Biomedical subjects

Jian Liu

Publications and source records attributed to Jian Liu.

At least 73 records · Page 4Linked to original sources

PubMed2005

Inhibition or activation of Apert syndrome FGFR2 (S252W) signaling by specific glycosaminoglycans.

Most Apert syndrome patients harbor a single amino acid mutation (S252W) in fibroblast growth factor (FGF) receptor 2 (FGFR2), which leads to abnormal FGF/FGFR2 signaling. Here we show that specific combinations of FGFs and glycosaminoglycans activate both alternative splice forms of the mutant but not of the wild-type FGF receptors. More importantly, 2-O- and N-sulfated heparan sulfate, prepared by a combined chemical and enzymatic synthesis, antagonized the over-activated FGFR2b (S252W) to basal levels at nanomolar concentrations. These studies demonstrated that specific glycosaminoglycans could be useful in treating ligand-dependent FGFR signaling-related diseases, such as Apert syndrome and cancer.

Acrocephalosyndactylia↗

PubMed2005

Characterization of the N-deacetylase domain from the heparan sulfate N-deacetylase/N-sulfotransferase 2.

Heparin and heparan sulfate are linear sulfated polysaccharides that exert a multitude of biological functions. Heparan sulfate glucosaminyl N-deacetylase/N-sulfotransferase isoform 2 (NDST-2), a key enzyme in the biosynthesis of heparin, contains two distinct activities. This bifunctional enzyme removes the acetyl group from N-acetylated glucosamine (N-deacetylase activity) and transfers a sulfuryl group to the unsubstituted amino position (N-sulfotransferase activity). The N-sulfotransferase activity of NDST has been unambiguously localized to the C-terminal domain of NDST. Here, we report that the N-terminal domain of NDST-2 retains N-deacetylase activity. The N-terminal domain (A66-P604) of human NDST-2, designated as N-deacetylase (NDase), was cloned as a (His)(6)-fusion protein, and protein expression was carried out in Escherichia coli. Heparosan treated with NDase contains N-unsubstituted glucosamine and is highly susceptible to N-sulfation by N-sulfotransferase. Our results conclude that the N-terminal domain of NDST-2 contains functional N-deacetylase activity. This finding helps further elucidate the mechanism of action of heparan sulfate N-deacetylase/N-sulfotransferases and the biosynthesis of heparan sulfate in general.

Binding Sites↗

PubMed2005

Single-step syntheses of 2-amino-7-chlorothiazolo[5,4-d]pyrimidines: intermediates for bivalent thiazolopyrimidines.

[reaction: see text] A single-step process for the preparation of 2-amino-7-chlorothiazolo[5,4-d]pyrimidines, 2, was achieved by the reaction of the commercially available 4,6-dichloro-5-aminopyrimidine 1 with isothiocyanates. This mild reaction accommodates a variety of functionalized isothiocyanates and proceeds in good to excellent yields. The utility of such intermediates is exemplified by subsequent reaction with alkyl or arylamine nucleophiles to afford novel, differentially functionalized 2,7-diaminothiazolo[5,4-d]pyrimidines, 3.

Molecular Structure↗

PubMed2005

Enzymatic synthesis of heparin related polysaccharides on sensor chips: rapid screening of heparin-protein interactions.

The biological roles of heparin (HP) and heparan sulfate (HS) are mediated mainly through their interaction with proteins. In the present work, we provide a rapid method for screening HP/HS-protein interactions providing structural data on the key sulfo groups that participate in the binding. A library of polysaccharides structurally related to HP was prepared by immobilizing the biotinylated N-sulfated K5 polysaccharide (N-sulfoheparosan) on sensor chips followed by selective modification of this polysaccharide with enzymes that participate in HP/HS biosynthesis. The polysaccharides synthesized on the surface of the sensor chips differ in the number and position of sulfo groups present both on uronic acid and glucosamine residues. Surface plasmon resonance was used to measure the interaction of each member of this polysaccharide library with antithrombin III (ATIII), to afford structural information on sulfo groups required for this HP/HS-protein interaction. This method is viewed as widely applicable for the study of the structure-activity relationship (SAR) of HP/HS-protein interactions.

Antithrombin III↗

PubMed2005

Birth order and sexual orientation in men: evidence for two independent interactions.

Birth order is correlated with male sexual orientation, but the reason(s) for this relationship is unclear. In the present study, data from a Canadian sample of homosexual and heterosexual men (N=604) were used to present evidence of two independent birth order interactions--one with height and the other with parental age--predicting sexual orientation in men. If these findings prove reliable, it raises the possibility that different aetiological factors underlie the birth order/sexual orientation relationship in men.

Adolescent↗

PubMed2005

Enzymatic redesigning of biologically active heparan sulfate.

Heparan sulfate carries a wide range of biological activities, regulating blood coagulation, cell differentiation, and inflammatory responses. The sulfation patterns of the polysaccharide are essential for the biological activities. In this study, we report an enzymatic method for the sulfation of multimilligram amounts of heparan sulfate with specific functions using immobilized sulfotransferases combined with a 3'-phosphoadenosine 5'-phosphosulfate regeneration system. By selecting appropriate enzymatic modification steps, an inactive precursor has been converted to the heparan sulfate having three distinct biological activities, associated with binding to antithrombin, fibroblast growth factor-2, and herpes simplex virus envelope glycoprotein D. Because the recombinant sulfotransferases are expressed in bacteria, and the method uses a low cost sulfo donor, it can be readily utilized to synthesize large quantities of anticoagulant heparin drug or other biologically active heparan sulfates.

Animals↗

PubMed2005

Phase segregation on different length scales in a model cell membrane system.

Lipid rafts are sphingolipid- and cholesterol-enriched domains on cell membranes that have been implicated in many biological functions, especially in T lymphocytes. We used a field theory to examine the forces underlying raft formation on resting living cell membranes. We find that it is difficult to reconcile the observed size of rafts on living cell membranes ( approximately 100 nm) with a mechanism that involves coupling between spontaneous curvature differences and concentration fluctuations. Such a mechanism seems to predict raft domain sizes that are larger and commensurate with those observed on synthetic membranes. Therefore, using a Poisson-Boltzmann approach, we explore whether electrostatic forces originating from transmembrane proteins and net negative charges on cell membranes could play a role in determining the raft size in living cell membranes. We find that a balance among the intrinsic tendency of raft components to segregate, the line tension, and the effective dipolar interactions among membrane constituents leads to a stable phase with a characteristic length scale commensurate with the observed size of rafts on living cell membranes. We calculate the phase diagram of a system in which these three types of forces are important. In a certain region of the parameter space, an interesting phase with mosaic-like morphology consisting of an intertwined pattern of raft and nonraft domains is predicted. Experiments that could further assess the importance of dipolar interactions for lateral organization of the components on multiple length scales in membranes are suggested.

Algorithms↗

PubMed2005

High-performance liquid chromatography-mass spectrometric analysis of ramipril and its active metabolite ramiprilat in human serum: application to a pharmacokinetic study in the Chinese volunteers.

This study presents a rapid, specific and sensitive LC-MS/MS assay for the determination of ramipril and ramiprilat in human serum using enalapril as an internal standard (IS). A Waters Atlantis C18 column (2.1 mm x 100 mm, 3 microm) and a mobile phase consisting of 0.1% formic acid-methanol (25:75, v/v) were used for separation. The analysis was performed by the selected reaction monitoring (SRM) method, and the peak areas of the m/z 417.3-->234.3 and m/z 389.3-->206.2 transition for ramipril and ramiprilat, respectively, were measured versus that of the m/z 377.3-->234.2 for IS to generate the standard curves. The assay linearities of ramipril and ramiprilat were confirmed over the range 0.10-100 ngml(-1) and 0.25-100 ngml(-1), respectively, and limits of quantitation for them were 0.10 and 0.25 ngml(-1), respectively. The linear ranges correspond well with the serum concentrations of the analytes obtained in clinical pharmacokinetic studies. Intraday and interday relative standard deviations of ramipril and ramiprilat were 2.8-6.4% and 4.3-4.6%, 4.4-6.7% and 3.5-4.7%, respectively. The recoveries of ramipril and ramiprilat from serum were in the range of 81.0-98.2%. The developed LC-MS procedures were applied for the determination of the pharmacokinetic parameters of ramipril and ramiprilat following a single oral administration of 10mg ramipril tablets in 18 Chinese healthy male volunteers.

Administration, Oral↗

PubMed2005

Niemann-Pick C1 protein facilitates the efflux of the anticancer drug daunorubicin from cells according to a novel vesicle-mediated pathway.

Niemann-Pick C1 (NPC1) is a late endosomal/lysosomal membrane protein originally reported on for its role in cholesterol trafficking in mammalian cells. NPC1 has been shown recently to share significant structural homology with a family of prokaryotic permeases and was proposed to play a role in intracellular drug transport; however, the mechanism for this has not been fully understood. We provide evidence here that is consistent with NPC1's involvement in a vesicle-mediated clearance of the anticancer agent daunorubicin from cells. In experiments with human fibroblasts, we demonstrate that lysosomal efflux of daunorubicin, as well as dextran molecules, are significantly reduced in cells with mutated and dysfunctional NPC1 compared with wild-type fibroblasts. Furthermore, we show that NPC1 is implicated in a lysosomal drug sequestration phenotype exhibited by the multidrug-resistant (MDR) human leukemic HL-60 cancer cell line. Evaluations of cholesterol trafficking, NPC1 mRNA levels, and protein expression are all consistent with a loss of NPC1 activity that is associated with the emergence of the MDR phenotype in this cell line. Collectively, this work proposes a novel role for NPC1 in a vesicle-mediated pathway responsible for the clearance of drugs from cells and provides an explanation for a drug sequestration phenotype exhibited by the MDR HL-60 cell line.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Characterization of the structure of antithrombin-binding heparan sulfate generated by heparan sulfate 3-O-sulfotransferase 5.

The 3-O-sulfation of glucosamine is a key modification step during the biosynthesis of anticoagulant heparan sulfate (HS). Both heparan sulfate 3-O-sulfotransferase -1 (3-OST-1) and 3-O-sulfotransferase-5 (3-OST-5) transfer sulfate to the 3-OH group of glucosamine to generate antithrombin-binding heparan sulfate (HS(act)). Here, we reported the isolation and characterization of the antithrombin-binding HS oligosaccharides generated by 3-OST-5 (3-OST-5 oligo(act)). (3)H-labeled HS of Chinese hamster ovary cells was exhaustively modified by 3-OST-1 to remove the 3-OST-1 modification sites followed by antithrombin-affinity fractionation. The non-antithrombin-binding fraction of 3-OST-1 pretreated HS was further modified by 3-OST-5 to generate additional antithrombin-binding HS, which was designated as 3-OST-5 HS(act). Structural analysis of 3-OST-5 HS(act) revealed that the antithrombin-binding site of 3-OST-5 HS(act) is located within a domain clustered with N-sulfated glucosamine units. We also isolated 3-OST-5 antithrombin-binding oligosaccharides (3-OST-5 oligo(act)) from high pH nitrous acid degraded 3-OST-5 HS(act). A disaccharide analysis revealed that 3-OST-5 oligo(act) were composed of multiple 3-O-sulfated glucosamine units. Our results provide additional insights on the relationship between the anticoagulant activity and structure of HS.

Animals↗

PubMed2005

Increased serum cathepsin S in patients with atherosclerosis and diabetes.

Atherosclerosis and diabetes are closely associated and both involve extensive degradation of the aortic elastin. Increased elastase activity has been detected in diabetic animal aortae. We have demonstrated enhanced elastolytic cathepsin S in human atherosclerotic lesions but insufficient amounts of its endogenous inhibitor cystatin C, suggesting alterations of serum cathepsin S and/or cystatin C in patients with atherosclerosis or diabetes. In this study, we measured levels of both cathepsin S and cystatin C in sera from 240 patients by ELISA. Among these patients, 107 had a diagnosis of atherosclerotic stenosis, 103 were diabetic, and 30 had neither condition. Multiple linear regression analysis demonstrated that significantly higher serum levels of cathepsin S in patients with either atherosclerotic stenosis (p<0.04) or diabetes (p=0.0005) persisted after adjustment for cystatin C level, renal function, smoking, and serum glucose levels (p=0.008, p=0.0005). Furthermore, patients with acute (p=0.009) or previous myocardial infarction (p<0.02) or unstable angina pectoris (p<0.05) had elevated levels of cathepsin S after adjustment for smoking, creatinine, cystatin C, and serum glucose. In contrast, serum cystatin C levels were higher in diabetic patients (p=0.00001), but not in atherosclerotic subjects (p=0.14), than in the non-involved population after adjustment for age, smoking, and renal function. Although the pathophysiology of cathepsin S or cystatin C in atherosclerosis and diabetes requires further investigation, increased serum cathepsin S may serve as a biomarker for both diseases.

Aged↗

PubMed2005

Context- and cue-conditioned potentiation of acute morphine dependence and withdrawal.

Single morphine injections induce a state of acute opioid dependence measured by an increase in naloxone potency to precipitate withdrawal. Repeated morphine exposure (daily/weekly intervals) results in further potentiation of naloxone potency, perhaps due to conditioning mechanisms. The current study tested the hypothesis that previously neutral stimuli could elicit a conditioned potentiation of the withdrawal response following acute bolus injections of morphine. Rats trained on an FR-15 schedule for food received five morphine injections (5.6 mg/kg) at daily intervals. Four hr after morphine injection on Conditioning Days (first 4 days), naloxone (1 mg/kg)-induced suppression of responding was paired either with operant context only, or with a tone/light conditioned stimulus (CS). On Test Day low dose naloxone (0.001-0.33 mg/kg) given 4-h post-morphine preceded the operant session. Rats exposed to naloxone repeatedly in the operant context without CS (Paired-Context Only) showed an increase in naloxone potency on Test Day relative to Unpaired Controls that received all morphine and naloxone in the home cage at a different time of day than operant testing. Rats exposed to the tone/light CS on Conditioning Days also showed a significant increase in naloxone potency relative to Unpaired Controls when the CS was represented on Test Day (Paired-CS), but not when the CS was omitted on the Test Day (Paired-CS/Test Context). Thus, conditioning processes appear to play a significant role in the early development of opioid dependence and withdrawal.

Animals↗

PubMed2005

Comparison of 3D joint moments using local and global inverse dynamics approaches among three different age groups.

A complete understanding of joint moment is important to locomotion research. The purpose of the study was to compare stance phase lower extremity joint moments, calculated by a three-dimensional (3D) inverse dynamics model and expressed in global and local coordinate systems, to examine the influence of different coordinate systems on joint moment profiles. Additionally, aging influences on joint moments were examined. Thirty healthy (10 young, 10 middle-aged and 10 old) participants were involved in the current study. Kinematic and kinetic data were collected using standard gait study protocol. Results suggested that globally expressed joint moments were significantly different than those expressed locally. Furthermore, significant moment differences were found between young and old age groups. The older adults produced less evertor muscle moments at the ankle joint. However, aging effect was not significant for majority of the joint moment comparisons. It is concluded that coordinate system need to be carefully chosen, and specified in 3D joint moment analysis, while significant error introduced by using 2D analysis need to be considered.

Adult↗

PubMed2005

Application of serum protein fingerprinting coupled with artificial neural network model in diagnosis of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma tends to present at a late clinical stage with poor prognosis. Therefore, it is urgent to explore and develop a simple, rapid diagnostic method, which has high sensitivity and specificity for hepatocellular carcinoma at an early stage. In this study, the serum proteins in patients with hepatocellular carcinoma or liver cirrhosis and in normal controls were analysed. Surface enhanced laser desorption/ionization time-of-flight mass (SELDI-TOF-MS) spectrometry was used to fingerprint serum protein using the protein chip technique and explore the value of the fingerprint, coupled with artificial neural network, to diagnose hepatocellular carcinoma. METHODS: Of the 106 serum samples obtained, 52 were from patients with hepatocellular carcinoma, 22 from patients with liver cirrhosis and 32 from healthy volunteers. The samples were randomly assigned into a training group (n = 70, 35 patients with hepatocellular carcinoma, 14 with liver cirrhosis, and 21 normal controls) and a testing group (n = 36, 17 patients with hepatocellular carcinoma, 8 with liver cirrhosis, and 11 normal controls). An artificial neural network was trained on data from 70 individuals in the training group to develop an artificial neural network diagnostic model and this model was tested. The 36 sera in the testing group were analysed with blind prediction by using the same flowchart and procedure of data collection. The 36 serum protein spectra were clustered with the preset clustering method and the same mass/charge (M/Z) peak values as those in the training group. Matrix transfer was performed after data were output. Then the data were input into the previously built artificial neural network model to get the prediction value. The M/Z peaks of the samples with more than 2000 M/Z were normalized with biomarker wizard of ProteinChip Software version 3.1 for noise filtering. The first threshold for noise filtering was set at 5, and the second was set at 2. The 10% was the minimum threshold for clustering. The statistical analysis of the data of serum protein mass spectrum was performed in the groups (normal vs. hepatocellular carcinoma, and liver cirrhosis vs. hepatocellular carcinoma) with the t test. RESULTS: Comparison between the groups of hepatocellular carcinoma and normal control: The mass spectra from 56 samples (hepatocellular carcinoma and normal controls) in the training group were analysed and 241 peaks were obtained. In addition, 21 peaks from them were used for comparison between the groups of hepatocellular carcinoma and normal controls (P < 0.01). Only 2 peaks at 3015 M/Z and 5900 M/Z were selected with significant difference (P < 10 (-9)). A model was developed based on these two proteins with different M/Z. It was confirmed that this artificial neural network model can be used for comparison between the groups of hepatocellular carcinoma and normal controls. The sensitivity was 100% (17/17), and the specificity was 100% (11/11). Comparison between the groups of hepatocellular carcinoma and liver cirrhosis: The mass spectra from 49 samples in the training group (including patients with hepatocellular carcinoma and liver cirrhosis) were analysed and 208 peaks were obtained. In addition, 21 peaks from them were used for comparison between the groups of hepatocellular carcinoma and liver cirrhosis (P < 0.01). Only 2 peaks at 7759 M/Z, 13134 M/Z were selected with significant difference (P < 10 (-9)). A model was developed based on these two proteins with different M/Z. It was confirmed that this artificial neural network model can be used for comparison between the groups of hepatocellular carcinoma and liver cirrhosis. The sensitivity was 88.2% (15/17), and the specificity was 100% (8/8). CONCLUSIONS: The specific biomarkers selected with the SELDI technology could be used for early diagnosis of hepatocellular carcinoma.

Adult↗

PubMed2005

Design and characterization of a versatile reference instrument for rapid, reproducible specular gloss measurements.

A reference goniospectrophotometer has been developed at the National Research Council of Canada (NRC) for providing high-accuracy traceable measurements of specular gloss at several standard geometries, including 75 degrees for paper samples, haze and absence-of-bloom gloss, and color appearance of gonio-apparent materials. This is to the authors' knowledge the first reported reference instrument that has this level of versatility for rapidly characterizing the total visual appearance properties of a wide variety of materials and applications. This instrument also replaces the NRC glossmeter that has been providing primary level specular gloss measurements in accordance with International Organization for Standardization and American Society for Testing and Materials standards for measurements of paint and ceramic materials at geometries of 20 degrees, 60 degrees, and 85 degrees. The new instrument has been fully characterized for sources of error and compared with the NRC glossmeter. Its measurement reproducibility of 0.02 gloss unit is a factor-of-5 improvement, and its overall estimated expanded (k = 2) uncertainty is 0.3 gloss unit at all three standard geometries.

Journal Article↗

PubMed2005

[Prevention and treatment of hepatitis B virus reinfection after liver transplantation].

OBJECTIVE: To study the efficacy of the protocol of combination of lamivudine with low dosage hepatitis B immuno-globulin (HBIG) to prevent HBV reinfection and of the treatment for HBV reinfection after liver transplantation. METHODS: From December 2000 to May 2003, 11 patients (follow-up is more than 1 year) had been transplanted due to HBV related end-stage liver disease or hepatocellular carcinoma. All patients received the protocol of combination of lamivudine with low dosage HBIG to prevent HBV reinfection after liver transplantation. Lamivudine was administered for more than 2 weeks. Preoperatively patients with HBV-DNA(-) and HBeAg(-) accepted HBIG 2000 IU intramuscular injection. Patients with HBV-DNA(+) or HBeAg(+) before operation accepted HBIG 4000 IU intramuscular injection, and patients with both HBV-DNA(+) and HBeAg(+) before operation accepted HBIG 6000 IU intramuscular injection. All patients took long-term lamivudine postoperatively. They accepted HBIG 800 IU/d for 1 week after transplantation. Two weeks after operation, dosage of HBIG was adjusted so that the titer of HBsAb was higher than 500 IU/L, but lower than 1000 IU/L, and this treatment lasted for 6 months. 6 months after operation, dosage of HBIG was adjusted so that tite of HBsAb higher than 300 IU/L but lower than 500 IU/L, and this treatment lasted for 6 months. One year after operation, dosage of HBIG was adjusted so that tite of HBsAb was higher than 100 IU/L but lower than 300 IU/L, and this treatment lasted for a long time. Examinations of liver function, HBV-DNA and hepatitis B were regularly taken. To observe the early turning to be negative rate, the later HBV reinfection rate, and the efficacy of the treatment for HBV reinfection. RESULTS: HBsAg, HBeAg and HBV-DNA in all patients turned to be negative in 1-4 days after operation. All patients responded to HBIG, and level of titer of HBsAb was elevated gradually. All patients was alive during the observation time. The regular examination of HBsAb showed that of HBsAb was in line with our expectation. Hepatitis B recurrence occurred in 1 patient 25 months after transplantation. Through using adefovir and adding the dosage of HBIG, the hepatitis B is in control. CONCLUSIONS: The protocol of combination of lamivudine with low dosage HBIG proved to be highly effective and safe in preventing the recurrence of HBV after liver transplantation. It also reduced the cost obviously.

Administration, Oral↗

PubMed2005

Structural relation properties of hydrothermally stable functionalized mesoporous organosilicas and catalysis.

The surfactant assistant syntheses of sulfonic acid functionalized periodic mesoporous organosilicas with large pores are reported. A one-step condensation of tetramethoxysilane (TMOS) with 1,2-bis(trimethoxysilyl)ethane (BTME) and 3-mercaptopropyltrimethoxysilane (MPTMS) in highly acidic medium was performed in the presence of triblock copolymer Pluronic P123 and inorganic salt as additive. During the condensation process, thiol (-SH) group was in situ oxidized to sulfonic acid (-SO(3)H) by hydrogen peroxide (30 wt % H(2)O(2)). X-ray diffraction studies along with nitrogen and water sorption analyses reveal the formation of stable, highly hydrophobic, and well-ordered hexagonal mesoscopic structures in a wide range of -CH(2)CH(2)- concentrations in the mesoporous framework. The resultant materials were also investigated by (29)Si MAS and (13)C CP MAS NMR, thermogravimetric analyses, UV-Raman spectroscopy, and FT-IR spectroscopy. The role of the bridged organic group on the hydrothermal stability of the mesoporous materials was established, which revealed an enhancement in hydrothermal stability of the materials with incorporation of the bridged organic groups in the network. The catalytic performance of -SO(3)H functionalized mesoporous materials was investigated in the esterification of ethanol with acetic acid, and the results demonstrate that the ethane groups incorporated in the mesoporous framework have a positive influence on the catalytic behavior of the materials.

Journal Article↗

PubMed2005

Cathepsin L expression and regulation in human abdominal aortic aneurysm, atherosclerosis, and vascular cells.

The cysteine protease cathepsin L is one of the most potent mammalian elastases and collagenases, widely expressed at basal levels in most tested tissues and cell types, and regulated by pro-inflammatory stimuli. The inflammatory arterial diseases abdominal aortic aneurysm (AAA) and atherosclerosis involve extensive vascular remodeling that requires elastolysis and collagenolysis. This study examined the hypothesis that cathepsin L is over-expressed in human AAA and atherosclerotic lesions and its expression in vascular cell types found in these lesions is regulated by pro-inflammatory cytokines. Immunohistochemical and tissue extract immunoblot analysis demonstrated increased expression of cathepsin L in human AAA and atheromata and localized its expression to lesional smooth muscle cells (SMC), endothelial cells (EC), and macrophages. In primary cultured human SMC, EC, and monocyte-derived macrophages, pro-inflammatory cytokines or growth factors induced the expression of cathepsin L and its activity against extracellular collagen and elastin. Patients with coronary artery stenosis (n=65) had higher serum cathepsin L levels than those without lesions detectable by quantitative coronary angiography (n=30) (1.47+/-0.33 ng/ml versus 0.60+/-0.06 ng/ml, p<0.02). A strong correlation between the percent of stenosis of left anterior descending coronary artery and serum cathepsin L levels in patients with stenosis (R=0.542, p<0.0001), also suggests involvement of cathepsin L in these vascular diseases.

Animals↗