Toll-like receptor-4 is upregulated in plaque debris of patients with acute coronary syndrome more than Toll-like receptor-2.

Atherosclerosis is a disease characterized by inflammation in the arterial wall. Atherogenesis is dependent on the innate immune response involving activation of Toll-like receptors (TLRs) and the expression of inflammatory proteins, those may lead to acute coronary syndrome (ACS). We investigated the expression level of TLR-4 in ACS, as compared with TLR-2 and patients with stable angina. Fifty-eight consecutive patients who underwent primary percutaneous coronary intervention (PCI, n = 29) because of ACS and elective PCI (n = 29) because of stable angina using a filter-device distal protection device system were prospectively analyzed. mRNA levels of TLR-2 and TLR-4 in debris containing various inflammatory tissues entrapped in the filter device were altogether analyzed using real-time PCR. There were no significant differences in age, sex distribution, between stable angina and ACS groups. TLR-4 expression levels were higher in patients with ACS than in patients with stable angina. TLR-4 might play a more important role than TLR-2 in atherogenesis, especially in ACS.

Gender differences in factors influencing electrocardiographic findings of left ventricular hypertrophy in severe aortic stenosis.

We investigated gender differences in factors influencing the electrocardiographic (ECG) findings of left ventricular hypertrophy (LVH) in patients with severe aortic stenosis (AS). The functional and geometric responses of the left ventricle to chronic pressure overload, such as hypertension and AS, have been reported to be different between men and women. However, gender differences in the factors influencing the ECG findings of LVH in pressure overload remain unknown. We conducted a retrospective observational study in consecutive patients with severe AS (aortic valve area (AVA) assessed by cardiac catheterization <1.0 cm(2)) without concomitant significant aortic regurgitation, mitral stenosis and/or regurgitation, conduction disturbance, or myocardial infarction (n = 35 males, 68 females). The ECG criteria were classified into three categories: (1) high voltage by the Sokolow-Lyon index associated with ST-T wave changes (with no digitalis therapy); (2) high voltage alone; and (3) normal. Groups 1 and 2 were defined as LVH on ECG. We compared the ECG findings in relation to the AS severity between genders. Women were older, but there were no significant differences in the prevalence of hypertension, AVA index (AVAI), mean pressure gradient or peak velocity across the AV, LV mass index (LVMI) derived from echocardiography or the distribution of ECG categories between genders. A multiple logistic regression analysis including age, gender, hypertension, AVAI, mean pressure gradient, and LVMI revealed that the LVMI (P = 0.001) and AVAI (P = 0.0434) were significantly related to the distribution of ECG categories. LVMI significantly predicted LVH on ECG in both genders, but AVAI was a predictive factor in only women. ECG LVH in patients with severe AS may be mainly reflected by LVMI in men and by both LVMI and AVAI in women. Factors other than AVA, such as end-stage disease and/or complicating factors such as hypertension, may underlie the observed differences in ECG findings of LVH between men and women.

Acute lower-extremity arterial thrombosis with immune thrombocytopenia.

We describe an acute lower-extremity arterial occlusion in a 30-year-old woman with immune thrombocytopenia and polycystic ovary syndrome. Thrombosis may be a complication of immune thrombocytopenia requiring careful management.

A case of giant left main coronary artery aneurysm in an elderly man.

Aneurysms of the left main coronary artery are rare and their optimal treatments remain unknown. A 64-year-old man without any symptoms was referred to our department for suspected coronary aneurysm. Transthoracic echocardiography demonstrated an aneurysm of the left main coronary artery. On transesophageal echocardiography, the thrombus was suspected inside and severe ostial stenosis of the left coronary artery was highly suspected due to the accelerated flow velocity. Multidetector computed tomography demonstrated the aneurysm as being 37 mm in diameter with significant stenosis at both left coronary arteries, more clearly than coronary angiography. Because of its size and coexisting coronary artery disease, surgical closure of the aneurysm and coronary artery bypasses were performed. Echocardiography and coronary computed tomography could help in the diagnosis and the therapeutic decision in the case of left main coronary artery aneurysm before coronary angiography.

Recurrence of pulmonary embolism in young man with retroperitoneal tumor despite insertion of temporary IVC filter.

Pulmonary embolism (PE) is a fatal disease that is very rare in young people. A 21-year-old man developed PE because of a retroperitoneal tumor. The inferior vena cava (IVC) was obstructed by the tumor, and thrombus existed in the right common iliac vein. Thrombolysis and heparinization improved his symptoms prior to urgent tumor resection. A temporary IVC filter was inserted the day before the operation, but 8 h later fatal massive PE occurred. At autopsy, the retroperitoneal tumor was revealed as a metastatic choriocarcinoma. Prophylactic use of a temporary IVC filter might have paradoxically induced recurrence of massive PE in this case.

Lysophosphatidylcholine activates extracellular signal-regulated kinases 1/2 through reactive oxygen species in rat vascular smooth muscle cells.

Lysophosphatidylcholine (lysoPC) acts on vascular smooth muscle cells (VSMCs) to produce a mitogenic response through the activation of extracellular signal-regulated kinases 1/2 (ERK1/2). In the present study, we examined the importance of reactive oxygen species (ROS) in lysoPC-stimulated ERK1/2 activation in cultured rat VSMCs. Treatment with lysoPC for 3 minutes caused a 2-fold increase in intracellular ROS that was blocked by the NADH/NADPH oxidase inhibitor, diphenylene iodonium (DPI). Antioxidants, N-acetyl-L-cysteine, glutathione monoester, or alpha -tocopherol, inhibited ERK1/2 activation by lysoPC. Almost identical results were obtained in the VSMC line A10. Pretreatment of VSMCs with DPI but not allopurinol or potassium cyanide (KCN) abrogated the activation of ERK1/2. The Flag-tagged p47phox expressed in A10 cells was translocated from the cytosol to the membrane after 2 minutes of stimulation with lysoPC. The overexpression of dominant-negative p47phox in A10 cells suppressed lysoPC-induced ERK activation. The ROS-dependent ERK activation by lysoPC seems to involve protein kinase C- and Ras-dependent raf-1 activation. Induction of c-fos expression and enhanced AP-1 binding activity by lysoPC were also inhibited by DPI and NAC. Taken together, these data suggest that ROS generated by NADH/NADPH oxidase contribute to lysoPC-induced activation of ERK1/2 and subsequent growth promotion in VSMCs.

Clinical impact of coronary artery spasm in patients with no significant coronary stenosis who are experiencing acute coronary syndrome.

BACKGROUND AND OBJECTIVE: To clarify the clinical features of coronary artery spasm (CAS) with no significant coronary stenosis in patients with suspected acute coronary syndrome (ACS) in real practice. METHODS: This is a retrospective observational study of patients with suspected ACS (n=645) based on symptoms, electrocardiographic changes, and/or positive cardiac biomarkers and vasospastic angina (VSA, n=90). ACS patients were divided into two groups: (1) organic ACS (n=515), culprit lesion ≥75% coronary stenosis with/without thrombosis; (2) spastic ACS (n=70), coronary stenosis <75%, either with positive acetylcholine (ACh) test (n=51) or without ACh test but verified spontaneous spasm (n=19). The study compared clinical characteristics among organic ACS, spastic ACS, and VSA. RESULTS: One hundred and thirty suspected ACS patients had a coronary organic stenosis <75% (130/645, 20%). Seventy of those patients (70/130, 54%) were confirmed to have CAS, and these accounted for 11% of all ACS patients (70/645). The rate of cigarette smoking was highest in the spastic ACS. No spastic ACS patients died during their hospital stay or after discharge, whereas acute myocardial infarction occurred in 19%, aborted sudden cardiac death in 6%, multivessel spasm was provoked in 78%, and diffuse spasm was more frequently provoked than in the VSA group (82% vs. 62%). CONCLUSIONS: CAS is not a rare cause of ACS. Although the prognosis of spastic ACS is good, there are occasional critical cases. An initial differential diagnosis including an ACh test is thus important to decide the treatment strategy of ACS.

Comparison of the reperfusion efficacy of thrombus aspiration with and without distal protection during primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction.

We evaluated a hypothesis that thrombus aspiration with distal protection is superior to simple thrombus aspiration in patients treated with primary percutaneous coronary intervention (PCI). A total of 176 consecutive patients with ST-segment elevation myocardial infarction were enrolled in this study and assigned to either the thrombus aspiration group (A, n = 104) or the thrombus aspiration with distal protection group using a filter device system (A + DP, n = 72). We compared the angiographic reperfusion grade, left ventricular (LV) function, and clinical outcomes between the 2 groups. There were no significant differences in age, gender distribution, the onset-to-reperfusion time, the peak levels of creatine kinase, or 6-month mortality between the 2 groups. The rate of achieving a Thrombolysis In Myocardial Infarction flow grade of 3 and a myocardial blush grade of 3 was higher in the A + DP group than in the A group. Among the patients who underwent follow-up catheterization 6 months after PCI (A, n = 62; A + DP, n = 52), there were no significant differences in the LV end-diastolic volume index, LV end-systolic volume index, or LV ejection fraction between the 2 groups at the time of PCI or 6 months after PCI. In conclusion, thrombus aspiration with distal protection may be more effective in initially restoring the coronary blood flow than thrombus aspiration alone, although it may not be superior to thrombus aspiration in preventing LV remodeling or preserving the LV function in patients with ST-segment elevation myocardial infarction.

Relationships between inflammatory mediators and coronary plaque composition in patients with stable angina investigated by ultrasound radiofrequency data analysis.

Inflammation has been recognized as a critical process in the progression of coronary atherosclerosis. Virtual Histology-intravascular ultrasound (VH-IVUS) has been reported to be a useful tool for tissue characterization of coronary atherosclerotic plaque. We investigated relationships between plaque composition and inflammation-related factors possibly contributing to atheromatous plaque formation and progression, since these are largely unknown. Using VH-IVUS, we measured plaque volume and composition at the culprit lesions in patients with stable angina undergoing elective percutaneous coronary intervention (n = 33, 39 de novo lesions), and then analyzed correlations between plaque components and serum levels of inflammatory factors in both aorta and culprit coronary artery obtained by aspiration using a distal protection device. Linear regression analysis revealed that both aortic and coronary LDL cholesterol levels correlated with %plaque burden along the culprit lesions (r = 0.535 and 0.539, respectively), but with none of the plaque components. Of %plaque components, fibro-fatty (FF) correlated positively with both aortic and coronary T cell/B cell ratios (r = 0.335 and 0.359, respectively) whereas necrotic core (NC) correlated negatively with both aortic and coronary T cell/B cell ratios (r = -0.373 and -0.483, respectively). These results suggest that LDL cholesterol may be a good marker for total coronary plaque volume whereas the lymphocyte subset of T cell/B cell ratios may be a good marker for plaque composition, especially FF and NC components volume.