2 polymorphisms and several environmental factors with serum lipid levels in the Guangxi Mulao and Han populations.MethodA total of 775 subjects of Mulao nationality and 699 participants of Han nationality were randomly selected from our stratified randomized cluster samples. Genotyping of the GALNT2 rs2144300 and rs4846914 SNPs was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.ResultsThere were no significant differences in the genotypic and allelic frequencies of both SNPs between the two ethnic groups, or between the males and females. The subjects with TT genotype of rs2144300 in Mulao had lower serum triglyceride (TG) levels than the subjects with CC genotype in females (P < 0.01). The participants with CT/TT genotype of rs2144300 in Han had lower TG and apolipoprotein (Apo) B levels, and higher high-density lipoprotein cholesterol (HDL-C), ApoA1 levels and the ratio of ApoA1 to ApoB in males; and higher low-density lipoprotein cholesterol (LDL-C) and ApoB levels in females than the participants with CC genotype (P < 0.05-0.001). The individuals with GA/AA genotype of rs4846914 in Mulao had higher total cholesterol (TC) and LDL-C levels than the individuals with GG genotype in males (P < 0.05 for each). The subjects with AA genotype of rs4846914 in Han had higher LDL-C and ApoB levels, and lower HDL-C levels and the ratio of ApoA1 to ApoB than the subjects with GG genotype (P < 0.05 for each). The levels of TC in Mulao were correlated with the genotypes of rs4846914 in males (P < 0.05). The levels of ApoA1 in Han were correlated with the genotypes of both SNPs, and the levels of HDL-C and ApoB and the ratio of ApoA1 to ApoB were associated with the genotypes of rs2144300 in males (P < 0.05-0.001). The levels of LDL-C in Han were correlated with the genotypes of rs4846914 in females (P < 0.05). Serum lipid parameters were also correlated with several enviromental factors.ConclusionsThe associations of both GALNT2 rs2144300 and rs4846914 SNPs and serum lipid levels are different in the Mulao and Han populations. These discrepancies might partly result from different GALNT2 gene-enviromental interactions.