AT1拮抗剂与血管紧张素转换酶抑制剂对冠心病患者炎症标志物和血小板聚集的比较作用
Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease.
作者信息
Schieffer Bernhard, Bünte Christoph, Witte Jana, Hoeper Kirsten, Böger Rainer H, Schwedhelm Edzard, Drexler Helmut
机构信息
Department of Cardiology and Angiology, Medizinische Hochschule Hannover, Germany.
出版信息
J Am Coll Cardiol. 2004 Jul 21;44(2):362-8. doi: 10.1016/j.jacc.2004.03.065.
OBJECTIVES
We evaluated whether renin-angiotensin system (RAS) blockade attenuates cardiovascular events.
BACKGROUND
Because inflammation and enhanced thrombogenesis are hallmarks of atherosclerosis, we assessed whether RAS inhibition elicits anti-inflammatory and anti-aggregatory effects.
METHODS
Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), metalloprotease 9 (MMP-9), and interleukin 10 (IL-10) were determined in patients with coronary artery disease (CAD) and arterial hypertension six to eight weeks after coronary angioplasty (low-density lipoprotein serum levels <150 mg/dl). Patients were randomized double-blind to either 20 mg enalapril (ENAL, n = 27) or 300 mg irbesartan (IRB, n = 21) for 3 months. Blood samples were drawn at baseline and at three months. Thromboxane A2-induced platelet aggregation was determined turbidimetrically; urine bicyclo-prostaglandin E2 (PGE(2)) and inflammatory markers were measured by enzyme-linked immunosorbent assay technique.
RESULTS
Both treatment regimens enhanced serum IL-10 levels (IRB p < 0.001, ENAL p < 0.03) and reduced serum MMP-9 protein (IRB p < 0.001, ENAL p < 0.05) and MMP-9 activity (IRB p < 0.005, ENAL p < 0.05). Only IRB reduced serum IL-6 and hsCRP levels significantly compared with baseline (p < 0.01), whereas ENAL did not (hsCRP p < 0.02 IRB vs. ENAL, p < 0.01 IRB vs. ENAL). Platelet aggregation was only reduced by IRB (p < 0.001, ENAL p < 0.06, IRB vs. ENAL p < 0.001) while urine PGE(2) levels remained unchanged.
CONCLUSIONS
Angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor (AT1) blockade reduced serum MMP-9 protein/activity to a similar extent, and only AT1 blockade reduced hsCRP, IL-6, and platelet aggregation in patients with CAD. Thus, AT1-blockade appears to exert stronger systemic anti-inflammatory and anti-aggregatory effects compared with ACE inhibition.
目的
我们评估了肾素-血管紧张素系统（RAS）阻断是否能减轻心血管事件。
背景
由于炎症和血栓形成增强是动脉粥样硬化的特征，我们评估了RAS抑制是否具有抗炎和抗聚集作用。
方法
在冠状动脉成形术后六至八周（低密度脂蛋白血清水平<150mg/dl），对患有冠状动脉疾病（CAD）和动脉高血压的患者测定白细胞介素6（IL-6）、高敏C反应蛋白（hsCRP）、金属蛋白酶9（MMP-9）和白细胞介素10（IL-10）。患者被随机双盲分为服用20mg依那普利（ENAL，n = 27）或300mg厄贝沙坦（IRB，n = 21），为期3个月。在基线和三个月时采集血样。通过比浊法测定血栓素A2诱导的血小板聚集；通过酶联免疫吸附测定技术测量尿双环前列腺素E2（PGE(2)）和炎症标志物。
结果
两种治疗方案均提高了血清IL-10水平（IRB p<0.001，ENAL p<0.03），并降低了血清MMP-9蛋白（IRB p<0.001，ENAL p<0.05）和MMP-9活性（IRB p<0.005，ENAL p<0.05）。与基线相比，只有IRB显著降低了血清IL-6和hsCRP水平（p<0.01），而ENAL没有（hsCRP p<0.02 IRB与ENAL相比，p<0.01 IRB与ENAL相比）。只有IRB降低了血小板聚集（p<0.001，ENAL p<0.06，IRB与ENAL相比p<0.001），而尿PGE(2)水平保持不变。
结论
血管紧张素转换酶（ACE）抑制和血管紧张素II 1型受体（AT1）阻断在相似程度上降低了血清MMP-9蛋白/活性，并且只有AT1阻断降低了CAD患者的hsCRP、IL-6和血小板聚集。因此，与ACE抑制相比，AT1阻断似乎具有更强的全身抗炎和抗聚集作用。
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