Plasma Levels Of Platelet-derived Growth Factor Research Articles

The prediction value of platelet-derived growth factor for major adverse cardiovascular events in patients with acute non-ST-segment elevation myocardial infarction

Background The value of plasma Platelet-Derived Growth Factor (PDGF) as a biomarker in predicting major adverse cardiovascular events (MACEs) in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear. Methods A total of 242 patients with NSTEMI were enrolled in this observational cohort study. The correlation between PDGF and MACEs was evaluated during a five-year follow-up. Kaplan–Meier survival analysis with Cox proportional-hazards regression was used to identify predictive values of PDGF. Results The mean follow-up of NSTEMI patients was 1334 days. It was found that as the PDGF level increased, a significant uptrend in the incidence of MACEs and all-cause death, including the MACEs of 30 days, 180 days, 1 year, 5 years and the death of 1 year and 5 years (All Log-rank p < .05). Subgroup analysis further showed that PDGF had better predictive value for patients with age >65 years, GRACE score ≥140 and platelet count (PLT) >200 × 109/L. Conclusion PDGF levels can predict short-term and long-term MACEs in NSTEMI patients after discharge, especially for patients with older age, higher GRACE score and baseline PLT > 200 × 109/L. Key messages PDGF is a risk factor for short- and long-term MACEs in patients with STEMI. PDGF has a better prognostic value in patients with older age and PLT > 200 × 109/L. Baseline plasma PDGF levels were positively correlated with GRACE score.

Transcriptional Dysregulation Underlies Both Monogenic Arrhythmia Syndrome and Common Modifiers of Cardiac Repolarization.

Brugada syndrome (BrS) is an inherited arrhythmia syndrome caused by loss-of-function variants in the cardiac sodium channel gene SCN5A (sodium voltage-gated channel alpha subunit 5) in ≈20% of subjects. We identified a family with 4 individuals diagnosed with BrS harboring the rare G145R missense variant in the cardiac transcription factor TBX5 (T-box transcription factor 5) and no SCN5A variant. We generated induced pluripotent stem cells (iPSCs) from 2 members of a family carrying TBX5-G145R and diagnosed with Brugada syndrome. After differentiation to iPSC-derived cardiomyocytes (iPSC-CMs), electrophysiologic characteristics were assessed by voltage- and current-clamp experiments (n=9 to 21 cells per group) and transcriptional differences by RNA sequencing (n=3 samples per group), and compared with iPSC-CMs in which G145R was corrected by CRISPR/Cas9 approaches. The role of platelet-derived growth factor (PDGF)/phosphoinositide 3-kinase (PI3K) pathway was elucidated by small molecule perturbation. The rate-corrected QT (QTc) interval association with serum PDGF was tested in the Framingham Heart Study cohort (n=1893 individuals). TBX5-G145R reduced transcriptional activity and caused multiple electrophysiologic abnormalities, including decreased peak and enhanced "late" cardiac sodium current (INa), which were entirely corrected by editing G145R to wild-type. Transcriptional profiling and functional assays in genome-unedited and -edited iPSC-CMs showed direct SCN5A down-regulation caused decreased peak INa, and that reduced PDGF receptor (PDGFRA [platelet-derived growth factor receptor α]) expression and blunted signal transduction to PI3K was implicated in enhanced late INa. Tbx5 regulation of the PDGF axis increased arrhythmia risk due to disruption of PDGF signaling and was conserved in murine model systems. PDGF receptor blockade markedly prolonged normal iPSC-CM action potentials and plasma levels of PDGF in the Framingham Heart Study were inversely correlated with the QTc interval (P<0.001). These results not only establish decreased SCN5A transcription by the TBX5 variant as a cause of BrS, but also reveal a new general transcriptional mechanism of arrhythmogenesis of enhanced late sodium current caused by reduced PDGF receptor-mediated PI3K signaling.

Evaluation of plasma PDGF and VEGF levels after systemic administration of activated autologous platelet-rich plasma

Introduction and Aim: Activated autologous platelet-rich plasma (aaPRP) is becoming a popular therapy to accelerate healing in the field of plastic surgery. Platelets, which are abundant in aaPRP, can release many growth factors including platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). This study aims to examine the plasma levels of PDGF and VEGF in healthy subjects after intravenous administration of aaPRP.&#x0D; &#x0D; Materials and Methods: Nine healthy patients with no prior history of metabolic disease were divided into two groups (control and experiment group). The treatment group which consists of six patients received intravenous aaPRP treatment. The preparation of aaPRP starts with the collection of 24 mL of whole blood in sodium citrate tubes followed a two-step centrifugation procedure and subsequent chemical activation. aaPRP was then administered intravenously to patients. Meanwhile, the control group received no intervention. Venous blood samples were taken before and one week after the treatment and the plasma PDGF and VEGF levels were determined by enzyme-linked immunosorbent assay (ELISA).&#x0D; &#x0D; Results: The treatment group showed statistically significant increase in VEGF after 7 days compared to before aaPRP administration. However, the change in PDGF levels of the treatment group was unnotable.&#x0D; &#x0D; Conclusion: The present findings indicate that intravenous administrations of activated aaPRP may increase plasma VEGF level up to 1 week after aaPRP administration.

Levels of angiogenic proteins in plasma and platelets are not different between patients with hepatitis B/C-related cirrhosis and patients with cirrhosis and hepatocellular carcinoma

Increasing evidence suggests that levels of angiogenic proteins within blood platelets change at the earliest stages of cancer development and may thus provide a promising diagnostic and prognostic tool. Patients with cirrhosis have increased risk of developing hepatocellular carcinoma (HCC). We aimed to study whether development of HCC in hepatitis-related cirrhosis results in changes in platelet levels of angiogenic proteins. We studied the intraplatelet levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), endostatin, platelet factor 4 (PF4) and thrombospondin type 1 (TSP-1) in 38 consecutive patients with hepatitis B- or C-related liver cirrhosis with or without HCC in addition to plasma levels of the same proteins. Twenty healthy volunteers were included to establish reference values for the various tests. Intraplatelet levels of VEGF, bFGF, HGF and endostatin were significantly higher in patients compared to controls. Intraplatelet levels of PDGF, PF4 and TSP-1 were comparable between patients and controls. Plasma levels of VEGF, bFGF and endostatin were comparable between patients and controls. Plasma levels of PDGF, PF4 and TSP-1 were decreased in patients, but this difference disappeared when levels were corrected for platelet count. Intraplatelet and plasma levels of all proteins assessed were comparable between patients with and without HCC. In conclusion, the intraplatelet levels of some angiogenic proteins are elevated in cirrhosis, but do not discriminate between patients with and without HCC. Thus, intraplatelet levels of angiogenic proteins do not seem useful as diagnostic or prognostic biomarker of HCC in cirrhotic patients.

Role of Platelet-Derived Growth Factor On Vascular Endothelial Growth Factor Synthesis by Mesenchymal Stem Cells in Chronic Lymphocytic Leukemia: Implications for Clinical Progression.

Abstract 804 Background:We have demonstrated that crosstalk between CLL B-cells and marrow-derived mesenchymal stem cells (MSC) can modulate the activation of both. Soluble factors in the CLL-condition media (CM) regulate the migration and proliferation of MSC. We previously found that platelet-derived growth factor (PDGF) receptors were selectively activated in MSC by CLL-CM and are necessary for the downstream Akt activation in MSC. PDGF is capable of promoting vascular endothelial growth factor (VEGF) production in MSC; however, several questions remain unanswered. Can CLL B-cells produce PDGF; is PDGF the specific mediator in CLL-CM responsible for PDGFR activation in MSC; what is the mechanism of PDGF mediated VEGF production in MSC; and is there any clinical significance of PDGF mediated VEGF production by MSC for CLL patients? Methods:MSC were generated from CLL patients and controls as previously described. To determine the specific ligand responsible for PDGFR activation mediated by CLL-CM blocking antibody to PDGF or VEGF or both was used to neutralize the binding activity of PDGF or VEGF in the CLL-CM. Subsequently, the pattern of membrane receptor activation was evaluated using a commercially available receptor tyrosine kinase (RTK) array assay. ELISA was performed to measure PDGF and VEGF levels from plasma and CM of CLL patients and normals. The protein expression of PDGF isoforms in CLL and normal B-cells was assessed using Western blot. To assess the mechanism of PDGF mediated VEGF production by MSC, we used either a PI3K inhibitor, LY294002 (20 mM), or a p38 MAPK inhibitor, SB202190 (100 nM), to block these pathways in MSC. Results:The known ligands for PDGF receptors, PDGF and VEGF, were detected in the CLL-CM (PDGF, 113.7 ± 23.6 pg/ml, VEGF, 186.94 ± 54.57 ng/ml; n = 12). We also found that PDGF is present in CLL cells by Western blot analysis and expression of PDGF in CLL cells was up regulated by hypoxia. By using PDGF- or VEGF-blocking antibody or both to neutralize the binding activity of PDGF or VEGF in CLL-CM, we found only PDGF-blocking antibody was able to neutralize the majority of PDGFRa activation, indicating that PDGF in the CM is the predominant ligand for PDGFR activation in MSC. CLL MSC was exposed to either pooled CLL (n = 5) or pooled normal plasma (n = 5). Interestingly, PDGFR was more potently activated by CLL plasma than the normal plasma, suggesting PDGF levels were elevated in the CLL plasma. Indeed, PDGF in the normal plasma appeared to be much lower compared to the CLL plasma [normal (n = 11): 554.43 ± 88.55 pg/ml; CLL (n=43): 3115.36 ± 428.79 pg/ml. p < 0.0001]. In addition, the plasma PDGF level was found to be weakly correlated with VEGF level in 43 CLL patients assessed using Spearman correlation analysis (r = 0.3, p = 0.001). However, when CLL patients were grouped by clinical prognostic factors, the plasma PDGF level was found to be strongly correlated with plasma VEGF level in CLL patients with high-risk features including more advanced Rai stage 2-4 (r = 0.87, p < 0.0001), ZAP-70 positive (r = 0.8, p =0.04) and CLL patients who had required treatment (r = 0.8, p = 0.0008). To examine the mechanism for PDGF augmentation of VEGF by MSC, we found that PI3K pathway interruption using LY294002 (n = 6, p = 0.04), but not p38 MAPK inhibition (n = 6, p = 0.5), was able to abrogate the PDGF mediated VEGF production in MSC. Importantly, we also found that the secreted VEGF level in the CM of unstimulated CLL MSC appeared to be significantly higher compared to the level from culture media of unstimulated normal MSC [CLL (n = 14) vs. normal (n = 5), 298.1± 61.2 vs. 109.9 ± 52.3, p = 0.03]. Conclusions:These results indicate that PDGF secreted by CLL B-cells is necessary for PDGFR activation in MSC and can lead to increased VEGF production by MSC via a PI3K-Akt dependent mechanism. These findings have clinical implications as plasma PDGF levels are strongly correlated with plasma VEGF levels in high risk CLL. The finding that CLL MSC are more prone to secrete VEGF than normal MSC suggests the stromal microenvironment may function to facilitate CLL disease progression. Finally, as VEGF is known to enhance CLL B-cell survival and drug resistance, interrogation of the PDGF-VEGF regulation in the microenvironment of CLL patients should yield important information that can be used for therapeutic strategies in CLL. Disclosures:Kay:Biogenc-Idec, Celgene, Genentech, genmab: Membership on an entity's Board of Directors or advisory committees; Genentech, Celgene, Hospira, Polyphenon Pharma, Sanofi-Aventis: Research Funding.

Inverse correlation between activated protein C generation and carotid atherosclerosis in Type 2 diabetic patients

Activated protein C (APC) is a key regulator of the clotting system and immune responses. We studied the relationship between the degree of atherosclerosis as measured by the intima-media thickness (IMT) of carotid artery and APC generation in Type 2 diabetic patients. Eighty-seven Type 2 diabetic patients and 35 control subjects participated. APC generation was assessed by the plasma APC-protein C inhibitor complex (APC-PCI) levels and the mean IMT of carotid artery was measured by ultrasonography. The plasma levels of the thrombin-anti-thromobin complex (TAT) and platelet-derived growth factor (PDGF) were measured by enzyme-linked immunoassays. Plasma TAT levels were significantly higher in diabetic patients [2.03 (1.12, 2.56) ng/ml, median (25th, 75th percentile)] compared with control subjects [0.85 (0.55, 2.08) ng/ml, P < 0.01]. Plasma APC-PCI levels were significantly lower in diabetic patients [0.93 (0.74, 1.22) ng/ml], than in control subjects [1.66 (1.25, 2.36) ng/ml, P < 0.001]. The mean IMT was significantly increased in diabetic patients (0.881 +/- 0.242 mm; mean +/- sd) compared with control subjects (0.669 +/- 0.140 mm; P < 0.01). Univariate analysis showed a significant and inverse correlation between plasma APC-PCI levels and mean IMT (r = -0.32, P < 0.005), and multivariate regression analysis confirmed the independent correlation (P < 0.05). Moreover, plasma APC-PCI levels significantly and inversely correlated with plasma PDGF levels in diabetic patients (r = -0.30, P < 0.01). These results suggest that decreased APC generation is associated with vascular atherosclerotic changes in Type 2 diabetic patients.

Blood platelet count and reactivity are associated with restenosis 6 months after coronary angioplasty

Objectives—Restenosis occurs in 40–50% of patients treated with percutaneous transluminal coronary angioplasty (PTCA). Some data indicate that platelet derived growth factor (PDGF) plays a pathogenetic role. The aims of the present study were to measure the plasma levels of PDGF across the coronary circulation during PTCA and relate them to the development of restenosis.Design and results—Blood samples from the aortic root and coronary sinus were drawn simultaneously before, and after completed PTCA in 26 patients. Plasma levels of PDGF and beta‐thromboglobulin (BTG), as well as platelet counts were measured. Restenosis was evaluated by quantitative coronary angiography after 6 months. Significant increases both in PDGF and BTG were encountered in the aortic root after PTCA in patients who developed restenosis as compared to patients without restenosis. Patients who developed restenosis also had significantly higher platelet counts compared to those without.Conclusion—Increases in plasma PDGF and BTG in the aortic root after PTCA seem to be markers for restenosis 6 months after PTCA. This finding may strengthen the hypothesis that platelets contribute to the process of restenosis.

Increased platelet-derived growth factor (PDGF) release after laparotomy stimulates systemic tumor growth in mice.

Our laboratory has demonstrated that tumors grow larger and are more easily established following laparotomy than after carbon dioxide (CO2) pneumoperitoneum or anesthesia alone. We have also shown that tumor cells incubated with serum from laparotomized mice proliferated significantly faster in vitro than those incubated with plasma from mice that underwent laparoscopy or anesthesia alone. We hypothesized that differing levels of a plasma-soluble growth factor(s) postoperatively causes tumors to proliferate faster after laparotomy. This study's purpose was to isolate and characterize the plasma growth factor(s) responsible for the increased growth of systemic tumors after laparotomy. Female Balb/C mice (n = 100) were randomized to two groups: anesthesia control (AC) or midline sham laparotomy (4 cm) (Open). Plasma was collected on Postoperative day 4. For the tumor proliferation assay, C-26 colon cancer cells were incubated in media with either 10% AC or Open "raw" plasma (not passed through column), or AC or Open plasma that had been passed through the column. For elution of heparin-binding proteins, plasma from each group was passed through a heparin-sepharose column. Elution of bound proteins was accomplished with a 0.1-2 M NaCl gradient. Each fraction was examined for protein content. For the anti-platelet-derived growth factor (PDGF) neutralizing antibody study, C-26 cells were incubated with one of four plasma preparations: AC or Open plasma alone, or AC or Open plasma incubated with anti-PDGF antibody. For both studies, tumor proliferation was determined after 2 days with an MTS/PMS assay. Results from each group were compared and differences determined using analysis of variance (ANOVA) and Tukey-Kramer tests. On heparin chromatography, a single elution peak consistent with PDGF was present in both AC and Open plasma and was 1.5 times greater in the Open plasma. The first tumor proliferation assay showed that tumor cells incubated with Open plasma proliferated 2.5 times faster than those with AC plasma (p < 0.0001). Passage of AC plasma through the column did not alter its mitogenic activity, but Open plasma thus treated demonstrated significantly decreased mitogenic activity. The second tumor proliferation assay showed that anti-PDGF antibody had no effect on the mitogenic activity of the AC plasma but decreased the mitogenic activity of the Open plasma to the AC plasma level. Laparotomy is associated with higher levels of a heparin-binding plasma factor, consistent with PDGF. The enhanced mitogenic activity of the OP plasma was neutralized with anti-PDGF antibody. Increased plasma levels of PDGF after laparotomy may be responsible for accelerated tumor growth following laparotomy in mice.

Plasma platelet-derived growth factor: preliminary study of a potential marker in head and neck cancer.

The role of growth factors in the development and spread of head and neck cancers has received little attention. Platelet-derived growth factor (PDGF) is a potent mitogen that is released normally in wound healing, but is also secreted by human malignant epithelial cells. In breast and ovarian carcinomas, elevated plasma PDGF has correlated with a poorer prognosis. This preliminary study was designed 1) to determine if PDGF is elevated in the plasma of patients with squamous cell carcinoma of the head and neck and 2) to determine whether there is any change in levels following surgical ablation. The PDGF was measured by radioimmunoassay in 18 patients with head and neck squamous cell carcinoma and in 12 normal controls. In the control group the mean level was 7.4 fmol/100 microL (range 2.8 to 12.5, median 7.6), in spite of the fact that PDGF is reportedly not measurable in normal subjects. The mean PDGF level in the cancer patients was 20.4 fmol/100 microL (range 4.1 to 35.7, median 20.5) and as compared to the control group was significantly elevated (median two-sample test, p < .001). Of the 20 cancer patients, only 4 had levels less than 12.5 fmol/100 microL. Moreover, 2 of these had undergone prior radiotherapy. In all cases, PDGF levels decreased significantly after surgery. These results support the importance of the further investigation of plasma PDGF levels as a potential biomarker to evaluate efficacy of treatment, possibly to aid in the detection of tumor recurrence, and even to be a potential indicator of tumor aggressiveness.

Platelet-Derived Growth Factor (PDGF) in Patients with Different Degrees of Chronic Arterial Obstructive Disease

Platelet activation and platelet-derived growth factor (PDGF) play a pivotal role in the pathogenesis of atherosclerosis. Evidence has been accumulating that in the evolution of chronic arterial obstructive disease (CAOD) platelets are also crucially important. The aim of the present study was, therefore, to assess plasma levels of PDGF in patients with different degrees of CAOD according to Fontaine. Twenty patients (17 men, 3 women, mean age sixty-eight +/- seven years) with intermittent claudication (Fontaine stage II) entered the study and their PDGF levels were assessed by radioimmunoassay. Ten additional patients (7 men, 3 women, mean age seventy-three +/- seven years) with more severe CAOD (leg pain at rest/skin ulcers) were also studied. Ten healthy subjects (6 men, 4 women, mean age fifty-four +/- six years) comprised the control group. Patients in stage II were reinvestigated after sixty days of a "training" procedure. Patients with both intermittent claudication and more severe disease had higher levels of PDGF than controls (controls 165.9 +/- 119.1 pg/mL; Fontaine stage II 403.5 +/- 218.4; Fontaine stage III/IV 578.1 +/- 637.2: ANOVA P = 0.04) with no difference between the two groups of patients. After the training period, PDGF levels were significantly higher than at baseline (863.7 +/- 819.6 pg/mL vs 403.5 +/- 218.4) but without significant improvement of physical performance. The elevation of PDGF levels in blood from CAOD patients could be the result of marked platelet activation due to interaction with a widely damaged peripheral vasculature. The same was not true for coronary heart disease, in which normal values of PDGF in venous blood were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Positive immunostaining for platelet derived growth factor (PDGF) is an adverse prognostic factor in patients with advanced breast cancer

Previous studies suggest a prognostic role for PDGF in patients with breast cancer, with patients with high plasma PDGF levels or positive response to therapy. We have examined a further 58 patients with advanced breast cancer for the presence of tissue PDGF immunostaining. Patients displaying positive tissue immunostaining for PDGF had a highly significant shorter survival (p = 0.002) than patients with no immunostaining. In addition PDGF positive patients treated with combination chemotherapy had a significantly lower response rate (p = 0.05) than PDGF negative patients. These results confirm our previous findings that PDGF may be an important indicator of shortened survival and treatment failure in patients with advanced breast cancer.

Platelet-derived growth factor is released into the coronary circulation after coronary spasm.

Platelet-derived growth factor (PDGF) is a potent mitogen for vascular smooth muscle cells and is implicated in the vascular response to injury and the pathogenesis of atherosclerosis. It is also a potent vasoconstrictor. To examine whether acute myocardial ischemia increases the level of PDGF in the coronary circulation, we measured plasma levels of PDGF in the coronary sinus and the aortic root simultaneously in 14 patients with coronary spastic angina. These measurements were performed before and after the left coronary artery spasm induced by intracoronary injection of acetylcholine, and measurements were also taken in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Eleven patients with chest pain but normal coronary arteries and no coronary spasm served as controls. Plasma PDGF levels increased significantly (P < 0.01) from 274 +/- 28 pg/mL to 364 +/- 27 pg/mL only in coronary sinus after anginal attacks in the patients with coronary spastic angina. However, plasma PDGF levels in coronary sinus remained unchanged after these attacks in the patients with stable exertional angina (from 230 +/- 27 pg/ml to 247 +/- 28 pg/mL) and after intracoronary injection of acetylcholine in the control subjects. Plasma PDGF levels in aortic root remained unchanged in all three patient groups. PDGF is released into the coronary circulation after coronary artery spasm, and this may exacerbate coronary artery spasm.

Immunoassay of platelet-derived growth factor in the plasma of patients with scleroderma.

It has been postulated that platelet-derived growth factor (PDGF) is responsible for the abnormal fibroblast proliferation observed in scleroderma. In one previous study, plasma samples from patients with scleroderma caused increased mitogenesis in cultured fibroblasts, suggesting that the pathogenesis of scleroderma is related to increased plasma PDGF concentrations. To test this hypothesis, we used a sensitive, monoclonal antibody-based ELISA to measure PDGF in the plasma of 12 scleroderma patients. A rigorous sampling protocol prevented false elevations in plasma PDGF levels from ex vivo platelet degranulation: beta-thromboglobulin concentrations were measured in each plasma sample to monitor platelet lysis. Plasma PDGF concentrations in the scleroderma patients were not statistically different from those observed in age- and sex-matched normal controls, and patients with RA. While it is possible that changes in PDGF activity at a local level alter fibroblast function, we cannot conclude that elevated plasma concentrations of PDGF play a role in the pathogenesis of scleroderma.

Tissue platelet derived-growth factor (PDGF) predicts for shortened survival and treatment failure in advanced breast cancer.

In a study of plasma and tissue platelet derived growth factor (PDGF) concentration in patients with breast cancer, elevated levels of plasma PDGF were found in a significant proportion, 11/37 (30%), of patients. Sixteen patients (43%) had tumors which expressed PDGF-AA and 6 patients had tumors which in addition expressed the BB isoform of PDGF. All patients with elevated plasma levels of platelet derived growth factor had tumors which expressed the growth factor on immunohistochemical staining of tumor cells. Furthermore there was a significant correlation between plasma levels of platelet derived growth factor and the intensity of tissue staining. Patients with stage four breast cancer with tumors which were positive for platelet derived growth factor had a significantly lower response rate to chemotherapy as well as significantly shorter duration of survival. In addition, patients with stage four breast cancer who had elevated plasma PDGF levels had a significantly shorter survival. These results indicate that elevated plasma levels of platelet derived growth factor in patients with breast cancer are derived from the tumor cells and suggest that platelet derived growth factor may play a significant role in control tumor cell growth.

Plasma platelet-derived growth factor levels in coronary circulation in unstable angina pectoris

To examine whether plasma platelet-derived growth factor (PDGF) levels are elevated in the coronary circulation of patients with unstable angina, the plasma PDGF levels in the coronary sinus and aortic root were simultaneously examined in 14 patients with unstable angina, 15 with stable exertional angina, and 15 control subjects. The mean plasma PDGF level (pg/ml) in the coronary sinus was significantly higher (p < 0.01) in patients with unstable angina than in those with stable exertional angina and in control subjects (502.1 ± 98.7 vs 301.3 ± 62.5, and 312.7 ± 62.6). However, there were no significant differences in mean plasma PDGF levels in the aortic root among the 3 groups. It is concluded that PDGF release is increased in the coronary circulation in patients with unstable angina.

動脈硬化性疾患における血漿PDGF (血小板由来増殖因子)濃度と血小板活性化マーカーの変動

To determine the plasma level of the plateletderived growth factor (PDGF) and evaluate its significance, the plasma PDGF of 48 elderly patients with varying degrees of atherosclerosis was determined.According to brain CT findings, the ankle pressure index (API) and angiographic findings (cerebral/peripheral), the patients were divided into 3 groups with a differing degrees of atherosclerosis as follows; Group 1 (diffuse, severe) suffered from cortical cerebral infarction due to main trunk obstruction (A) and decreased API (<0.9)(B), Group II (focal, severe) suffered from either (A) or (B), and Group III (mild) did not suffer from either (A) or (B).Plasma PDGF concentrations were determined by RIA using the method described by Bannai. In addition, the β-thromboglobulin (β-TG), platelet factor 4 (PF4), 11-dehydrothromboxane B2 (11-DTXB2), and 6-keto-prostaglandin F1α (6-keto-PGF1α) levels were compared among all the groups, and to the levels found in young healthy controls.The mean PDGF level was 672±1105pg/ml, 220±132pg/ml, and 288±140pg/ml in group I (n=12), group II (n=20), and group III (n=16), respectively.This level did not significantly differ from one group to another, but was higher than the level found in the controls (163±47pg/m/: n=5).The mean β-TG, PF4, and 11-DTXB2 levels were also significantly elevated in these three groups compared with the controls, while the mean 6-keto-PGF1α level was lower, although this was not significant.PDGF revealed a positive correlation with PF4 and β-TG, and was especially strongly correlated with PF4 (r=0.6).These findings suggest that, as PF4 usually binds with endothelial cells soon after it is released from the platelets into the circulation, PDGF may also bind immediately to tissues near endothelial lesions.In conclusion, it appears that plasma PDGF levels do not always reflect the severity of a patient's atherosclerosis.

Plasma levels of platelet-derived growth factor in normal subjects and patients with ischemic heart disease

Plasma levels of platelet-derived growth factor (PDGF) were measured in 24 normal control subjects, 31 patients with stable angina pectoris, 25 patients with unstable angina pectoris, and 31 patients with acute myocardial infarction (AM) by a sensitive direct radioimmunoassay. The plasma PDGF level in normal control subjects was 273 ± 25 pg/ml; there was no significant correlation between the plasma PDGF level and age. Plasma PDGF levels in patients with unstable angina pectoris and acute myocardial infarction were significantly lower than those in normal control subjects and patients with stable angina pectoris ( p < 0.05). In patients with acute myocardial infarction the plasma PDGF level in the chronic phase was significantly higher than that in the acute phase ( p < 0.05). These observations raise the possibility that PDGF is involved in the pathophysiology of ischemic heart disease.