Establishment of a high sensitivity plasma assay for human pentraxin3 as a marker for unstable angina pectoris.

OBJECTIVE: Plasma pentraxin 3 (PTX3) levels are increased in patients with acute myocardial infarction, yet its involvement in unstable angina pectoris (UAP) remains unclear. To critically evaluate the role of PTX3 in UAP, a sensitive and precise measurement of PTX3 concentration is needed. METHODS AND RESULTS: We established a high sensitive plasma ELISA assay system for the detection of PTX3 using monoclonal antibodies. The lower limit of detection of our ELISA was 0.1 ng/mL, sensitivity far greater than the current commercially available kit. Plasma samples were obtained from 162 consecutive patients treated for hypertension, hyperlipidemia, diabetes mellitus, or cardiovascular disease at a physician's office. PTX3 was not associated with any known coronary risk factors. Additionally, we collected plasma samples from 252 consecutive subjects admitted to a university hospital for coronary artery assessment by coronary angiography. PTX3 was significantly increased in patients in whom coronary intervention was performed. We further analyzed the plasma level of PTX3 in 52 patients with effort angina (EAP) and 16 patients with UAP. Compared with the control group, PTX3 were significantly higher in the UAP group. CONCLUSIONS: The levels of plasma PTX3 were increased in patients with arterial inflammation, especially UAP. This PTX3 detection system will be useful for the prediction of UAP.

Blunted reduction of pulse pressure during nighttime is associated with left ventricular hypertrophy in elderly hypertensive patients.

Increased pulse pressure (PP) is recognized as a risk factor for cardiovascular disease, especially in elderly patients. However, blood pressure (BP) is known to have a circadian variation. Therefore, this study asked whether or not PP has a circadian variation and, if so, whether a circadian variation of PP has clinical importance. Ambulatory BP monitoring (every 30 min for 48 h) was performed in 255 patients with untreated essential hypertension (24 to 82 years old; mean: 52+/-12 years). Left ventricular mass index (LVMI) was estimated from M-mode echocardiography. PP was decreased during nighttime (10+/-11% reduction from daytime PP). Multivariate linear regression analysis showed that, among four variables-the degree of nighttime PP reduction, daytime PP, 48-h systolic BP, and nondipper hypertension-the degree of nighttime PP reduction had the strongest (inverse) correlation with LVMI in a subgroup of elderly patients (> or =60 years old, n =67) (standardized regression coefficient=-0.32, p =0.02), whereas this association was not significant in the whole patient population unclassified by age. Furthermore, a blunted reduction of nighttime PP in combination with nondipper hypertension was an incremental risk for increase in LVMI in the elderly patients. In conclusion, PP is reduced during nighttime, but the degree of reduction varies among patients. The blunted reduction of nighttime PP is a risk for left ventricular hypertrophy, an established predictor of hypertension-induced cardiovascular events, and it may thus play a role in cardiovascular complications, especially in elderly patients with nondipper hypertension.

Soluble fibrin augments spreading of fibroblasts by providing RGD sequences of fibrinogen in soluble fibrin.

We previously reported that fibroblasts were found to spread far more avidly on NaBr-solubilized fibrin monomer (FM) monolayers than on immobilized fibrinogen (Fbg), indicating that removal of fibrinopeptides by thrombin is a prerequisite for the fibrin-mediated augmentation of cell spreading [J. Biol. Chem. 272 (1997) 8824-8829]. Soluble fibrin (SF), a 1:2 complex of fibrin-monomer and fibrinogen, is known to be present in the circulating blood under the pathological condition in which blood coagulation is activated. However, its physiological roles are still incompletely known. Fibroblasts spread on immobilized purified soluble fibrin. Cells spreading on immobilized soluble fibrin were blocked by the exogenous addition of soluble fibrin and glycine-arginine-glycine-aspartic acid-serine-phenylalanine (GRGDSP)-synthetic peptide but not by the addition of fibrinogen or fibrin monomer. However, cell spreading activity was decreased in the surfaces coated with fragment X, whose Aalpha-chains lack carboxyl-terminal segments including arginine-glycine-aspartic acid (RGD)-2 domain, fibrin monomer complexes. It suggests that the RGD-2 domain of fibrinogen after being complexed with fibrin monomer plays a pivotal role for soluble fibrin-dependent cell spreading. Soluble fibrin in plasma derived from the patients of disseminated intravascular coagulation (DIC) was immuno-purified using the monoclonal antibody (mAb) which specifically recognizes the Ca(++)-dependent conformer of fibrinogen. The purified soluble fibrin consisted of desAA-fibrin monomer and two fibrinogen molecules and did show the cell spreading activity. Thus, soluble fibrin in plasma plays a role as the modulator of thrombogenic process in vivo.

SP-D as a marker of amiodarone-induced pulmonary toxicity.

Two patients with amiodarone-induced pulmonary toxicity (APT) showed abnormally increased serum SP-D concentrations, although their KL-6 level was within the normal range. In a 59-year-old man with ischemic heart disease, APT progressed rapidly and required steroid pulse therapy. During the clinical course, SP-D was as high as 375 ng/ml, although the KL-6 level was only 289 U/ml. In a 58-year-old man treated for dilated cardiomyopathy, SP-D increased to 289 ng/ml, while KL-6 remained at less than 500 U/ml. These cases indicate that SP-D is a useful and early diagnostic marker for APT even when KL-6 is not elevated.

Restored atrial excitability after late recanalization in a patient with atrial standstill and acute myocardial infarction.

Atrial standstill is electrophysiologically characterized by the loss of spontaneous excitation in atrial muscle and the inability to cause action potential firing upon electrical stimulation. Clinical diagnosis of transient standstill of the right atrium was made in a patient with acute occlusion of the right coronary artery and acute renal failure. Percutaneous coronary intervention, performed 5 days after the onset, restored the coronary blood flow and resulted in full recovery of electrical activity and regular sinus rhythm.