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The microsomal triglyceride transfer protein (MTP) catalyzes the transfer of triglyceride, cholesteryl ester, and phosphatidylcholine between phospholipid surfaces. The 97-kD subunit imparts lipid transfer activity and thus plays a role in the assembly of apolipoprotein B (apoB)-containing lipoproteins. We tested whether polymorphisms in the promoter region of the large subunit of the MTP gene might be related to different plasma lipid variables, atherosclerosis, and the risk of myocardial infarction (MI). We screened 838 bp in the promoter region of the MTP gene by PCR-SSCP and identified two polymorphisms at positions −400 (MTP/−400 (A→t)) and −164 (MTP/−164 (T→c)), the latter being situated on a putative sterol responsive element (SRE) consensus sequence. The two polymorphisms, investigated in 622 male patients with MI and in 728 age-matched controls participating in the ECTIM Study, were in nearly complete linkage disequilibrium (|D′| = ′0.98, less frequent alleles being preferentially associated, P < 0.001). There were no significant differences in genotype or allele frequencies between patients with MI and controls. Moreover, no significant associations between the two promoter polymorphisms and several lipid variables measured in the control groups of the ECTIM Study or coronary artery stenosis, angiographically assessed in patients with MI, were detected. We conclude that these MTP polymorphisms are unrelated to lipid variables or coronary heart disease in this study.—Herrmann, S-M., O. Poirier, V. Nicaud, A. Evans, J-B. Ruidavets, G. Luc, D. Arveiler, C. Bao-Sheng, and F. Cambien. Identification of two polymorphisms in the promoter of the microsomal triglyceride transfer protein (MTP) gene: lack of association with lipoprotein profiles. J. Lipid Res. 1998. 39: 2432–2435.

Abstract Background Tree shrew and beijing duck are regarded as animal models resistant to atherosclerosis (AS). This study was carried out to discover the potential mechanism. Methods Blood samples were collected from healthy men and male animals. Plasma lipid profile and activities of cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) were measured, compared and analyzed in human, tree shrew, and Beijing duck. Results The results showed that there were species differences on plasma lipid profile and activities of CETP and PLTP in the three species. Compared with human, tree shrew and beijing duck had higher high density lipoprotein cholesterol (HDL-C)/total cholesterol (TC) and HDL-C/low density lipoprotein cholesterol (LDL-C) ratios, but lower CETP and PLTP activities. In the three species, CETP and PLTP activities were negatively related with the ratio of HDL-C/LDL-C. Conclusions The present study suggested that low plasma CETP and PLTP activities may lead to a high HDL-C/LDL-C ratio and a high resistance to AS finally in tree shrew and beijing duck. Moreover, low PLTP activity may also make the animals resistant to AS by the relative high vitamin E content of apoB-containing lipoproteins and high anti-inflammatory and antioxidative properties of HDL particles. A detailed study in the future is recommended.

cDNA fragments that were differentially expressed between human oesophageal carcinomas and matched normal adjacent mucosa were isolated using an improved mRNA differential display technique. One of them was identified as the 3′-untranslated region of SPRR3 and was homologous to the esophagin cDNA. Northern blot, dot blot and reverse transcription–polymerase chain reaction (RT–PCR) analyses revealed that SPRR3 expression was lost in three cell lines of oesophageal carcinoma and was dramatically decreased in 54 out of 57 primary oesophageal carcinomas compared with adjacent normal mucosa. Esophagin has been shown to be down-regulated in western oesophageal carcinomas. The data suggest that esophagin is probably the protein product of the gene SPRR3 and that altered mRNA expression of SPRR3/esophagin is a frequent event in the development of Chinese oesophageal cancer. [ABSTRACT FROM PUBLISHER]

Objective To explore the efficacy of ganoderma lucidum preparation(Ling Zhi) in treating APP/PS-1 transgenic mouse models of Alzheimer's disease(AD).Methods APP/PS-1 transgenic mice of 4 months were randomly divided into model group,ganoderma lucidum treatment groups,including high [2250 mg/(kg·d)] and middle [750 mg/(kg·d)] dose groups,i.e.LZ-H and LZ-M groups,and the positive control group(treated with donepezil hydrochloride [2 mg/(kg·d)]).In addition,C57BL/6J wild mice were selected as normal group.The animals were administered for 4 months.Histopathological examinations including hematoxylin-eosin(HE) staining,immunohistochemistry,special staining,and electron microscopy were applied,and then the pathological morphology and structures in different groups were compared. Results The senile plaques and neurofibrillar tangles in the cerebrum and cerebellum were dissolved or disappeared in LZ-H and LZ-M groups.Decrease of amyloid angiopathy was found in LZ-H and LZ-M groups.The immature neurons appeared more in hippocampus and dentate nucleus of LZ-H and LZ-M groups than those in AD model and donepezil hydrochloride groups(hippcampus:F=1.738,P=0.016;dentate nucleus:F=1.924,P=0.026),and these immature neurons differentiated to be neurons.More Purkinje cells loss occurred in AD model mice than that in LZ-H and LZ-M groups(F=9.46,P=0.007;F=9.46,P=0.010).The LZ-H and LZ-M groups had more new neuron stem cells grown up in cerebellum.Electromicroscopic examination showed the hippocampal neurons in LZ-H and LZ-M group were integrated,the nuclear membrane was intact,and the mitochondria in the cytoplasm,endoplasmic reticulum,Golgi bodies,microtubules,and synapses were also complete.The microglial cell showed no abnormality.No toxicity appeared in the pathological specimens of mice treated with ganoderma lucidum preparation.Conclusion The ganoderma lucidum preparation can dissolve and decline or dismiss the senile plaques and neurofibrillar tangles in the brain of AD mice and also reduce the amyloid angiopathy.

Objective: To determine the anti-inflammatory functions of different cysteine mutants of apolipoprotein A-I recombinant HDLs., Methods: The recombinant HDLs (named rHDL52, rHDL107, rHDL173, rHDLwt) were reconstituted by mixing wild types or their mutants with dipalmitoyl phosphatidylcholine. And the in vivo effects on lipopolysaccharide (LPS)-induced endotoxemia were examined in mice. The plasma levels of plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in by ELISA were tested. And we also set up two control groups: LPS and saline., Results: The rHDL52 mice had a significant decrease of plasma TNF-alpha and IL-1beta and the protection of lung against acute injury. 24 h post-injection as compared with rHDLwt group [TNF-alpha: (135.28 +/- 12.84) pg/ml, IL-1beta: (82.00 +/- 8.19) pg/ml], the rHDL52 mice exhibited a higher capability of lowering the plasma levels of TNF-alpha and IL-1beta [(39.66 +/- 2.44) pg/ml, (66.83 +/- 6.24) pg/ml, both P < 0.05]. And, as indicated by histological sections of lung tissue, the rHDL52 mice could also lower the infiltration of inflammatory cells in lung., Conclusion: rHDL52 has a higher anti-inflammation capability than wild type rHDLwt.

Objective: To determine the anti-inflammatory functions of different cysteine mutants of apolipoprotein A-I recombinant HDLs., Methods: The authors reconstituted recombinant HDLs (namely rHDL74, rHDL129, rHDL195 and rHDL228) by mixing wild type or those mutants with dipalmitoyl phosphatidylcholine and examined their in vivo effects upon LPS-induced endotoxemia in mice., Results: At 24 h post-injection, mice receiving rHDL74 [TNF-alpha: (24 +/- 3) pg/ml; IL-1beta: (45 +/- 5) pg/ml] had a significant decrease of plasma tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) as compared with control mice receiving either saline or rHDLwt [TNF-alpha: (135 +/- 12) pg/ml; IL-1beta: (82 +/- 8) pg/ml, P < 0.05]. Administration of rHDL74 to mice injected with LPS also led to a protection of lung against acute injury and attenuation of endotoxin-induced clinical symptoms in mice as compared with controls injected with LPS only., Conclusion: Compared with rHDLwt, rHDL74 exhibits higher anti-inflammation capabilities. And it may be a potential clinical candidate for therapy for endotoxin-induced septic shock.

Objective: To investigate the relationship between the plasma biomarker proteins and the states of Zang-Fu organs in patients with phlegm or blood stagnation syndromes due to hyperlipidemia and atherosclerosis., Methods: The states of Zang-Fu organs in 146 patients with hyperlipidemia and atherosclerosis were diagnosed by syndrome differentiation of traditional Chinese medicine. The plasma proteins from these patients were separated by two-dimensional polyacrylamide gel electrophoresis (2-DE). Differential protein profiling was established by Image Master 6.0 software, and the differential proteins were analyzed by quadrupole time of flight mass spectrometry (Q-TOF-MS). The association between the plasma biomarker proteins and the states of Zang-Fu organs was analyzed by graphical models., Results: The biomarker proteins such as fibrinogen gamma chain, albumin and apolipoprotein AI (precursor) in discrimination of the patients with phlegm syndrome from phlegm accumulating with stagnation syndrome were correlated with the deficiency of kidney-qi, heart-qi and spleen-qi. Among the four biomarker proteins in discrimination of the patients with phlegm syndrome from blood stagnation syndrome, albumin, adrenomedullin binding protein (precursor) and haptoglobin (precursor) were correlated with the deficiency of kidney-qi and heart-qi, but complement component C4 was independent of the deficient Zang-Fu organs. The biomarker albumin was associated with the deficiency of kidney-qi, heart-qi and spleen-qi, and adrenomedullin binding protein (precursor) was correlated with the deficiency of spleen-qi in discrimination of the patients with blood stagnation syndrome from phlegm accumulating with stagnation syndrome. As the potential biomarker proteins in discrimination of the patients with non-phlegm and non-stagnation syndrome from phlegm accumulating with stagnation syndrome, the fibrinogen beta chain was related with the deficiency of kidney-qi, and apolipoprotein AI (precursor) was correlated with both the deficiency of kidney-qi and heart-qi., Conclusion: There exists inherent correlation between the states of Zang-Fu organs and the plasma probable biomarker proteins in the patients with different phlegm or blood stagnation syndromes due to hyperlipidemia and atherosclerosis.

Background: Familial hypercholesterolemia (FH), caused by low density lipoprotein (LDL) receptor (LDL-R) gene mutations, is associated with increased risk of premature coronary heart disease. Until now, limited molecular data concerning FH are available in China. The present study described the clinical profiles and cell biological defects of a Chinese FH kindred with novel LDL-R gene mutation., Methods: The patient's LDL-R gene coding region was sequenced. The patient's lymphocytes were isolated and the LDL-R expression, binding and up-take functions were observed by immunohistochemistry staining and flow cytometry detection. The patient's heart and the major large vessels were detected by vessel ultrasound examination and myocardial perfusion imaging (MPI)., Results: The patient's LDL-R expression, LDL binding and up-take functions were significantly lower than normal control (39%, 63% and 76% respectively). A novel homozygous 1439 C-->T mutation of the LDL-R gene was detected in the patient and his family. ECG showed atypical angina pectoris. Echocardiogram showed stenosis of the coronary artery and calcification of the aortic valve and its root. Blood vessel ultrasound examination showed the thickness of large vessel intima, and the vessel lumen was narrowed by 71%. MPI showed ischemic changes., Conclusions: The LDL-R synthesis dysfunction of FH patients leads to arterial stenosis and calcification, which are the major phenotype of the clinical disorder. The mutation of the LDL-R gene is determined. These data increase the mutational spectrum of FH in China.

Aim: To clone human cholesteryl ester transfer protein (CETP) cDNA, express and purify human CETP in E.coli and prepare CETP-specific rabbit antiserum., Methods: by RT-PCR method, the encoding sequence of human cholesteryl ester transfer protein (CETP) was cloned into pET-30b(+) vector. Then BL21 (DE3) of E.coli transformed with recombinant vector pET-CETP was induced to express CETP in high level by IPTG. The expressed protein was purified from SDS-polyacrylamide gel, and the antiserum against CETP was raised in rabbit. The titer and specificity of rabbit antiserum were evaluated by ELISA, Western blot and immunofluorescence assay., Results: The results of SDS-PAGE showed that CETP was expressed in the form of inclusion bodies in BL21(DE3) and the best expression time was about 4 hours. The titer of the rabbit antiserum prepared with CETP purified from SDS-PAGE was 1:5. 12 x 10(5) and the antiserum reacted specifically with CETP expressed in BL21 (DE3) and COS7 cells., Conclusion: The preparation of the specific rabbit antiserum against CETP will be valuable for the study on the structure and function of human CETP.

Apolipoprotein, an important component of the lipoproteins, modulates the activity of enzyme, introduces the binding of cell receptor and lipoproteins, and keeps the structural stability of lipoproteins. The amphipathic helices structure in apolipoproteins is the structural basis that it binds and transports lipids. A certain envelope glycoprotein (gp) in the outer membrane of HIV also has been found to be with such amphipathic helices structure. Recent studies have shown that the liposome consisted of apolipoproteins and phospholipids may defend against HCV, HIV, and herpes simplex virus, and even neutralize the endotoxin released by bacteria. The liposome made up of apolipoproteins and phospholipid has became a potential carrier for anti-tumor and anti-virus drugs.

Objective: To study the distribution, frequency and structure of variable number of tandem repeats (VNTR) in 3' region of apoB gene in Chinese population., Methods: Genomic DNA was extracted from peripheral blood obtained under consent from randomly-chosen 522 individuals who came to the hospital for physical examination, and used to screen for polymorphisms of 3' VNTR of the apoB gene by employing polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), gradient polyacrylamide gel electrophoresis, cloning and sequencing., Results: Sixteen types of alleles of apoB 3oVNTR were identified, among which heterozygotes were more than homozygotes. The biggest allele is HVE58, and the smallest one is HVE22. HVE34 had the highest frequency (40.4%), followed by HVE32 (34.7%). This showed significant difference from the allelic distribution of other populations (Caucasian and Swedish). Through sequencing of 60 alleles, a new isomer (Y-A=ATAATTAAATATTT) and four new types of alleles were found., Conclusion: The Chinese population we studied had a higher frequency of small alleles and showed a difference in allelic structure and frequency distribution from European and American in this populations.