Downregulation of the hemoglobin scavenger receptor in individuals with diabetes and the Hp 2-2 genotype implications for the response to intraplaque hemorrhage and plaque vulnerability
Downregulation of the hemoglobin scavenger receptor in individuals with diabetes and the Hp 2-2 genotype implications for the response to intraplaque hemorrhage and plaque vulnerability
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DOI：
10.1161/circresaha.107.149435
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发表时间：
2007-07-06
影响因子：
20.1
通讯作者：
Moreno, Pedro R.
中科院分区：
文献类型：
--
作者：
Levy, Andrew P.;Purushothaman, K. Raman;Moreno, Pedro R.
在糖尿病（DM）患者中，结合珠蛋白（Hp）基因型是心肌梗死易感性的主要决定因素。我们认为这是因为糖尿病和幽门螺杆菌基因型依赖性的斑块内出血反应的差异。巨噬细胞血红蛋白清除受体CD 163在斑块内出血后从溶解的红细胞释放的血红蛋白的清除中起重要作用。我们试图检验CD 163的表达是DM和Hp基因型依赖性的假设。通过免疫组织化学定量斑块中的CD 163，通过FACS定量外周血单核细胞（PBMC）上的CD 163，并通过ELISA定量血浆中的可溶性CD 163（sCD 163）。在DM斑块中，尽管巨噬细胞浸润增加，但CD 163免疫反应性较低，导致表达CD 163的巨噬细胞百分比显著降低（27 +/- 2% vs 70 +/-2%，P = 0.0001）。与非DM个体相比，DM个体中表达CD 163的PBM百分比降低（3.7 +/- 0.6%对7.1 +/-0.9%，P < 0.002），而可溶性血浆CD 163增加（2.6 +/- 1.1 μ g/ mL对1.6 +/- 0.8 μ g/mL，P < 0.0005）。在糖尿病患者中，Hp 2- 2基因型与表达CD 163的PBM百分比降低（2.3 +/- 0.5%对5.6 +/-1.3%，P = 0.01）和血浆可溶性CD 163增加（3.0 +/- 0.2 μ g/ mL对2.3 +/-0.2 μ g/ mL，P = 0.04）相关。综上所述，这些结果表明，受损的血红蛋白清除能力在Hp 2- 2糖尿病个体，并可能提供关键的洞察力，解释心肌梗死的发病率在这一人群中增加。
In individuals with diabetes mellitus ( DM), the haptoglobin ( Hp) genotype is a major determinant of susceptibility to myocardial infarction. We have proposed that this is because of DM and Hp genotype - dependent differences in the response to intraplaque hemorrhage. The macrophage hemoglobin scavenging receptor CD163 plays an essential role in the clearance of hemoglobin released from lysed red blood cells after intraplaque hemorrhage. We sought to test the hypothesis that expression of CD163 is DM and Hp genotype - dependent. CD163 was quantified in plaques by immunohistochemistry, on peripheral blood monocytes ( PBMs) by FACS, and as soluble CD163 ( sCD163) in plasma by ELISA. In DM plaques, despite an increase in macrophage infiltration, CD163 immunoreactivity was lower, resulting in a dramatic reduction in the percentage of macrophages expressing CD163 ( 27 +/- 2% versus 70 +/- 2%, P = 0.0001). In individuals with DM as compared with individuals without DM, the percentage of PBMs expressing CD163 was reduced ( 3.7 +/- 0.6% versus 7.1 +/- 0.9%, P < 0.002) whereas soluble plasma CD163 was increased ( 2.6 +/- 1.1 mu g/ mL versus 1.6 +/- 0.8 mu g/mL, P < 0.0005). Among DM individuals, the Hp 2- 2 genotype was associated with a decrease in the percentage of PBMs expressing CD163 ( 2.3 +/- 0.5% versus 5.6 +/- 1.3%, P = 0.01) and an increase in plasma soluble CD163 ( 3.0 +/- 0.2 mu g/ mL versus 2.3 +/- 0.2 mu g/ mL, P = 0.04). Taken together, these results demonstrate an impaired hemoglobin clearance capacity in Hp 2- 2 DM individuals and may provide the key insight explaining the increased incidence of myocardial infarction in this population.