Targeting myeloperoxidase to stabilize unruptured aneurysm: an imaging-guided approach.

Inflammation plays a key role in pathogenesis and rupture of aneurysms. Non-invasively and dynamically monitoring aneurysm inflammation is critical. This study evaluated myeloperoxidase (MPO) as an imaging biomarker and therapeutic target for aneurysm inflammation using an elastase-induced rabbit model treated with or without 4-aminobenzoic acid hydrazide (ABAH), an irreversible inhibitor of MPO. Myeloperoxidase-sensitive magnetic resonance imaging (MRI) using Mn-TyrEDTA, a peroxidase activity-dependent contrast agent, revealed weak contrast enhancement in contralateral arteries and decreased contrast enhancement in aneurysm walls with ABAH treatment, indicating MPO activity decreased and inflammation mitigated. This was supported by reduced immune cell infiltration, matrix metalloproteinases (MMP-2 and - 9) activity, ROS production and arterial wall destruction on histology. Finally, the aneurysm expansion rate remained < 50% throughout the study in the ABAH(+) group, but increased gradually in the ABAH(-) group. Our results suggest that inhibition of MPO attenuated inflammation and expansion of experimental aneurysm and MPO-sensitive MRI showed promise as a noninvasive tool for monitoring aneurysm inflammation.

Mn(II) Complex of Lipophilic Group-Modified Ethylenediaminetetraacetic Acid (EDTA) as a New Hepatobiliary MRI Contrast Agent.

Liver-specific contrast agents (CAs) can improve the Magnetic resonance imaging (MRI) detection of focal and diffuse liver lesions by increasing the lesion-to-liver contrast. A novel Mn(II) complex, Mn-BnO-TyrEDTA, with a lipophilic group-modified ethylenediaminetetraacetic acid (EDTA) structure as a ligand to regulate its behavior in vivo, is superior to Gd-EOB-DTPA in terms of a liver-specific MRI contrast agent. An MRI study on mice demonstrated that Mn-BnO-TyrEDTA can be rapidly taken up by hepatocytes with a combination of hepatobiliary and renal clearance pathways. Bromosulfophthalein (BSP) inhibition imaging, biodistribution, and cellular uptake studies confirmed that the mechanism of hepatic targeting of Mn-BnO-TyrEDTA is the hepatic uptake of the amphiphilic anion contrast agent mediated by organic anion transporting polypeptides (OATPs) expressed by functional hepatocytes.

Size and PEG Length-Controlled PEGylated Monocrystalline Superparamagnetic Iron Oxide Nanocomposite for MRI Contrast Agent.

OBJECTIVE: PEGylated superparamagnetic iron oxide (SPIO) is the most promising alternatives to gadolinium-based contrast agents (GBCAs) in MRI. This paper is to explore the imaging effects of PEGylated SPIO, which is influenced by particle sizes and surface polyethylene glycol (PEG) coating, using as MRI contrast agents at different magnetic field intensities. METHODS: Firstly, nine PEGylated monocrystalline SPIO nanoparticles with different nanocrystal sizes and different molecular weights PEG coating were prepared, and then physical and biological properties were analyzed. Finally, MRI imaging in vivo was performed to observe the imaging performance. RESULTS: Nine PEGylated monocrystalline SPIO nanoparticles have good relaxivities, serum stability, and biosecurity. At the same time, they show different imaging characteristics at different magnetic field intensities. Eight-nanometer SPIO@PEG5k is an effective T 2 contrast agent at 3.0 T (r 2/r 1 = 14.0), is an ideal T 1-T 2 dual-mode contrast agent at 1.5 T (r 2/r 1 = 6.52), and is also an effective T 1 contrast agent at 0.5 T (r 2/r 1 = 2.49), while 4-nm SPIO@PEG5k is a T 1-T 2 dual-mode contrast agent at 3.0 T (r 2/r 1 = 5.24), and is a useful T 1 contrast agent at 0.5 T (r 2/r 1 = 1.74) and 1.5 T (r 2/r 1 = 2.85). MRI studies in vivo at 3.0 T further confirm that 4-nm SPIO@PEG5k displays excellent T 1-T 2 dual-mode contrast enhancement, whereas 8-nm SPIO@PEG5k only displays T 2 contrast enhancement. CONCLUSION: PEGylated SPIOs with different nanocrystal sizes and PEG coating can be used as T 1, T 2, or T 1-T 2 dual-mode contrast agents to meet the clinical demands of MRI at specific magnetic fields.

Preparation of Fibroblast Suppressive Poly(ethylene glycol)-b-poly(l-phenylalanine)/Poly(ethylene glycol) Hydrogel and Its Application in Intrauterine Fibrosis Prevention.

Intrauterine adhesions (IUA) often occur as a result of trauma to the basal layer after curettage, postpartum hemorrhage, or surgical miscarriage. Endometrial fibrosis is the primary pathological feature of IUA. The characteristic features of IUA include excessive deposition and reorganization of the extracellular matrix, replacing the normal endometrium. To prevent uterine fibrosis after injury, we prepared and evaluated a type of fibroblast suppressive hydrogel. Poly(ethylene glycol)-b-poly(l-phenylalanine) (PEBP) copolymers were successfully synthesized by ring opening polymerization of l-Phenylalanine N-carboxyanhydride, initiated by methoxy-poly(ethylene glycol)-amine. Injectable PEBP/PEG hydrogels were subsequently formed through π-π accumulations between PEBP macromolecules and hydrogen bonds among PEBP, PEG, and H2O molecules. PEBP/PEG hydrogel could suppress the proliferation of fibroblasts due to the action of l-Phe, released sustainably from PEBP/PEG gels. Lastly, the in vivo preventive effect of PEBP/PEG hydrogel on fibrosis was evaluated in a rat uterine curettage model. It was found that PEBP/PEG hydrogel suppressed uterine fibrosis caused by curettage and promoted embryo implantation in injured uterine by regulating the expression and interactions of transforming growth factor beta 1 (TGF-ß1) and Muc-4. PEBP/PEG hydrogels have the potential for application in uterine adhesion prevention owing to their fibrosis preventive and pregnancy promotiing effects on uterine tissue after injury.

Electrosprayed nanoparticles of poly(p-dioxanone-co-melphalan) macromolecular prodrugs for treatment of xenograft ovarian carcinoma.

Ovarian cancer is considered to be the most fatal reproductive cancers. Melphalan is used to treat ovarian cancer as an intraperitoneal chemotherapy agent. However, elucidating its pharmacokinetic behavior and preparing it for administration are challenging since it undergoes spontaneous hydrolysis. In this study, melphalan is transformed into a macromolecular prodrug by copolymerizing with p-dioxanone. The hydrophobicity of copolymer chains protects melphalan from hydrolysis. Poly(p-dioxanone-co-melphalan; PDCM) is electrosprayed and converted into nanoparticles (PDCM NPs) with diameters of ~300-350 nm to facilitate its intracellular delivery. UPLC-MS and HPLC are applied to verify and monitor the release of melphalan from PDCM NPs. PDCM NPs could suppress the proliferation of SKOV-3 cells. The IC50 of 4.3% melphalan-containing PDCM-3 NP was 70 mg/L, 72 h post administration. These suppression characteristics not only affected by the degradation and then the extracellular release of melphalan from PDCM NPs, but also the uptake via phagocytosis phenomenon in SKOV-3 cells. As revealed by flow cytometry, phagocytosis is a first-order process. Once phagocytosed, PDCM NPs are digested by lysosomes, causing a rapid release of melphalan into the cytoplasm, which ultimately causes suppression of SKOV-3 cell proliferation. Finally, the in vivo antitumor effects of PDCM NPs are verified in xenograft ovarian carcinoma. After a 20-day treatment, the tumor growth rate of the PDCM-3 NP group was (266 ± 178%) which was lower than those in the free melphalan group (367 ± 150%) and control group (648 ± 149%). Besides, significant tissue necrosis and growth suppression were observed in animals administered injections of PDCM NPs. Furthermore, the in vivo tracing results of Nile red-labeled PDCM NPs demonstrated that PDCM-3 NPs might be phagocytosed by macrophages and then taken to adjacent lymph nodes, which is a way of prevention or early treatment of lymphatic metastasis of tumors.

Mn(ii) chelate-coated superparamagnetic iron oxide nanocrystals as high-efficiency magnetic resonance imaging contrast agents.

In this communication, a paramagnetic bifunctional manganese(ii) chelate ([Mn(Dopa-EDTA)]2-) containing a catechol group is designed and synthesized. The catechol can bind iron ions on the surface of superparamagnetic iron oxide (SPIO) nanocrystals to form core-shell nanoparticles. Both 4 and 7 nm SPIO@[Mn(Dopa-EDTA)]2- show good water solubility, single-crystal dispersion, and low cytotoxicity. The study of the interplay between the longitudinal and transverse relaxation revealed that 4 nm SPIO@[Mn(Dopa-EDTA)]2- with lower r 2/r 1 = 1.75 at 0.5 T tends to be a perfect T 1 contrast agent while 7 nm SPIO@[Mn(Dopa-EDTA)]2- with a higher r 2/r 1 = 15.0 at 3.0 T tends to be a T 2 contrast agent. Interestingly, 4 nm SPIO@[Mn(Dopa-EDTA)]2- with an intermediate value of r 2/r 1 = 5.26 at 3.0 T could act as T 1-T 2 dual-modal contrast agent. In vivo imaging with the 4 nm SPIO@[Mn(Dopa-EDTA)]2- nanoparticle shows unique imaging features: (1) long-acting vascular imaging and different signal intensity changes between the liver parenchyma and blood vessels with the CEMRA sequence; (2) the synergistic contrast enhancement of hepatic imaging with the T 1WI and T 2WI sequence. In summary, these Fe/Mn hybrid core-shell nanoparticles, with their ease of synthesis, good biocompatibility, and synergistic contrast enhancement ability, may provide a useful method for tissue and vascular MR imaging.

Anti-Adhesive, Platelet Gathering Effects of c-RGD Modified Poly(p-dioxanone-co-l-Phe) Electrospun Membrane and Its Comprehensive Application in Intestinal Anastomosis.

Intestinal resection and anastomosis are performed in over a million people with various bowel diseases annually. Excessive fibrosis and anastomotic site leakage are the main complications of anastomosis surgery, despite great improvements in operative technique and equipment in recent years. In this study, cRGD modified poly(p-dioxanone-co-l-Phe) (PDPA) membranes are designed and applied in intestinal anastomosis to simultaneously solve the two aforementioned complications. cRGD is modified onto PDPA membranes through both physical absorption and π-π accumulation between d-Phe of cRGD and l-Phe of PDPA. Although cRGD modification enhanced the biocompatibility of PDPA membranes, cRGD modified PDPA membrane suppresses fibroblast proliferation both in vitro and in vivo as a result of degradation and subsequent release of fibroblast suppressive l-Phe from PDPA. Meanwhile, platelets are entrapped by cRGD modified PDPA membranes through the specific binding of cRGD and platelet GPIIbIIIa . cRGD modified PDPA membranes are applied in rat intestinal anastomosis, and both adhesion and stenosis are successfully prevented at anastomotic sites. At the same time, bursting pressure, which represents healing intensity at anastomotic sites, is promoted. The gathering and activation of platelets on PDPA membranes induce secretion of autologous PDGF and VEGF to facilitate angiogenesis and subsequent healing of anastomotic sites.

A novel triarylboron based ratiometric fluorescent probe for in vivo targeting and specific imaging of cancer cells expressing abnormal concentration of GGT.

Abnormal expression of γ-glutamyltranspeptidase (GGT) in living organisms is closely associated with tumorigenesis. However, few reported fluorescence probes can specifically respond to abnormal concentration of GGT. Here, by functionalizing triarylboron moiety with three GGT-specific substrate (GSH) units, a novel fluorescence probe, TAB-3-GSH, was developed for detecting GGT. The results showed that TAB-3-GSH selectively responds to abnormally high levels of GGT (100-1000 U/L) rather than to normal GGT levels (<100 U/L) with ratiometric readout, since the amide linkage can be further hydrolyzed under high GGT levels. TAB-3-GSH was also capable of differentiating GGT-overexpressing ovarian cancer cells from normal cells, because of an improvement in the probe's cell membrane permeability upon reaction with GGT. Moreover, the probe could achieve selective imaging of SKOV-3 tumor site in xenograft mice model. Thus, TAB-3-GSH is a promising probe for tumor targeting in vivo.

Application of Triarylboron Substituted with Cyclic Arginine-Glycine-Aspartic Acid Motifs as a Multivalent Two-Photon Fluorescent Probe for Tumor Imaging in Vivo.

Detection of cancer in its early stages is difficult, and this is a major issue that impairs the timely diagnosis and treatment of tumors. Integrin αVß3 is expressed on tumoral endothelial cells, as well as other tumor cells. By functionalizing the triarylboron (TAB) compound with multiple cyclic arginine-glycine-aspartic acid (cRGD) motifs, which specifically bind to integrin αVß3, a multivalent two-photon fluorescent probe TAB-3-cRGD was designed and chemically synthesized. Through cell imaging experiments, we showed that TAB-3-cRGD can selectively bind to integrin αVß3 on the cell surface and can effectively distinguish normal cells from tumor cells overexpressing integrin αVß3. Using a mouse model, we also showed that TAB-3-cRGD could target the tumor site in vivo, offering a promising tool for cancer detection.

PLGA/PLCA casting and PLGA/PDPA electrospinning bilayer film for prevention of postoperative adhesion.

Postoperative adhesion is a common complication and preventing adhesions during or immediately after operation is particularly important. The application of solid barrier materials represents the most successful clinical strategy to prevent postoperative adhesion. However, a simple physical barrier effect might be insufficient in preventing adhesion satisfactorily. Multilayered structures can be designed with an outer layer as the barrier and an inner layer to respond to relative drug release. In this article, bilayer film composed of a PLGA/PLCA casting layer as barrier and PLGA/PDPA electrospinning layer to respond to the release of anti-fibrosis drug l-Phe was designed and synthesized. The adhesion prevention effect of the above PLGA/PLCA/PDPA bilayer film was examined and compared with single PLGA/PLCA casting film and single PLGA/PDPA electrospinning film by applying rabbit sidewall defect-cecum abrasion model. As demonstrated by histological observation and immunohistochemical analysis, the bilayer film was the most effective of the three films in postoperative adhesion prevention in terms of both physical barrier effect and anti-fibrosis effect of the PDPA macromolecular prodrug. Besides anti-fibrosis effect, PDPA could also suppress excess proliferation of vascular endothelial cells and microvessel caused by long-term stimulation of implantation materials to the surrounding tissues. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2030-2039, 2019.

The in vivo anti-fibrotic function of calcium sensitive receptor (CaSR) modulating poly(p-dioxanone-co-l-phenylalanine) prodrug.

In present study, the apoptosis induction and proliferation suppression effects of l-phenylalanine (l-Phe) on fibroblasts were confirmed. The action sites of l-Phe on fibroblasts suppression were deduced to be calcium sensitive receptor (CaSR) which could cause the release of endoplasmic reticulum (ER) Ca2+ stores; disruption of intracellular Ca2+ homeostasis triggers cell apoptosis via the ER or mitochondrial pathways. The down-regulation of CaSR were observed after the application of l-Phe, and the results those l-Phe triggered the increasing of intracellular Ca2+ concentration and calcineurin expression, and then the apoptosis and increasing G1 fraction of fibroblasts have verified our deduction. Hence, l-Phe could be seen as a kind of anti-fibrotic drugs for the crucial participation of fibroblast in the occurrence of fibrosis. And then, poly(p-dioxanone-co-l-phenylalanine) (PDPA) which could prolong the in-vivo anti-fibrotic effect of l-Phe for the sustained release of l-Phe during its degradation could be treated as anti-fibrotic polymer prodrugs. Based on the above, the in vivo anti-fibrotic function of PDPA was evaluated in rabbit ear scarring, rat peritoneum lipopolysaccharide, and rat sidewall defect/cecum abrasion models. PDPA reduced skin scarring and suppressed peritoneal fibrosis and post operation adhesion as well as secretion of transforming growth factor-ß1 in injured tissue. These results indicate that PDPA is an effective agent for preventing fibrosis following tissue injury. STATEMENT OF SIGNIFICANCE: We have previously demonstrated that poly(p-dioxanone-co-l-phenylalanine) (PDPA) could induce apoptosis to fibroblast and deduced that the inhibitory effect comes from l-phenylalanine. In present study, the inhibition mechanism of l-phenylalanine on fibroblast proliferation was demonstrated. The calcium sensitive receptor (CaSR) was found to be the action site. The CaSR was downregulated after the application of l-phenylalanine, and then the ER Ca2+ stores were released. The released Ca2+ can simultaneously activate Ca2+/calcineurin and then trigger apoptosis and G1 arrest of fibroblast. Hence, l-phenylalanine could be seen as anti-fibrosis drug and PDPA which conjugate l-phenylalanine by hydrolytic covalent bonds could be seen as l-phenylalanine polymer prodrug. Based above, the in vivo anti-fibrotic function of PDPA were verified in three different animal models.

Expression and clinical significance of galectin 3 in bladder cancer tissues and its effect on malignant biological behavior of T24 cells / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the expression of galectin-3 in bladder cancer tissues and its correlation with clinicopathological characteristics of bladder cancer patients, as well as to explore its effect on the proliferation, invasion and apoptosis of bladder cancer T24 cells. Methods:Atotal of 104 cases of pathologically confirmed bladder cancer tissues and the corresponding adjacent tissues were collected from the patients treated at the Affiliated Hospital of North Sichuan Medical College from May 2014 to June 2016. Immunohistochemistry staining was used to determine the galectin-3 protein expression in both cancer and adjacent tissues, and the correlations between galectin-3 expression and clinical pathological features were analyzed. siRNA-Gal3 and siRNA-Control were transfected into T24 cell, respectively. The expression of galectin-3 protein was detected by Western blotting, the proliferation of cells was detected by MTT assay; the invasion of cells was detected by Transwell assay; and the cell apoptosis was determined by Flow cytometry. Results: The positive rate of galectin-3 in bladder cancer tissues was significantly higher than that in adjacent tissues (73.1% vs 9.6%, P<0.05). The expression of galectin-3 in bladder cancer was correlated with histological grade, depth of invasion, lymph node metastasis and TNM stage (all P <0.05), but not with sex and age (P>0.05). The expression of galectin-3 was down-regulated significantly by siRNAGal3 (P<0.05). After interference with galectin-3, the proliferation and invasion of T24 cells was significantly decreased (all P<0.05) but the apoptosis was significantly increased (P<0.05). Conclusion: Galectin-3 is over-expressed in bladder cancer and is closely related to the clinicopathological features of bladder cancer patients. Interference of galectin-3 protein expression can inhibit proliferation and invasion and promote cell apoptosis of bladder cancer T24 cells. ··

A water-soluble two-photon ratiometric triarylboron probe with nucleolar targeting by preferential RNA binding.

By functionalizing triarylboron with cyclen, we developed a two-photon fluorescence probe, TAB-2, which can selectively bind RNA with a ratiometric readout. We tested TAB-2 in NIH/3T3 fibroblast cells, and demonstrated its capability in visualizing nucleoli and analyzing microenvironment polarity by two-photon and fluorescence-lifetime imaging microscopy.

In vitro and in vivo degradation of potential anti-adhesion materials: Electrospun membranes of poly(ester-amide) based on l-phenylalanine and p-(dioxanone).

Electrospun membranes of poly(p-dioxanone-co-l-phenylalanine) (PDPA) hold potential as an anti-adhesion material. Since adjustable degradation properties are important for anti-adhesion materials, in this study, the in vitro and in vivo degradation processes of PDPA electrospun membranes were investigated in detail. The morphological analysis of these membranes revealed the main degradation conditions of PDPA membranes. The weight remaining and molecular weight variation showed that the overall degradation rate of the membranes could be adjusted by modulating the molecular structure of the PDPAs. Especially, α-chymotrypsin could catalyze the degradation process of PDPAs. Based on these results, the in vitro degradation mechanism was demonstrated, and confirmed by 1 H NMR of the hydrolysis products. Finally, the in vivo degradation and biocompatibility of different PDPAs were investigated. The kinetic study showed that the in vitro and in vivo molecular weight loss of PDPAs have the first-order characteristics. The in vivo degradation rate of the most Phe-containing PDPA-3 is the slowest, and this result relates to the biocompatibilities of PDPAs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1369-1378, 2017.

Effects of RNAi-mediated MUC4 gene silencing on the proliferation and migration of human pancreatic carcinoma BxPC-3 cells.

It was previously demonstrated that mucin 4 (MUC4) is not expressed in normal pancreatic tissues or in chronic pancreatitis tissue but is highly expressed in pancreatic cancer (PC) tissue. Effective MUC4 gene knockdown in PC may contribute to the elucidation of pancreatic tumor development and metastasis, and may be valuable in new therapeutic approaches. Thus to confirm this, in the present study, the BxPC-3 cell line was transfected with eight pairs of shRNA lentiviral vectors for MUC4. The qPCR results showed that expression of MUC4 mRNA in the BxPC-3 cells was significantly decreased at 96 h after transfection. One of these shRNA lentiviral vectors (shRNA­A141) had showed the strongest suppressive effect on MUC4 mRNA expression and was used for MUC4 knockdown in BxPC-3 cells. After stable transfection, BxPC-3 cells showed a significantly lower expression of MUC4 mRNA and MUC4 protein, and were suppressed on cell growth and migration. In vivo, lower tumor growth rates and tumor volume were observed in the tumors derived from the MUC4-knockdown cells, whereas the transplanted tumors derived from the control group cells, grew rapidly. Thus, inhibition of MUC4 expression may be an effective means for mitigating metastasis and invasion of PC.

[PPARdelta + 294T/C gene polymorphism related to plasma lipid, obesity and left ventricular hypertrophy in subjects with metabolic syndrome].

OBJECTIVE: To investigate the relationship between PPARdelta + 294T/C gene polymorphism and lipid profile, obesity and left ventricular hypertrophy (LVH) in patients with metabolic syndrome (MS). METHODS: This study was conducted in 300 patients with MS and 174 patients with essential hypertension (EH) and 143 patients with type 2 diabetes mellitus (T2DM). MS was diagnosed according to 1999 WHO criteria. Fasting insulin (FINS), fasting blood glucose (FBG), plasma lipids levels were measured, LVH was examined by Doppler echocardiography. The PPARdelta + 294T/C gene polymorphism were analyzed using polymerase chain reaction and subsequently digested by BSLI restriction endonuclease. RESULTS: The frequencies of the PPARdelta + 294T/C genotypes were not different among three groups. Compared with T2DM and EH, MS patients had significantly higher body mass index (BMI), plasma total cholesterol, TG and LDL-C levels (P < 0.01 or P < 0.05). LVM, LVMI and incidence rate of LVH were significantly higher in MS and EH patients than that in T2DM (P < 0.01). MS patients with CC genotype had significantly higher total cholesterol and LDL-C levels than those with TT and TC genotypes (total cholesterol in CC genotype: 6.13 +/- 1.86 mmol/L vs in TC genotype: 5.14 +/- 1.10 mmol/L, P < 0.05, and CC genotype: 6.13 +/- 1.86 mmol/L vs TT genotype: 4.99 +/- 1.42 mmol/L, P < 0.01; LDL-C in CC genotype: 3.82 +/- 1.52 mmol/L vs in TC genotype: 3.14 +/- 0.88 mmol/L, P < 0.05, and in CC genotype: 3.82 +/- 1.52 mmol/L vs in TT genotype: 2.90 +/- 0.87 mmol/L, P < 0.01). BMI and LVMI in MS patients with C allele carriers (CC + TC) were significantly higher than that of TT genotype (LVMI in CC + TC: 46 +/- 10 g/m(2.7) vs in TT: 44 +/- 10 g/m(2.7); BMI in CC + TC: 26 +/- 3 kg/m(2) vs in TT: 25 +/- 3 kg/m(2), P < 0.05). CONCLUSIONS: It is indicated that PPARdelta + 294T/C gene polymorphism in subjects with MS may be involved in the occurrence of obesity and dyslipidemia. MS patients with C allele had a predominant LVH than subjects with TT genotype.

[Peroxisome proliferator-activated receptor gamma C-161T polymorphism and carotid artery atherosclerosis in metabolic syndrome].

OBJECTIVE: To assess the relationship between PPAR gamma C161-T polymorphism and Carotid Atherosclerosis in metabolic Syndrome (MS). METHODS: Polymerase chain reaction-restricted fragments length polymorphism was used to study the distribution of the PPAR gamma C161-T polymorphism in 248 metabolism syndrome, 163 essential hypertension (EH) and 115 type 2 diabetes mellitus (DM) patients and 121 normal controls. Fasting insulin (FINS), fasting blood glucose (FBG), uric Acid (UA), plasma lipids and ultrasonography for carotid artery were examined. RESULTS: Waistline and BMI were significantly higher in MS compared with those in control, EH and DM (P < 0.01). systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) were markedly higher in MS and EH compared with those in DM and control (P < 0.01). The frequencies of the CC, CT and TT were 74.6%, 21.8% and 3.6% in MS respectively, The frequencies of the CC was significantly higher in MS compared with that in control, but T allele carrier (CT + TT) was significantly lower compared with control, DM and EH (P < 0.05 or P < 0.01). In MS, CC genotype had significantly increased the intima-media thickness (IMT) of common carotid artery and plaque index compared with CT + TT (IMT: 0.84 mm +/- 0.3 mm vs 0.66 mm +/- 0.19 mm; plaque index: 2.19 +/- 1.21 vs 1.66 +/- 1.36, P < 0.05), CC genotype had significantly increased plaque index compared with CT + TT in EH and DM (plaque index: EH: 1.55 +/- 1.23 vs 1.29 +/- 0.92; DM: 1.57 +/- 1.2 vs 1.18 +/- 0.85, P < 0.05); CC genotype had significantly higher SBP compared with CT + TT in EH (P < 0.05), CC genotype had significantly increased plaque index in MS than that in DM and EH (P < 0.01), CC genotype had significantly increased IMT in MS compared with DM. CC genotype had significantly higher SBP and PP compared with CT + TT in MS (SBP: 155 mm Hg +/- 23 mm Hg vs 145 mm Hg +/- 21 mm Hg; PP: 69 mm Hg +/- 8 mm Hg vs 58 mm Hg +/- 8 mm Hg, 1 mm Hg = 0.133 kPa, P < 0.05). CONCLUSION: In MS, CC genotype was prone to lesion of carotid artery, but CT + TT may reduce lesion of carotid artery, which implicates that PPAR gamma C161-T may play a important role in carotid artery arteriosclerosis.