Atherosclerosis and acute coronary syndromes.

In the past 20 years, there has been much new knowledge discovered on the pathogenesis of atherosclerosis and complicated and vulnerable plaques leading to a better understanding of acute coronary syndromes (ACS). The role of thrombosis, lipid metabolism, and inflammation has been investigated at the cellular and molecular levels, resulting in important new diagnostic and therapeutic strategies. The characterization of the role of hemodynamic shear stress and its regulation of cytoskeletal function in endothelial repair and the discovery of endothelial precursor cells (EPCs) derived from the bone marrow have provided new insight into vascular repair. Thus, our knowledge continues to increase, leading to improved prevention, diagnosis, and treatment of ACS.     

Complement activation in acute coronary syndromes

The complement system is part of the host defence response. However, considerable evidence suggests that complement plays an important role in the pathophysiology of ischemic heart disease. The aim of this study was to evaluate complement activation in patients with all forms of acute coronary syndromes (ACS) and to examine the relationship between the degree of complement activation and myocardial injury. The study population included 152 subjects (26 females): 82 with ACS (35 acute myocardial infarction (AMI), 22 non-Q wave MI (NQMI), 25 unstable angina (UAP)) (Group A), 35 stable angina (SA) (Group B), and 35 healty control subjects (Group C). Complement 3 (C3), Complement 4 (C4), C-reactive protein (CRP), troponin I (TnI) as well as creatine kinase MB (CK-MB) were evaluated. Patients' blood samples were taken on admission (day 1) and after 2, 3 and 7 days in group A. However, only one measurement was performed in the groups B and C. Plasma C3 and C4 peak levels were significantly higher in patients with AMI (141+/-29 and 35+/-11 mg/dl) and NQMI (136+/-13 and 35+/-7 mg/dl) than in patients with SA (128+/-14 and 27+/-10 mg/dl) and the control subjects (114+/-22 and 22+/-7 mg/dl) (p<0.03). Also, C3 and C4 serum levels in patients with SA and UAP (126+/-16 and 31+/-7 mg/dl) were significantly higher than those in control subjects (p<0.01, p<0.03, respectively). At 1-week follow-up, there were no significant differences between the plasma levels of C3 and C4 in patients with UAP (p>0.05). However, plasma levels of C3 and C4 were significantly different between days in patients with AMI and NQMI (p<0.0001). Plasma C3 and C4 levels in ACS showed a relationship with peak CK-MB and Tn I levels (p<0.01). Plasma CRP level in ACS showed positive correlation with C3 (p<0.01) and C4 (p<0.001). In this study, we determined that plasma C3 and C4 levels were elevated in ACS and SA. Although C3 and C4 were higher in ACS and SA, the systemic levels of inflammatory markers in patients with SA and UAP were lower than those found in the AMI and NQMI groups. The relationship between C3, C4 levels and ACS further suggests that the complement activation is related to necrosis within the myocardium.     

急性冠脉综合症与补体激活

目的： 评价各种类型急性冠脉综合症 (ACS) 病人补体激活的情况和补体激活与心肌损伤的关系。方法： 研究对象分为ACS组110例和正常对照组18人。 ACS组包括ST段抬高型心肌梗死（STEMI）51例，非ST段抬高型心肌梗死（NSTEMI）28例和不稳定性心绞痛（UA）31人。检测病人和正常对照健康人血浆C₃和C₄，CK-MB和肌钙蛋白T (TnT)浓度。结果： STEMI和 NSTEMI病人峰值C₃ 水平［分别为（1 525±302） mg/L和（1 516±289）mg/L］ 和C₄［分别为（423±123） mg/L和（396±68） mg/L］水平高于UA病人和对照组的C₃［分别为（1 275±172） mg/L和（1 072±196） mg/L,P<0.01］ 和C₄［分别为（356±91）mg/L和（182±73） mg/L,P<0.01］。UA病人的 C₃ ［(1 275±172） mg/L］和C₄ ［（356±91） mg/L］均高于对照组（P<0.01）。 ACS病人C₃和C₄水平在住院的前7 d均有明显的变化（P<0.01）。ACS病人峰值C₃和C₄水平与峰值CK-MB（分别为r=0.51和r=0.46，P<0.01）和肌钙蛋白T（分别为r=0.48和r=0.39，P<0.01）呈正相关。结论： ACS病人血浆C₃和C₄均明显升高。C₃和C₄水平与ACS的联系提示补体激活与心肌坏死有关。     

Delay of neutrophil apoptosis in acute coronary syndromes

Apoptosis of polymorphonuclear neutrophils (PMN) is currently discussed as a key event in the control of inflammation. This study determined PMN apoptosis and its underlying mechanisms in controls (C), patients with stable (SAP) or unstable angina (UAP), and with acute myocardial infarction (AMI). Blood was drawn from 15 subjects of each C, SAP, UAP, and AMI. Apoptosis was measured by flow cytometry in isolated PMN (propidium iodide staining) and PMN from whole blood (CD16, FcgammaRIII). Serum cytokines were determined by enzyme-linked immunosorbent assay. Apoptosis of isolated PMN was delayed significantly in acute coronary syndromes (ACS) as compared with SAP or C (C, 51.2+/-12.6%; SAP, 44.9+/-13.6%; UAP, 28.4+/-10.1%; AMI, 20.3+/-8.5%; AMI or UAP vs. SAP or C, P<0.001). These results were confirmed by measurement of PMN apoptosis in cultured whole blood from patients and controls. Moreover, serum of patients with ACS markedly reduced apoptosis of PMN from healthy donors. Analysis of patients' sera revealed significantly elevated concentrations of tumor necrosis factor alpha, interferon-gamma (IFN-gamma), granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin (IL)-1beta in ACS (vs. C and SAP). IFN-gamma, GM-CSF, and IL-1beta significantly delayed PMN apoptosis in vitro. Furthermore, coincubation of PMN with adenosine 5'-diphosphate-activated platelets significantly inhibited PMN apoptosis as compared with coculture with unstimulated platelets. This study demonstrates a pronounced delay of PMN apoptosis in UAP and AMI, which may result from increased serum levels of IFN-gamma, GM-CSF, and IL-1beta and from enhanced platelet activation. Therapeutical modulation of these determinants of PMN lifespan may provide a new concept for the control of inflammation in ACS.     

Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty.

In percutaneous transluminal coronary angioplasty, a catheter system is introduced through a systemic artery under local anesthesia to dilate a stenotic artery by controlled inflation of a distensible balloon. Over the past 18 months, we have used this technic in 50 patients. The technic was successful in 32 patients, reducing the stenosis from a mean of 84 to 34 per cent (P less than 0.001) and the coronary-pressure gradient from a mean of 58 to 19 mm Hg (P less than 0.001). Twenty-nine patients showed improvement in cardiac function during follow-up examination. Because of acute deterioration in clinical status, emergency bypass was later necessary in five patients; three showed electrocardiographic evidence of infarcts. Patients with single-vessel disease appear to be most suitable for the procedure, and a short history of pain indicates the presence of a soft (distensible) atheroma likely to respond to dilatation. We estimate that only about 10 to 15 per cent of candidates for bypass surgery have lesions suitable for this procedure. A prospective randomized trial will be necessary to evaluate its usefulness in comparison with surgical and medical management.