甘露聚糖、壳聚糖、α-酸性糖蛋白和姜黄素对脂蛋白(a)和去唾液酸脂蛋白(a)代谢影响的对比分析

分析多糖和姜黄素对脂蛋白 (a)和去唾液酸脂蛋白 (a)代谢的影响 ,从刺猬腋下静脉注入甘露聚糖、壳聚糖、α -酸性糖蛋白和姜黄素 ,2min后注射12 5I-脂蛋白 (a)或12 5I-去唾液酸脂蛋白 (a) ,1h后处死动物 ,测定血、肝、肾、脾、胆汁和肾上腺的同位素含量。结果发现 ,脂蛋白 (a)去唾液酸后能大量进入肝脏 ,加速在体内的分解代谢 ,使血中浓度迅速降低。α -酸性糖蛋白抑制组织对脂蛋白 (a)和去唾液酸脂蛋白 (a)的摄入 ,使血中脂蛋白 (a)和去唾液酸脂蛋白 (a)含量显著增高。壳聚糖和姜黄素增加肝脏和肾上腺对脂蛋白 (a)的摄取 ,使血中脂蛋白 (a)含量略降低 ,但对去唾液酸脂蛋白 (a)代谢无明显影响。甘露聚糖增加脾脏对脂蛋白 (a)的摄取 ,减少胆囊中脂蛋白 (a)含量 ,但增加肾脏和胆囊对去唾液酸脂蛋白 (a)的摄取 ,降低肾上腺对去唾液酸脂蛋白 (a)的摄取。结果提示 ,脂蛋白 (a)去唾液酸后能使脂蛋白 (a)分解代谢加快 ,脂蛋白 (a)分子中的唾液酸在结构稳定中起重要的作用。α -酸性糖蛋白抑制脂蛋白 (a)和去唾液酸脂蛋白 (a)代谢 ,而壳聚糖和姜黄素则促进脂蛋白 (a)代谢     

C3a activates the respiratory burst in human polymorphonuclear neutrophilic leukocytes via pertussis toxin-sensitive G-proteins

In contrast to C5a, which represents a well-established potent activator of the respiratory burst in polymorphonuclear neutrophilic granulocytes (PMN), the functional role of C3a in the activation of PMN is, so far, poorly understood. Herein, the potential role of human C3a in the activation of the respiratory burst in human PMN was investigated. The release of reactive oxygen species (ROS) of PMN from healthy donors was measured by lucigenin-dependent chemiluminescence. C3a dose-dependently induced the production of ROS in human PMN in the range between 10 ng/mL and 1,000 ng/mL, whereas C3a-desArg was inactive. Flow cytometric measurement of H2O2 by dihydrorhodamine-123 labeling of anti-CD16-stained PMN showed that predominantly neutrophilic PMN are responsible for the C3a-induced activation of the respiratory burst. To exclude that C3a stimulation was caused by contamination with C5a, the specificity of C3a-induced activation of PMN was shown using monoclonal antibodies (MoAbs). Accordingly, the effect of C3a was completely abolished in the presence of Fab fragments of a blocking anti-C3a MoAb. In addition, blockade of the C5a receptor by the anti-C5a receptor (anti-C5aR) MoAb, S5/1, totally inhibited the C5a-induced production of ROS, whereas the C3a response in the presence of the anti-C5aR MoAb was unaffected. The specificity of the response was further confirmed by homologous desensitization after restimulation with C3a. In contrast, no cross-desensitization was observed upon stimulation with C5a. The C3a-induced ROS production by PMN was inhibited by pertussis toxin, indicating the involvement of guanine nucleotide-binding proteins (Gi proteins) in the signal transduction process initiated by C3a. In addition, stimulation of PMN by C3a resulted in a transient increase in the cytosolic free calcium concentration ([Ca2+]i) in a dose-dependent manner. In contrast to C3a- induced ROS production, C3a did not induce a chemotactic response in PMN, indicating functional qualitative differences as compared with C5a. In summary, these results show that C3a is a potent activator of the respiratory burst in human PMN. Therefore, these findings point to a novel role of C3a in the pathogenesis of inflammatory diseases associated with increased C3a levels and PMN activation.     

Pervenous retrieval of embolized catheters from the right heart and pulmonary arteries.

Successful removal of embolized or retained catheter fragments from the right heart was achieved in two out of four patients using pervenous catheter techniques. For the first time a fragment, radiolucent on image intensification, was retrieved from the right pulmonary artery using a wire snare. In a second case a hook-loop was made in the right ventricle with a Judkins left femoral coronary angiographic catheter, which has advantages over previously described hooking devices, to withdraw a fragment to the iliac vein for subsequent snaring. Failure of retrieval occurred only in specially difficult circumstances; when a catheter embolized to the pulmonary artery of a Tetralogy of Fallot, and when in spite of successful ensnarement, a fractured electrode was firmly adherent to the right ventricular apex. Successful pervenous retrieval may require a combination of techniques which move or dislodge, such as a hook or balloon combined with those which ensnare, such as a wire loop or bioptome. Using such techniques, with minimal additions to standard equipment, retrieval procedures can be offered as a routine cardiac catheterization service with a high rate of success.     

Prediction of moderate or severe pulmonary hypertension by main pulmonary artery diameter and main pulmonary artery diameter/ascending aorta diameter in pulmonary embolism

We investigated the accuracy of computed tomographic measurements of main pulmonary artery diameter (MPAD) and of MPAD/ascending aorta diameter (AAD) in predicting moderate or severe pulmonary hypertension in 190 patients with acute pulmonary embolism. A pulmonary artery systolic pressure of > or = 50 mm Hg measured by Doppler echocardiography was considered moderate or severe pulmonary hypertension. A MPAD of > 28.6 mm and a MPAD/AAD ratio of > or = 1.00 measured by computed tomography were considered abnormal. A MPAD of > 28.6 mm had a 75% sensitivity and specificity, a 52% positive predictive value, a 89% negative predictive value, a 3.0 likelihood ratio for a positive test, and a 0.33 likelihood ratio for a negative test in predicting moderate or severe pulmonary hypertension. A MPAD/AAD ratio of > or = 1.00 had a 59% sensitivity, a 82% specificity, a 55% positive predictive value, a 84% negative predictive value, a 3.3 likelihood ratio for a positive test, and a 0.50 likelihood ratio for a negative test.     

Unidirectional rotary motion in a liquid crystalline environment: color tuning by a molecular motor

Life could not exist without motion induced by a variety of molecular motors. The construction of artificial motors by chemical synthesis, which can power motions that lead to macroscopic detectable effects in a system, is a major endeavor in contemporary science. To move toward this goal, a host-guest system, composed of a nematic liquid crystal film doped with a chiral light-driven molecular motor, is assembled. Irradiation of the film results in unidirectional rotary motion of the molecular motor, which induces a motion of the mesogenic molecules leading to a molecular reorganization and, as a consequence, a change in the color of the film. In this way, by control of the rotary motion at the molecular level, color tuning over the entire visible spectrum is achieved. These findings demonstrate that a molecular motor can exert a visually observable macroscopic change in a material.     

Zn deficiency aggravates hypertension in spontaneously hypertensive rats: possible role of Cu/Zn-superoxide dismutase

Using spontaneously hypertensive rats (SHR) fed a standard or a Zn-deficient diet for 4 weeks, we examined whether Zn deficiency affects systemic blood pressure (BP) levels in a genetically hypertensive state through a fall in the activity of Cu/Zn-superoxide dismutase (SOD). SHR fed a Zn-deficient diet had a progressive increase in systolic BP during the dietary conditioning. Consequently, SHR fed a Zn-deficient diet exhibited significantly increased levels of systolic BP by 2 weeks after the start of dietary treatment when compared with SHR fed a standard diet. Similarly, levels of basal mean arterial pressure (MAP) observed at the end of dietary treatment were SHR fed a Zn-deficient diet > SHR fed a standard diet. Administration of the nitric oxide synthase (NOS) inhibitor, L-NAME, caused an increase in MAP levels in the two groups of rats, demonstrating the involvement of the vasodilator, nitric oxide (NO), in the regulation of systemic BP in a genetically hypertensive state. The expression of endothelial (e) NOS mRNA and protein in the thoracic aorta paralleled basal MAP levels in the two groups of rats, suggesting the counter-regulation of eNOS against the developed hypertensive state in SHR fed a Zn-deficient diet. On the other hand, administration of the superoxide scavenger, tempol (a SOD mimetic compound), led to a decrease in MAP levels in the two groups of rats, indicating the participation of the oxygen free radical, superoxide, in an increase in systemic BP in a genetically hypertensive state. As reported recently, the mechanism involved is due likely to a decrease in the action of the vasodilator, NO, based on the formation of peroxynitrite coming from the non-enzymatic reaction of superoxide and NO. In addition, tempol treatment completely restored MAP levels in SHR fed a Zn-deficient diet to levels comparable to those observed in SHR fed a standard diet, indicating that a further increase in systemic BP levels seen in SHR fed a Zn-deficient vs. a standard diet is presumably brought by a reduction in the action of the vasodilator, NO, resulting from an increase in the action of superoxide. The activity of the superoxide scavenger, Cu/Zn-SOD, in the thoracic aorta was significantly decreased in SHR fed a Zn-deficient diet relative to SHR fed a standard diet. It appears that a decrease in the activity of Cu/Zn-SOD observed in the thoracic aorta of SHR fed a Zn-deficient diet at least in part plays a role in an increase in the action of superoxide in this model. Thus, Zn deficiency may be a factor to develop genetic hypertension presumably through the oxidative stress caused by superoxide.     

Early treatment during a primary malaria infection modifies the development of cross immunity

We have used a murine model to study the kinetics of cross-protection when a primary infection is halted at different times. We analysed how parasitaemia is modified during a second infection with the homologous parasite, a heterologous parasite, or a mixture of the two. In addition, possible mechanisms involved in cross-protection were analysed. Results show that treatment with pyrimethamine on day 5 during a primary infection with P. chabaudi AS (non-lethal), prevents the generation of cross-protection to a new challenge with lethal P. yoelii 17XL. In contrast, when treatment is on day 7, mice survive a P. yoelii infection. Differences between both groups suggest that in order for 'preimmune' mice to survive a lethal challenge, a predominantly TH2-type response is required, with a higher mRNA expression level of IL-4 and IL-10, and a lower mRNA expression of IFN-gamma. This work shows that an early treatment of a malaria infection produced by a non-lethal parasite drives the immune response towards a loss of cross-protection to further infections, in particular with more virulent parasites. This finding should be taken into account for the development of effective malaria vaccines.     

Hemodynamic effects of adenosine in conscious hypertensive and normotensive rats

Mean arterial pressure and heart rate were measured during intra-aortic arch (i.a.a.), intravenous, and suprarenal artery (s.r.a.) infusions of adenosine in conscious, unrestrained normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in the absence and presence of ganglionic blockade. In both groups, i.a.a. and i.v. infusions of adenosine induced comparatively larger dose-dependent reductions in mean arterial pressure than did s.r.a. infusions. In WKY, i.a.a. and i.v. infusions of adenosine were equipotent in reducing mean arterial pressure. In contrast, i.a.a. infusion of adenosine was approximately twice as potent as i.v. infusion in SHR. Also, SHR were approximately 6.5 and 2.6 times more sensitive to i.a.a. and i.v. infusions of adenosine, respectively, than were WKY. Further, i.a.a. and s.r.a. infusions of adenosine caused tachycardia in WKY, while i.v. infusions did not alter heart rate. In SHR, neither i.a.a. nor s.r.a. infusion of adenosine altered heart rate, but i.v. infusion induced a profound bradycardia. In ganglionic-blocked WKY that received a norepinephrine infusion to restore blood pressure and heart rate to pre-ganglionic blockade levels, depressor responses to i.a.a. infusion of adenosine were unchanged while the increase in heart rate was abolished. In SHR, ganglionic blockade markedly decreased the depressor response to i.a.a. and i.v. infusions of adenosine and abolished the bradycardic response to i.v. infusion. These results suggest that adenosine is an effective hypotensive agent in both WKY and SHR; however, marked between-strain differences exist in the cardiovascular response to adenosine. These differences most likely are due to changes in adenosine-pulmonary interactions and increases in the importance of adenosine-autonomic interactions in SHR.     

Diverticular fecalith in scleroderma simulating colonic neoplasm: Report of a case

This is a report of a patient with the CRST syndrome, a mild variant of scleroderma consisting of calcinosismraynaud's phenomenon, sclerodactyly, and telangiectasia. Typical changes of scleroderma were present in the extremities, esophagus, duodenum and colon. In addition, there was a polypoid filling defect in a colonic diverticulum due to a fecalith. The radiologic appearance at first resembled a colonic neoplasm, although its location within a diverticulum and its speckled appearance suggested the possibility of a fecalith. This was confirmed at colonoscopy, which disclosed numerous wide-mouthed diverticula, with inspissated fecal material projecting from several diverticula. In patients with scleroderma and polypoid filling defects in the colon, the possibility of a fecalith within a diverticulum should be considered. Where the radiologic study is inconclusive, colonoscopy may provide a definitive diagnosis.     

丙型肝炎病毒非编码区ABC程序酶切分型研究

目的为进一步了解中国是否存在HCV 3b基因及1a、2b和6a基因型感染，建立HCV 5′端非编码区(5′ NCR)不同基因型的基因库。方法分型方法按ABC程序进行，A应用BHH′(BsrBⅠ、HaeⅡ、HinfⅠ)复介内切酶消化5′NCR cDNA，可将不同基因型划分为5组：1a、1b，6a，2a、2b，3a，3b、4a。B应用BstU Ⅰ内切酶鉴别1a、1b。C应用Hae Ⅲ内切酶鉴别2a、2b、3b、4a及6a。电泳检测片段大小。结果(1)la、1b、2a、2b、3a、3b、4a、6a 8种基因型参比品的ABC分型结果表明，该8种基因型获得良好的分型效果。(2)93份HCV RNA阳性患者ABC分型结果表明，1b型感染率占66．67％，2a型18．28％，1b／2b型、3b型及2b型均为3．23％，2a／2b型和1b／2a型各为2．15％，1a型1．08％。结论结果表明应用HCV 5′-NCR ABC分型技术既保证了HCV RNA检测的灵敏度，又能完成1a-6a型中的8种基因型的鉴别。     

Corticotropin-induced reduction of plasma lipoprotein(a) concentrations in healthy individuals and hemodialysis patients: relation to apolipoprotein(a) size polymorphism

Lipoprotein(a) [Lp(a)], a strong independent cardiovascular risk factor, consists of the unique apolipoprotein(a) [apo(a)] covalently linked to a low-density lipoprotein particle. Apo(a) contains a widely differing number of the plasminogen-like kringle IV, a size polymorphism that is codominantly inherited. In addition to powerful genetic control, renal failure is known to influence the plasma Lp(a) concentration. There is still a lot to be learned about the mode and site of catabolism of Lp(a), and there is no readily applicable Lp(a)-lowering treatment available. Therefore, it was of interest to study further the Lp(a)-lowering effect of corticotropin (ACTH) that has been demonstrated in small studies. The main purpose of the present study was to investigate the influence of ACTH on different apo(a) isoforms. Short-term treatment with ACTH decreased the plasma Lp(a) concentration in all 26 study participants. The two study groups (12 healthy individuals and 14 hemodialysis patients) responded similarly, with a median decrease in plasma Lp(a) of 39% and 49%, respectively. In subjects with two clearly separable apo(a) bands, apo(a) phenotyping and densitometric scanning of the bands before and after treatment with ACTH revealed a change in the proportion of apo(a) isoforms, ie, a shift toward the isoform with lower molecular weight. This was observed in seven of nine investigated subjects (four of five healthy individuals and three of four hemodialysis patients).     

Causes of ataxia in patients attending a falls laboratory

The relationship of a range of clinical variables to balance was investigated in a group of 121 elderly patients giving a history of falls. Information collected included a clinical history and physical examination, and an evaluation of position sense, vibration sense and vestibular function. Postural changes in blood pressure were measured on a tilt-table, and sway was quantified on an ataxiameter. There was a statistically significant relationship between leg power, visual acuity, posture sense and mental function and sway, and a weaker positive association between a variety of other factors and sway. When factors showing a positive association with sway were used to construct a 'pathology' scene for each patient, it emerged that there was a statistically significant correlation between scores and ataxiameter readings. This suggests that, in the elderly, ataxia is usually the result of multiple factors.     

Clinical evaluation of different fluid-filled systems for oesophageal manometry.

In a clinical study of oesophageal manometry with fluid-filled catheters, both a non-perfused system and a perfused system with a syringe pump have been compared to a system with a low-compliance perfusion pump, which served as a reference. Significantly lower values of motility amplitudes, motility derivatives, and partly of LES pressures, and a time delay of up to 0.5 sec of the amplitude maximum were obtained with the non-perfused system and the system with a syringe pump in comparison to the low-compliance system. Since the oesophageal function can be erroneously evaluated by use of a non-perfused system or a perfused system with a syringe pump, such systems cannot be recommended for clinical use.     

Lipoprotein(a) as a Potential Causal Genetic Risk Factor of Cardiovascular Disease: A Rationale for Increased Efforts to Understand its Pathophysiology and Develop Targeted Therapies

Recent published studies have provided increasing evidence that lipoprotein(a) [Lp(a)] may be a potential causal, genetic, independent risk factor for cardiovascular disease (CVD). Lp(a) levels >25 mg/dl are present in ～30% of Caucasians and 60% to 70% of Blacks. Lp(a) is composed of apolipoprotein B-100 and apolipoprotein (a) [(apo(a)]. Circulating Lp(a) levels are primarily influenced by the LPA gene without significant dietary or environmental effects, mediating CVD risk throughout the patient's lifetime. Recent clinical outcomes studies, meta-analyses, and Mendelian randomization studies, in which randomization of Lp(a) levels is achieved through the random assortment of LPA gene variants thereby removing confounders, have shown that genetically determined Lp(a) levels are continuously and linearly related to risk of CVD. Currently, Lp(a) pathophysiology is not fully understood, and specifically targeted therapies to lower Lp(a) are not available. We provide a rationale for increased basic and clinical investigational efforts to further understand Lp(a) pathophysiology and assess whether reducing Lp(a) levels minimizes CVD risk. First, a detailed understanding of Lp(a) synthesis and clearance has not been realized. Second, several mechanisms of atherogenicity are known to varying extent, but the relative contributions of each are not known. Lp(a) may be atherothrombotic through its low-density lipoprotein moiety, but also through apo(a), including its ability to be retained in the vessel wall and mediate pro-inflammatory and proapoptotic effects including those potentiated by its content of oxidized phospholipids, and antifibrinolytic effects. Finally, development of specific Lp(a)-lowering agents to potently lower Lp(a) will allow testing of mechanistic hypotheses in animal models and the design of randomized clinical trials to assess reduction in CVD. A convergence of academic, scientific, pharmaceutical, and National Institutes of Health priorities and efforts can make this a reality in the next decade.     

The rehabilitation of clinical assessment for the diagnosis of pulmonary embolism

Pulmonary angiography is the gold standard for diagnosis of segmental pulmonary embolism, but no longer for subsegmental pulmonary embolism because the inter-observer agreement for angiographically documented subsegmental pulmonary embolism is only 60%. A normal rapid ELISA VIDAS D-dimer test result and a normal perfusion scan exclude pulmonary embolism with a negative predictive value of >99%, irrespective of clinical score. The positive predictive value for pulmonary embolism of a high probability VP-scan compared to pulmonary angiography is 87% indicating that 13% of patients with a high probability VP-scan do not have pulmonary embolism. The combination of a negative CUS, a low clinical score, and a non-diagnostic VP-scan safely excludes pulmonary embolism. Patients with a non-diagnostic VP-scan, a negative CUS, but a moderate to high clinical score are candidates for pulmonary angiography. The positive predictive value of helical spiral CT is >95 to 99%. The combination of a negative CUS, a low clinical score, and the presence of a clear alternative diagnosis is predicted to safely exclude pulmonary embolism. Helical spiral CT detects all clinical relevant pulmonary emboli and a large number of alternative diagnoses in symptomatic patients with a non-diagnostic or a high-probability VP-scan. The negative predictive value during 3 months followup after a negative spiral CT for pulmonary embolism in 4 retrospective studies and 1 prospective management study was >99%. Only a small group of patients (1-2%) with a non-diagnostic spiral CT are candidates for pulmonary angiography. Therefore, it is predicted that the spiral CT will replace both VP-scanning and pulmonary angiography to safely exclude or diagnose pulmonary emboli in patients with suspected pulmonary embolism.     

Rectal injury caused by a personal watercraft accident

PURPOSE: An original case of rectal injury after a personal watercraft accident is reported. Principles of rectal trauma management are discussed. METHODS: We present a case of a rectal injury after a fall from a personal watercraft. Rigid sigmoidoscopy and a water-soluble contrast enema documented a posterior rectal tear. The patient was managed by diversion, drainage, and administration of antibiotics. RESULTS: The patient's rectal tear healed without complication. CONCLUSION: To our knowledge, this is the first reported case of an injury to the rectum as a result of a personal watercraft accident. A high suspicion of rectal injury must be maintained in victims who have fallen from the back of a personal watercraft. Treatment of a rectal injury should follow the basic principles of drainage, diversion, and administration of antibiotics, but variations in traditional management may be appropriate. Finally, preventative methods including wearing protective clothing, and possible modification to the watercraft to reduce risk of injury should be considered.     

Clinicopathologic characteristics and prognoses of gastric cancer in patients with a positive familial history of cancer

BACKGROUND: There is a significant association between a positive family history of cancer and gastric cancer risk; however, the clinicopathologic characteristics and prognoses of gastric cancer patients with a positive family history of cancer are not clear. GOALS: To define the clinicopathologic characteristics and prognoses of gastric cancer patients with a positive family history of cancer. STUDY: We reviewed 548 patients with pathologically confirmed primary gastric cancer who had undergone a gastrectomy between 1990 and 1996. The average age was 59.7 years, and the male-to-female ratio was 1.7. The familial cancer histories of these patients were reviewed, and the various clinicopathologic characteristics of those patients with a positive family history of cancer were compared with those with a negative history. RESULTS: Among this cohort, 74 (13.5%) patients had a positive family history of cancer in their primary or secondary relatives. The most common cancer was gastric cancer in 29 patients, followed by colorectal cancer in 10 and lung cancer in 7. Patients with a positive family history of cancer were associated with bigger tumors, and more patients received a total gastrectomy than did patients with a negative family history. Immunopathologic study disclosed a higher rate of p53 overexpression but not of neu or c-met in patients with a positive family history of cancer. There were no differences in the mean age, gender, site, depth of invasion, or TNM stage. The survival curve of patients with a positive family history of malignancy was similar to that of patients without a family cancer history. CONCLUSION: Patients with gastric cancer with a positive family history of cancer appeared to have bigger tumors with a higher rate of p53 overexpression, and more patients required a total gastrectomy compared with those with a negative family history. This study suggests a genetic component in the aggressiveness of gastric cancer and indicates that higher caution should be exercised with people who have a positive family history of cancer.     

Space-occupying lesion of the pancreas--how frequently not due to a suspected ductal adenocarcinoma?

In patients with a space-occupying lesion of the pancreas at first a primary ductal adenocarcinoma is considered as the cause. Other tumours or metastases are assumed to occur very rarely. Therapy and prognosis of other pancreas tumours differ from therapy and prognosis of a primary ductal adenocarcinoma. We therefore examined the question of how frequently a space-occupying lesion of the pancreas was not due to a ductal adenocarcinoma in our case materials. Retrospectively 70 patients who had undergone a percutaneous puncture of a space-occupying mass of the pancreas under ultrasonographic control were included in the study (34 women, 36 men). In 62 patients a clear histological diagnosis was possible on the basis of the biopsy. In 53 cases (76 %) a primary adenocarcinoma of the pancreas could be diagnosed. In 5 patients (7 %) these masses turned out to be metastases of a previously known malignant tumour disease (2 x mammary carcinoma, 2 x gastric carcinoma, 1 x sigmoid carcinoma). Other tumours could be detected in 4 cases (6 %) including a tuberculoma, an endocrine tumour, a fusocellular sarcoma with partial neurogenic differentiation and a large-cell and pleomorphic-cell anaplastic, partly sarcomatoid carcinoma. In patients with a space-occupying lesion of the pancreas, tumours other than a ductal adenocarcinoma are not rare. In particular, in cases of a previously known malignant tumour disease a space-occupying lesion of the pancreas can also turn out to be a metastasis. Every other individual tumour entity is rare. Other tumour entities at large, however, are found in daily routine. The preoperative biopsy of space-occupying lesions of the pancreas, therefore, still has a clinical importance for the further therapy planning.     

Mitogenic activity of oxidized lipoprotein (a) on human vascular smooth muscle cells

Although oxidized lipoproteins may play an important role in the progression of atherosclerosis, no report has mentioned the significance of oxidized lipoprotein (a) (Lp[a]) in the pathogenesis of cardiovascular disease. Initially, we compared the mitogenic actions of Lp(a) and oxidized Lp(a) on human vascular smooth muscle cells (VSMC). Lp(a) significantly stimulated the growth of human VSMC in a dose-dependent manner, whereas oxidized Lp(a) showed a stronger stimulatory action on VSMC growth than native Lp(a). Interestingly, antioxidants probucol and fluvastatin inhibited the oxidation of Lp(a). Moreover, the stimulatory effect of oxidized Lp(a) on human VSMC growth was significantly inhibited by probucol. Finally, we elucidated the molecular mechanisms of how Lp(a) stimulated the growth of VSMC. Extracellular signal-regulated kinase (ERK), as those controlled by kinases, modulate critical cellular functions such as cell growth, differentiation, and apoptosis, was transiently phosphorylated by oxidized Lp(a) as well as native Lp(a) from 5 minutes, and the phosphorylation disappeared within 30 minutes. The degree of ERK phosphorylation by oxidized Lp(a) was much higher than that by native Lp(a). Administration of a specific inhibitor of MEK, PD 98059, significantly attenuated VSMC growth induced by native Lp(a) or oxidized Lp(a) in a dose-dependent manner (P<0.01). The current study demonstrated that oxidized Lp(a) is more potent than native Lp(a) in stimulating VSMC growth. Oxidized Lp(a) may play an important role in the pathogenesis of vascular disease.