Artificial neuronal network analysis in investigating the relationship between oxidative stress and endoplasmic reticulum stress to address blocked vessels in cardiovascular disease.

Background: Cardiovascular disease is the leading cause of death in the world and is associated with significant morbidity. Atherosclerosis is the main cause of cardiovascular disease (CVD), including myocardial infarction (MI), heart failure, and stroke. The mechanism of atherosclerosis has not been well investigated in different aspects, such as the relationship between oxidative stress and endothelial function. This project aims to investigate whether an oxidative enzyme vascular peroxidase 1 (VPO1) and activating transcription factor 4 (ATF4) can be used as biomarkers in highlighting the pathogenesis of the disease and in evaluating the prognosis of the relationship with endoplasmic reticulum and oxidative stress. This paper used artificial neural network analysis to predict cardiovascular disease risk based on new generation biochemical markers that combine vascular inflammation, oxidative and endoplasmic reticulum stress. Methods: For this purpose, 80 patients were evaluated according to the coronary angiography results. hs-CRP, lipid parameters and demographic characteristics, VPO1, ATF4 and Glutathione peroxidase 1(GPx1) levels were measured. Results: We found an increase in VPO1 and hs-CRP levels in single-vessel disease as compared to controls. On the contrary, ATF4 and GPx1 levels were decreased in the same group, which was not significant. Our results showed a significant positive correlation between ATF4 and lipid parameters. A statistically significant positive correlation was also observed for VPO1 and ATF4 (r=0.367, P<0.05), and a negative correlation was found for ATF4 and GPx1 (r=-0.467, P<0.01). A significant negative relationship was noted for GPx1 and hs-CRP in two/three-vessel disease (r=-0.366, P<0.05). Artificial neural network analysis stated that body mass index (BMI) and smoking history information give us an important clue as compared to age, gender and alcohol consumption parameters when predicting the number of blocked vessels. Conclusions: VPO1 and ATF4 might be potential biomarkers associated with coronary artery disease, especially in the follow-up and monitoring of treatment protocols, in addition to traditional risk factors.

Relationship between LPA SNPs and inflammatory burden in patients with preeclampsia to address future cardiovascular risk.

OBJECTIVE: The study tested whether cardiovascular corresponding LPA risk genotypes improve pre-eclampsia and coronary heart disease (CHD) risk prediction beyond conventional risk factors. BACKGROUND: Studies have shown that women specific risk factors for cardiovascular disease (CVD) have taken an attention recently. It might be possible to identify women who have the highest risk in developing CVD in their further lives. It is well-known that Lp(a) levels have an impact on increased risk of CVD which is affected by LPA gene. Further, LPA risk genotypes are not considered in cardiovascular risk prediction. METHODS: We have included 200 pregnant Turkish women into the study. We stratified the preeclamptic (PE) group: early (EOP) (28.7 ± 3.0 weeks) and late onset (LOP) (36.0 ± 1.4 weeks). 14 LPA SNPs were evaluated in the study. Rs9355296 and rs3798220 were found as independent risk factors for preeclampsia by logistic regression analysis. A positive correlation was found between rs9355296 and the diagnostic criteria of preeclampsia. Further rs9355296 G/* carriers have higher vascular inflammation rather than AA carriers. CONCLUSIONS: The findings reveal that LPA genetic variability with high inflammatory response might be an indication of future cardiovascular events.

Possible effects of lipoprotein-associated phospholipase A2 single-nucleotide polymorphisms on cardiovascular risk in patients with preeclampsia.

PURPOSE: Lipoprotein lipase-associated phospholipase A2 (Lp-PLA2) is a vascular inflammatory marker associated with cardiovascular diseases (CVD). Women with preeclampsia (PE) have elevated vascular inflammation and at higher CVD risk in the later life. We hypothesize that vascular inflammation related genetic variations increase the risk for developing future cardiovascular disease in women with PE. To test this hypothesis, we studied PLA2G7 gene polymorphisms, Lp-PLA2 mass, activity, index, and other cardiovascular risk factors in women with preeclampsia. METHODS: A total of 200 pregnant women were included into the study. We stratified the PE group: early (28.7 ± 3.0 weeks) and late onset (36.0 ± 1.4 weeks). Serum Lp-PLA2 mass in the early PE and the late PE group were significantly higher than the control group (p = .000). Lp-PLA2 index, Hs-C-reactive protein (CRP), serum amyloid A (SAA), calprotectin, and PTX3 levels were higher in early and late PE (p = .000). Single-nucleotide mutations of PLA2G7 rs1805017 (r = -0.228, p < .05) and rs9381475 (r = 0.216, p < .05) were correlated with LpPLA2 mass for the early PE group. Logistic regression analysis showed that LP-PA2 mass an independent risk factor for early PE with rs1805017 and rs9381475 carriers. CONCLUSIONS: Lp-PLA2 genetic variability with vascular inflammatory markers might contribute the incidence of future cardiovascular events.

The relationship between glomerular function and podocyte structure of pre-proteinuria and acute nephrosis in puromycin aminonucleoside-induced rat models: a comparative electron microscopic study.

Puromycin aminonucleoside (PA) has been generally utilized as model of podocyte injury followed by massive proteinuria, severe damage on endocytotic activity of epithelial cells and postmodification of endocytosed compounds. However, total PA nephrosis (PAN) mechanism cannot be understood. We aimed to study glomerular function, foot process degeneration and transport pathways of podocytes in pre-proteinuria and acute PAN rats. Eighteen male Wistar albino rats were divided into three groups: control, pre-proteinuria and acute nephrosis groups (n=6). PA was injected into pre-proteinuria group for three times and acute group for nine times. Proteinuria levels in urine, creatinine and albumin levels in blood were detected 24 hours after PA injections. Renal cortex samples were prepared for transmission electron microscopy. Proteinuria levels in acute group significantly elevated, whereas creatinine clearance, serum albumin levels and urine volumes diminished compared to control and pre-proteinuria groups. In pre-proteinuria group, hypertrophy and structurally rich cytoplasm were detected only within podocytes. Acute group had various protein absorption granules secreted from podocyte cytoplasm to the urinary space through exocytosis after lysosomal digestion; but not observed in pre-proteinuria group. The number of slit pores in pre-proteinuria group decreased, particularly related to fusion of foot processes, subsequently leading to proteinuria. We concluded that foot process fusion begins prior to development of proteinuria although their serum albumin and creatinine clearance levels do not differ significantly. Additionally, we suggested that in acute PAN, first affected glomerular cells could be podocytes and there could be a correlation between glomerular function and number of slit pores.

Is there any relationship between adipocytokines and angiogenesis factors to address endothelial dysfunction and platelet aggregation in untreated patients with preeclampsia?

PURPOSE: Preeclampsia is a multisystem disorder and its etiology remains still unclear. Recent hypotheses rely on imbalance between angiogenic and antiangiogenic factors and disruption of endothelial function of spiral arteries. In addition; increased VTE (venous thromboembolism) risk is still unclear in preeclampsia. Our aim was to investigate the relationship between endothelial dysfunction, adipocytokines, platelet function, and vasculogenesis in preeclampsia. METHODS: Plasma angiogenic (PlGF, VEGF), antiangiogenic factors (sflt-1, endoglin) with adipocytokines (leptin, adiponectin, ghrelin), endothelial dysfunction markers (vWF, NO), and platelet function markers (ADP and collagen induced platelet aggregation, P-selectin) were examined in 30 early-onset, 22 late-onset preeclampsia, and 27 healthy pregnants. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum biomarker levels except NO. NO levels were determined using colorimetric method. RESULTS: Endoglin, leptin, and vWF levels were increased in preeclampsia (P < 0.001), whereas PlGF, P-selectin (P < 0.001), and col-induced platelet aggregation slope (P < 0.05) were decreased in the same counterpart as compared to healthy pregnants. Endoglin also correlated with sflt-1 in preeclamptic patients. CONCLUSION: Increase in the levels of antiangiogenic factors and leptin herewith decline in the level of other angiogenic factor PlGF, did not affect nitric oxide and platelet aggregation markers significantly. Increased levels of vWF and endoglin might be result of endothelial dysfunction, so our findings suggest that an impaired angiogenesis may address endothelial dysfunction, but not platelet aggregation for preeclampsia.

Endothelial Dysfunction Markers in Low Cardiovascular Risk Individuals: Comparison of Males and Females.

BACKGROUND: Cardiovascular diseases (CVD) account for approximately 50% of the total deaths in Turkey. Most of them are related with atherosclerotic coronary heart disease. Predictive value of endothelial dysfunction markers related with the earliest stage of atherosclerosis has been getting more attention. We hypothesized that differences in endothelial dysfunction biochemical markers among genders would aid to capture proatherogenic activity that was not diagnosed by conventional risk assessment scoring systems. METHODS: We assessed the endothelial dysfuntion markers in 92 Turkish adults who were in the ¼low CV risk group« according to ESC (European Society of Cardiology)-Score Risk Charts. We compared the males and females. RESULTS: We observed higher endothelial dysfunction rates in males, with higher median and mean levels of e-NOS, ox-LDL before and after adjustment for HDL lowness and obesity (P=0.018, P=0.036 for NOS; P=0.000, P=0.004 for ox-LDL, respectively). Men had higher hs-CRP levels than females before adjustment (P=0.021). Decreased e-NOS levels were related with FMD for females before adjustment for confounders (P=0.028). We also found significant correlation between e-NOS and ox-LDL levels both before (r=0.360, P<0.001) and after adjustment (r=0.366, P<0.01) for confounders which pointed out the nitrosative stress. In multivariate regression analyses, after adjusting for other endothelial dysfunction markers which were not included in the ESC-risk scoring system, decreased e-NOS levels were independently asssociated with impaired flow mediated dilatation for females (odds ratio 0.3; P=0.038). CONCLUSIONS: Our results underline the importance of gender in evaluating endothelial dysfunction biochemical markers to assess cardiovascular risk for low CV risk indivuals.

Relation of Biochemical Parameters with Flow-mediated Dilatation in Patients with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is one of the high cardiovascular (CV) situations. Endothelial dysfunction, which is a common finding in patients with MetS, is related with increased CV risk. In patients with MetS, the effect of the major CV risk factors, not included in the MetS definition, on endothelial dysfunction is not well known. The aim of this study was to determine the effect of major CV risk factors such as gender, smoking, family history, and biochemical parameters on endothelial dysfunction in patients with MetS. METHODS: The study was performed between December 2010 and August 2014. A total of 55 patients (15 females and 40 males) with MetS and 81 healthy controls (37 females and 44 males) with a body mass index <25 kg/m2 were enrolled in the study. Endothelial dysfunction was measured by flow-mediated dilatation (FMD), oxidative stress parameters; high-sensitivity C-reactive protein (hs-CRP), oxidized low-density lipoprotein (ox-LDL), endothelial nitric oxide synthase (e-NOS), nitric oxide, and cell adhesion markers; von Willebrand factor, and e-selectin. Platelet aggregation (endothelial adenosine diphosphate), total platelet count, and mean platelet volume were additionally analyzed and demographic parameters were explored. Student's t- test, Mann-Whitney U-test, and Chi-square test were used to analyze the results. RESULTS: The fasting blood glucose (z= 3.52, P= 0.001), hs-CRP (z = 3.23, P= 0.004), ox-LDL (z = 2.62, P= 0.013), and e-NOS (z = 2.22, P= 0.026) levels and cardiac risk score (z = 5.23, P< 0.001) were significantly higher in patients with MetS compared with the control group. Smoking was correlated with decreased FMD (χ2 = 9.26, P= 0.002) in MetS patients but not in the control group. CONCLUSIONS: Increased ox-LDL, hs-CRP, and e-NOS are likely to be a result of oxidative stress, a condition in which an imbalance occurs between the production and inactivation of reactive nitrogen and oxygen species. In addition, in patients with MetS, smoking is independently related to endothelial dysfunction.

Evaluation of Lp-PLA2 mass, vitronectin and PAI-1 activity levels in patients with preeclampsia.

PURPOSE: The aim of the current study is to determine, correlate and compare the plasma lipoprotein-associated phospholipase A2 (Lp-PLA2), vitronectin (Vn), Plasminogen activator inhibitor-1 (PAI-1) activity and tissue plasminogen activator (t-PA) levels in early-onset preeclampsia, late-onset preeclampsia and in control pregnant women. METHODS: A total of 79 individuals, 30 early-onsets, and 22 late-onset preeclamptic and 27 control pregnant women were included into the scope of this study. Enzyme-linked immunosorbent assay procedure was used to determine the serum Lp-PLA2 and plasma Vn, t-PA antigen and PAI-1 activity levels. Serum C-reactive protein (CRP) levels were measured immunoturbidimetrically in routine clinical chemistry analyser. RESULTS: In patients with preeclampsia, Lp-PLA2, PAI-1, t-PA, CRP and blood pressures levels were increased (p = 0.000) and correlated with each other. Vn levels were decreased (p = 0.016) but not correlated with other parameters in preeclamptic patients. CONCLUSION: We are of the opinion that increased Lp-PLA2 levels may partially contribute to endothelial dysfunction by the progression of inflammation. In addition, increased complex formation with Vn is likely to bring about the increase of PAI-1 activity in patients with preeclampsia. Moreover, increased t-PA and decreased Vn levels may also be the consequences of compensatory mechanisms against disease progression.

Experimentally induced puromycine aminonucleoside nephrosis (PAN) in rats: evaluation of angiogenic protein platelet-derived endothelial cell growth factor (PD-ECGF) expression in glomeruli.

BACKGROUND: In experimentally induced puromycine aminonucleoside nephrosis (PAN) animal models, nephrotic syndrome with minimal change disease and focal and segmental sclerosis-like nephritis similar to that in human is demonstrated; however, the real mechanism of PAN is not yet elucidated. Platelet derived endothelial cell growth factor (PD-ECGF), an endothelial mitogen protein, is believed to take part in microvessel formation and in stimulation of angiogenesis and its expression has not been totally demonstrated in PAN rats yet. In this study, we aimed to examine PD-ECGF expression in acute and chronic PAN induced in rats and find out the association between its expression and the stages of angiogenesis in kidney. METHODS: For the experiment, twenty-four Male Wistar Albino rats were used and divided into four groups; control group (n = 6), pre-proteinuria group (n = 6), acute group (n = 6) and chronic group (n = 6). We compared statistically all data by One-way ANOVA Test followed by Dunn Multiple Comparison Test. RESULTS: Proteinurea levels in control and pre-proteinuria groups were not statistically different; however, it was remarkably higher in the acute nephrosis group and significantly greater in the chronic nephrosis group than control group (p < 0.0025). In pre-proteinuria group, the serum albumin and creatinine clearances also did not significantly differ from the control group. On the other hand, in the acute and chronic nephrosis groups, serum albumin and creatinine clearances progressively decreased (p < 0.05). In our immunohistochemical studies, we showed elevated PD-ECGF expression in glomeruli of acute and chronic PAN rats. Microscopic and ultrastructural appearances of the glomeruli of acute and chronic PAN showed various sequential steps of angiogenesis, macrophages and immature capillaries with primitive lumens and apoptotic endothelial cells in the increased mesangial matrix. CONCLUSIONS: It is reported that acute and chronic PAN progressively increase PD-ECGF expression and following induction of angiogenesis in the affected glomeruli.

Nontraditional risk factors in carotid artery disease.

Carotid atherosclerosis (AS) is one of the main risk factors for ischemic stroke. Our aim is to evaluate the nontraditional biochemical markers in asymptomatic and symptomatic patients with carotid artery plaque. This study was conducted on 55 patients: 43 with symptomatic and 12 with asymptomatic carotid artery disease. Lipoprotein (a) (Lp(a)), homocysteine, adiponectin, nitric oxide (NO), and tumor necrosis factor alpha (TNF-alpha) levels were measured in the plasma. The mean of total cholesterol, triglyceride, and homocysteine levels was significantly elevated in the symptomatic group as compared with the asymptomatic group (P = .03). In the asymptomatic group, adiponectin and NO levels showed elevations as compared with the symptomatic group but this increase was not significant (P > .05). Lipoprotein (a) and TNF-alpha levels acted inversely with adiponectin and NO. There was an insignificant decline in Lp(a) and TNF-alpha levels in the asymptomatic group as compared with the symptomatic group (P > .05).

Effects of serum homocysteine and adiponectin levels on platelet aggregation in untreated patients with essential hypertension.

The aim of the present study is to determine and correlate adiponectin, homocysteine, nitric oxide, and ADP-induced platelet aggregation levels in untreated patients with essential hypertension and healthy individuals. A total of 36 individuals, 23 untreated patients with essential hypertension and 13 healthy individuals, were included in the scope of this study. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum adiponectin and TNF-alpha levels. The levels of serum homocysteine were measured by using competitive chemiluminescent enzyme immunoassay. Serum concentrations of hsCRP were measured by the Nephelometer. Plasma nitrite, nitrate, and total nitric oxide (NOx) levels were determined by colorimetric method. Homocysteine and hsCRP levels in patients with essential hypertension were found to be significantly higher than those in the control group (P = 0.02, P = 0.001, respectively). The average platelet aggregation levels in patient group were higher than control group, but there were no statistically significant differences between them (P > 0.05). In addition, in patients with essential hypertension adiponectin and nitrite levels are significantly lower than control group (P < 0.001, P = 0.045, respectively). We have also found significant correlations between nitrite-platelet aggregation amplitude, nitrite-platelet aggregation slope, nitrite-adiponectin, homocysteine-platelet aggregation amplitude, and sistolic blood pressure-platelet aggregation amplitude levels (r = -0.844; P < 0.001, r = -0.680; P = 0.011, r = 0.454; P = 0.05, r = 0.414; P = 0.05, r = 0.442; P = 0.035, respectively). Increased homocysteine and decreased adiponectin serum levels in patients with essential hypertension correlate well with changes in ADP-induced conventional platelet aggregation. This association may potentially contribute to future thrombus formation and higher risks for cardiovascular events in hypertensive patients.

Preliminary study showing the relationship between platelet fibronectin, sialic acid, and ADP-induced aggregation levels in coronary heart disease.

Several studies indicate that thrombosis plays an important role in the pathogenesis of coronary heart disease (CHD). Fibronectin is a multifunctional protein in plasma, other body fluids, and cell surface and plays an important role in platelet functions, including mediation of cell-cell and cell-surface interactions. Sialic acid is a regular constituent of glycoproteins and gangliozides in the outer cell membrane of mammalian cells. Therefore, the sialic acid content of platelets, which are characterized by their ability to aggregate with each other, can be important in leading to thrombus formation. In this study, platelet fibronectin, sialic acid-, and adenosine diphosphate (ADP)-induced platelet aggregation levels were determined in patients with CHD. Platelet sialic acid concentrations were determined by Warren's method. Platelet aggregation tests with ADP in platelet-rich plasma (PRP) were analyzed by use of an aggregometer. Platelet homogenate fibronectin levels were determined by ELISA. Total protein levels were determined by Lowry method. Our results indicate that, in patients with no vessel disease (patients with no obstructed vessel but suffering from chest pain, like angina pectoris) platelet fibronectin levels were significantly lower than the total of the other patients (patients with 1, 2, or 3 obstructed coronary vessels) (p<0.05). Sialic acid levels in patients with no vessel disease were significantly lower than the total of the patient group (p<0.05). There was significant (+) correlation between platelet aggregation, platelet fibronectin, platelet sialic acid, and severity of disease (p<0.05). Our preliminary findings suggest that, especially platelet fibronectin levels potentially represent a pathogenic factor for CHD.

The Relationship Between Lipid Peroxidation and LDL Desialylation in Experimental Atherosclerosis.

ABSTRACT High serum total cholesterol concentration has been strongly connected with atherosclerosis in numerous studies. Being the main carrier of cholesterol in blood, low-density lipoprotein (LDL) is also the principal lipoprotein causing atherosclerosis. Sialic acids are a family of amino sugars that are commonly found as terminal oligosaccharide residues on glycoproteins and are sialylated on their apolipoprotein and glycolipid constituents. In several studies, it was demonstrated that LDL has a 2.5- to 5-fold lower content of sialic acid in patients with coronary artery disease compared with healthy subjects. The role of oxidatively modified LDL in the pathogenesis has been well documented. These studies have focused on modifications in the lipid and protein parts of LDL. But recently, desialylated LDL and its relation with the oxidation mechanisms have received attention in the pathogenesis of atherosclerosis and coronary artery disease (CAD). From these points, we have performed atheroma plaques in an experimental atherosclerosis model with rabbits and examined the LDL and plasma sialic acid and thiobarbituric acid reactive substance (TBARS) levels in the same model. We also have determined serum sialidase enzyme activities relevant with these parameters. LDL sialic acid levels were significantly decreased in the progression of the atherosclerosis (by the 30th, 60th, and 90th days). LDL and plasma TBARS levels and plasma sialidase enzyme activities were significantly elevated by the same time periods. In conclusion, serum sialidase enzyme may play an important role in the desialylation mechanism, and reactive oxygen substance (ROS) may affect this reaction.

Comparison of platelet fibronectin, ADP-induced platelet aggregation and serum total nitric oxide (NOx) levels in angiographically determined coronary artery disease.

INTRODUCTION: Coronary thrombosis is an important determinant of prognosis in patients with acute coronary syndromes. Fibronectin is also found in platelets within the alpha secretory granules and secreted following platelet stimulation by a variety of agonist. Available data suggest that expression of platelet fibronectin on the cell surface may indicate a role in platelet aggregation and adhesion to fibrin thrombi and connective tissue. Clear evidence has emerged that a concerted action of nitric oxide (NO) generated by either endothelial or platelet NO synthases regulates platelet activation, causing inhibition of adhesion and aggregation. The aim of the present study was determining and correlating the serum total NO (NOx), platelet fibronectin and ADP-induced platelet aggregation levels in coronary artery disease (CAD) patient subgroups. MATERIALS AND METHODS: A total of 43 coronary artery disease patients were included in this study. Peripheral blood samples from patients with coronary artery disease were obtained from the Department of Cardiology. Platelet aggregation tests with adenosine diphosphate (ADP) were analyzed by using aggregometer. Platelet fibronectin concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Serum total nitric oxide (NOx) levels were determined by colorimetric method. RESULTS: In patients with double-vessel disease, platelet fibronectin levels were found to be significantly higher than no-vessel disease (p<0.001), single-vessel disease (p<0.01) and triple-vessel disease (p<0.001). In addition, in patients with single-vessel disease platelet fibronectin levels significantly higher than no-vessel disease (p<0.05). We could not find any significant differences in ADP-induced platelet aggregation and serum NOx values between CAD patient subgroups. There was a positive correlation between platelet fibronectin levels and severity of disease (r=0.315, p<0.05).

Evaluation of fibronectin, vitronectin, and leptin levels in coronary artery disease: impacts on thrombosis and thrombolysis.

In this study, the levels of fibronectin, vitronectin, leptin, tissue plasminogen activator (t-PA), and lipid parameters were investigated in patients with coronary artery disease (CAD) and control group. The average plasma fibronectin levels in CAD patients group were significantly higher compared with the control group (p=0.006). Moreover, in patients with triple-vessel disease, plasma fibronectin levels were found to be significantly higher than those in the control group (p<0.05). Plasma vitronectin levels in patients with CAD were found to be significantly higher than those in the control group (p=0.000). In addition, in patients with double vessel disease plasma vitronectin levels were significantly higher than no vessel disease and control group, triple vessel disease was significantly higher as compared with no vessel disease, single vessel disease, and control group (p<0.05). We could not find any significant differences in t-PA values between CAD patients and control group. On the other hand, the average leptin levels in the group of patients were higher than those in the control group but there were no statistically significant differences found between them (p>0.05) because of high SD values. There was strong (+) correlation between fibronectin, vitronectin, and severity of disease [vitronectin/severity of disease, r = 0.5074 (p = 0.000), fibronectin/severity of disease, r = 0.2971 (p = 0.007)]. In conclusion, we can say that fibronectin and vitronectin have become greatly important in pathogenesis of coronary artery disease. High leptin levels may be contribute to platelet aggregation in patients with coronary artery disease. But, elevated serum levels of leptin cannot be useful diagnostic and monitoring markers in patients with coronary artery disease.

The relationship of TFPI, Lp(a), and oxidized LDL antibody levels in patients with coronary artery disease.

OBJECTIVES: The aim of the present study was to determine and correlate tissue factor pathway inhibitor (TFPI), lipoprotein (a) (Lp(a)), oxidized low-density lipoprotein (LDL) antibody (oLAB), and thiobarbituric acid reactive substances (TBARS; as a marker of lipid peroxidation) levels in patients with coronary artery disease (CAD) and in a control group. DESIGN AND METHODS: Peripheral blood samples from patients with coronary heart disease were provided by the Department of Cardiology. Serum oLAB, Lp(a), plasma total TFPI, and plasma-free TFPI levels were determined by ELISA. Serum TBARS levels were determined by a spectrophotometric method using thiobarbituric acid. RESULTS: The CAD and the control group were matched for age and sex. Serum Lp(a), oLAB, and plasma total TFPI levels in patients with coronary heart disease were found to be significantly higher than in the control group (P < 0.001). But there was no difference in plasma-free TFPI levels between patients with CAD and the control group (P > 0.05). In patients with single (P < 0.05), double, and triple vessel (P < 0.01) disease, the mean serum Lp(a) levels were significantly higher than in the control group. On the other hand, in patients with single vessel disease (P < 0.05), double vessel disease (P < 0.05), and triple vessel disease (P < 0.001), plasma total TFPI levels were found to be significantly higher than in the control group. We also found a significant positive correlation (r = 0.28, P < 0.05) between serum Lp(a) and plasma total TFPI levels in CAD. In the patient group, TBARS, total cholesterol, triglyceride (TRG), and LDL cholesterol levels were found to be significantly higher than those in the control group. In addition, high-density lipoprotein (HDL) cholesterol levels were found to be significantly lower than the control group. CONCLUSIONS: These results suggest that elevated plasma levels of total TFPI, Lp(a), and oLAB may be useful diagnostic and monitoring markers in patients with CAD.

Plasma vitronectin levels in patients with coronary atherosclerosis are increased and correlate with extent of disease.

BACKGROUND: Acute thrombosis after atherosclerotic plaques disruption is a major complication of primary atherosclerosis, leading to acute ischemic syndromes and atherosclerotic progression. Vitronectin (VN) is multifunctional glycoprotein in blood and in the extracellular matrix. It binds glycosaminoglycans, collagen, plasminogen and urokinase receptor. VN stabilizes the inhibitory confirmation of plasminogen activation inhibitor-1 (PAI-1). Vitronectin may control the clearance of vascular thrombi by binding and stabilizing PAI-1, a key regulator of fibrinolysis. Therefore, VN is generally regarded as a cofactor for PAI-1 activity. On the other hand vitronectin binds to platelet glycoproteins may mediate platelet adhesion and aggregation at sites of vascular injury. Previous studies showed that anti-VN antibodies inhibit platelet aggregation in vitro, suggesting that vitronectin contributes to platelet accumulation at sites of vascular injury. In this study; we investigated the levels of plasma vitronectin in patients with Coronary Artery Disease (CAD) and control group. METHODS: The patient group was divided into four subgroups: patients with no, single, double and triple vessel disease according to their angiography results. ELISA procedure (Technoclone) was used to determine the plasma vitronectin levels. RESULTS: Plasma vitronectin levels in patient with CAD (% 125.87 +/- 58.38) were found to be significantly higher than control group (% 89.47 +/- 25.3) (p:0.000). In addition, in patients with double vessel disease (% 146.03 +/- 71.69) plasma vitronectin levels were significantly higher than no vessel disease (% 87.84 +/- 22.30) and control group, triple vessel disease (% 160.81 +/- 57.02) significantly higher as compare with no, single vessel disease (% 111.68 +/- 45.34) and control group (p < 0.05). There was no correlation between vitronectin and lipid parameters. CONCLUSION: These findings suggested that vitronectin is a marker of CAD. Elevated levels may indicate its role in the genesis and/or progression of CAD or may be the results of a compensatory mechanism.

Looking for Our Ten Years Results for Coronary Heart Disease and Ischemic Stroke Group for the Standpoint of Haemostasis.

To evaluate the role the coagulation and fibrinolysis abnormalities in the pathogenesis of ischemic stroke of undetermined etiology, we assayed plasma concentration of fibrinopeptide-A and thrombin-antithrombin III complex, both sensitive markers for thrombin activation and fibrin formation, and D-dimer, a marker of plasmin activity and fibrinolysis. Hemostatic markers were measured in 32 patients with acute stroke and 20 patients with chronic stroke, and compared with 21 normal subjects. Fibrinopeptid-A and thrombin-antithrombin III complex levels were not elevated significantly, whereas the D-dimer level was markedly raised in acute (p<< 0.001) and chronic (p< 0.05) phases of ischemic stroke in comparison with the control group. Prolonged elevation of D-dimer concentration suggests that hemostatic abnormalities have a primary role in the pathogenesis of ischemic stroke. The measurement of D-dimer concentration may help to better decide the indications for therapy of the patients with ischemic stroke of undetermined etiology.