心力衰竭患者与心脏β_2、α_1肾上腺素能受体和血管紧张素Ⅱ1型受体的自身抗体

Study of autoantibodies against G-protein-coupled β_2-and α_1-adrenergic and angiotensinⅡ-1 receptors in patients with chronic heart failure

目的 本研究检测不同心脏病所致的慢性心力衰竭 (心衰 )患者 β2 、α1 肾上腺素能受体和血管紧张素Ⅱ 1型 (AT1 )受体的自身抗体 ,探讨心功能发生病理变化时 ,上述三种自身抗体的产生与疾病的相关性。方法 以细胞外第二环表位肽段的合成肽作为抗原 ,应用酶联免疫吸附测定(ELISA)技术 ,随机检测 2 67例受试者血清中 β2 、α1 和AT1 受体的自身抗体。心衰组为 2 0 6例不同心脏病的心衰患者 ,其中缺血性心肌病 63例、扩张型心肌病 86例、高血压病 57例。正常组为 61例正常人作对照。结果 (1 )心衰组 β2 、α1 和AT1 受体的自身抗体阳性分别为 46 1 % (95/ 2 0 6)、48 5 % (1 0 0 /2 0 6)和 46 6 % (96/ 2 0 6) ,明显高于正常组的 8 2 % (5/ 61 )、9 8% (6/ 61 )和 1 3 1 % (8/ 61 ) ,P <0 0 1 ;(2 )心衰组自身抗体阳性患者的抗体滴度分别为 1∶89、1∶98和 1∶96 ,明显高于正常组的 1∶35、1∶32和 1∶31 ,P <0 0 1 ;(3)心衰组 β2 受体自身抗体阳性者 95例中 ,有 60例 (63 2 % )患者同时具有α1 受体的自身抗体 ,有 64例 (67 4% )患者同时具有AT1 受体的自身抗体 ,有 51例 (53 7% )的患者同时具有上述三种受体的自身抗体阳性。结论 β2 、α1 和AT1

Objective To determine whether autoantibodies against the cardiac G protein coupled β 2 and α 1 adrenergic and angiotensinⅡ 1(AT 1) cardiovascular receptors are related to chronic heart failure (CHF) caused by different heart diseases Methods Three synthetic peptides β 2 , α 1 adrenoceptors and AT 1 receptors, which corresponded to amino acids sequences of the second extracellular loop of human, were used as antigens in an SA ELISA to screen sera from 267 subjects Among them 206 had CHF caused by different heart diseases, of whom 63 were ischemic cardiomyopathy, 86 were idiopathic dilated cardiomyopathy, 57 were hypertension disease The remaining 61 healthy donors were in control group (NC) Results (1) The positive sera for β 2 and α 1 adrenoceptor and AT 1 receptors in CHF group were 46 1%(95/206), 48 5%(100/206) and 46 6%(96/206), respectively, significantly higher than those of 8 2% (5/61), 9 8%(6/61) and 13 1% (18/61) ( P <0 01) in NC (2) The geometric mean titers of autoantibodies against β 2 and α 1 adrenergic and AT 1 receptors in patients with CHF were 1∶89, 1∶98 and 1∶96, respectively, substantially higher than those of 1∶35, 1∶32, 1∶31 ( P <0 01)in NC (3) In the CHF group, 63 2%(60/95)of the patients with autoantibodies against β 2 adrenergic receptors had autoantibodies against α 1 adrenergic receptors, and 67 4%(64/95)of patients with autoantibodies against β 2 adrenergic receptors had autoantibodies against AT 1 receptors The frequency of the three receptors autoantibodies in patients with CHF was 53 7%(51/95) Conclusions Our study indicates that autoantibodies against the cardiac G protein coupled β 2 adrenergic, α 1 adrenergic and AT 1 receptors exist in sera from heart failure patients with different heart diseases We speculate that the three autoantibodies against the cardiac G protein coupled receptors can be detected not only in the sera of CHF patients with dilated cardiomyopathy, but also in CHF patients with ischemic cardiomyopathy and hypertension We conclude that autoantibodies against the cardiac G protein coupled β 2 adrenergic, α 1 adrenergic and AT 1 receptors may be all related to cardiac structural andfunctional changes in the primary heart disease Each autoantibody, which resists the above three receptors, may play an important role in the pathogenesis and myocardial remodeling of heart failure with different heart diseases