Objectives: Bone morphogenetic protein-4 (BMP4) has been proved to be an important regulatory factor for the pathological process of atherosclerosis (AS). However, there are few related clinical studies. This study aims to investigate the levels of plasma BMP4 in patients suffering from the arterial occlusive diseases (ACD) characterized by AS, and further to test the relationship between BMP4 and inflammation and vascular injury.
Methods: A total of 38 ACD patients (the ACD group) and 38 healthy people for the physical examination (the control group) were enrolled. The plasma in each subject from both groups was obtained to test the levels of BMP4, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-10, and vascular endothelial cadherin (VE-cadherin), and the relationship between BMP4 and the detected indicators above were further analyzed.
Results: Compared with the control group, the patients in the ACD group displayed significant elevations in the neutrophil to lymphocyte ratio [NLR, 1.63 (1.26, 1.91) vs 3.43 (2.16, 6.61)] and platelet to lymphocyte ratio [PLR, 6.37 (5.26, 7.74) vs 15.79 (7.97, 20.53)], while decrease in the lymphocyte to monocyte ratio [LMR, 5.67 (4.41, 7.14) vs 3.43 (2.07, 3.74)] (all P<0.05). Besides, the ACD patients displayed significant elevations in plasma BMP4 [581.26 (389.85, 735.64) pg/mL vs 653.97(510.95, 890.43) pg/mL], TNF-α [254.16 (182.96, 340.70) pg/mL vs 293.29(238.90, 383.44) pg/mL], and VE-cadherin [1.54 (1.08, 2.13) ng/mL vs 1.85 (1.30, 2.54) ng/mL], and decrease in IL-10 [175.89 (118.39, 219.25) pg/mL vs 135.92 (95.80, 178.04) pg/mL] (all P<0.05). While the levels of IL-1β remained statistically comparable between the 2 groups (P=0.09). Furthermore, the plasma BMP4 levels were further revealed to be positively correlated with the levels of IL-1β (r=0.35), TNF-α (r=0.31) and VE-cadherin (r=0.47), while they were negatively correlated with the levels of IL-10 (r=-0.37; all P<0.01).
Conclusions: After ACD occurrence, the patients' plasma concentrations of BMP4 would be upregulated, which may serve as a candidate to indicate the levels of inflammation and vascular injury.
目的: 骨形态发生蛋白-4(bone morphogenentic protein-4，BMP4)在动脉粥样硬化(atherosclerosis，AS)的病理过程中具有重要调节作用，但相关的临床研究较少。本研究拟观察以AS为主要病理特点的动脉阻塞性疾病(arterial occlusive disease，ACD)患者血浆BMP4的表达情况，并分析血浆中BMP4与炎症因子和血管损伤标志物之间的相关性。方法: 共招募38名诊断为ACD的患者(ACD组)和38名体检志愿者(对照组)，抽取ACD组患者术前和对照组体检时的静脉血，比较2组血常规指标的差异。采用酶联免疫吸附试验(enzyme linked immunosorbent assay，ELISA)检测血浆中BMP4、肿瘤坏死因子α(tumor necrosis factor-α，TNF-α)、白细胞介素(interleukin，IL)-1β、IL-10及血管内皮钙黏蛋白(vascular endothelial cadherin，VE-cadherin)的表达变化，并进一步分析BMP4与以上各指标之间的相关性。结果: 与对照组相比，ACD组患者血常规结果表现为中性粒细胞-淋巴细胞比值[neutrophil to lymphocyte ratio，NLR；1.63 (1.26，1.91) vs 3.43(2.16，6.61)]和血小板-淋巴细胞比值[platelet to lymphocyte ratio，PLR；6.37(5.26，7.74) vs 15.79(7.97，20.53)]升高、淋巴细胞-单核细胞比值[lymphocyte to monocyte ratio，LMR；5.67(4.41，7.14) vs 3.43(2.07，3.74)]下降(均P<0.05)；ACD组患者血浆BMP4[581.26(389.85，735.64) pg/mL vs 653.97(510.95，890.43) pg/mL]、TNF-α[254.16(182.96，340.70) pg/mL vs 293.29(238.90，383.44) pg/mL]及内皮标志物VE-cadherin[1.54 (1.08，2.13) ng/mL vs 1.85 (1.30，2.54) ng/mL]的水平均显著升高，而抗炎因子IL-10的水平显著下降[175.89 (118.39，219.25) pg/mL vs 135.92(95.80，178.04) pg/mL](均P<0.05)。2组间促炎因子IL-1β的差异无统计学意义[300.39(205.39，403.56) pg/mL vs 378.46 (243.20，448.69) pg/mL；P=0.09]。相关分析结果表明：血浆BMP4水平与促炎因子IL-1β(r=0.35)、TNF-α(r=0.31)以及内皮标志物VE-cadherin(r=0.47)呈正相关，与抗炎因子IL-10呈负相关(r=-0.37；均P<0.01)。结论: ACD患者血浆BMP4的水平升高，且与患者的炎症水平和血管损伤程度具有相关性。.
Keywords: arterial occlusive disease; bone morphogenetic protein-4; inflammation; vascular injury.