Li Yu, Stone James R
Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA; Center for Systems Biology, Massachusetts General Hospital, Boston, MA, 02114, USA.
Cardiovasc Pathol. 2016 Nov-Dec;25(6):453-460. doi: 10.1016/j.carpath.2016.08.001. Epub 2016 Aug 3.
Splenectomy can potentially impact atherosclerosis through multiple mechanisms including altered lipid homeostasis, increased coagulation, and altered macrophage recruitment to the plaque. In patients, splenectomy has been associated with increased rates of coronary artery events, while in experimental mice, splenectomy causes increased atherosclerosis but reduces systemic monocyte supply. In this study, the direct impact of splenectomy on human coronary artery atherosclerotic plaque severity and macrophage content was investigated.
Coronary artery atherosclerotic plaque severity was determined at autopsy in 18 long-term (≥10 years) splenectomy patients and 90 matched control patients. Coronary artery macrophage content was evaluated in mild atherosclerotic plaques of 11 mid- to long-term (≥1 year) splenectomy patients and 11 matched control patients.
Splenectomy was associated with reduced coronary artery atherosclerosis (P=.03). The association was most pronounced for the subgroup of patients who had undergone splenectomy 20 years or more prior to death (P=.02). There was no difference in the density of macrophages in the plaque, media, or adventitia upon comparing splenectomy and control patients. In the control group, there was no correlation between the macrophage densities in the three arterial layers. However, in the splenectomy patients, there was a strong correlation in the macrophage densities across the plaque, media, and adventitia (P≤.0002), with resulting slopes that were significantly greater than seen in the control patients (P=.0007-.011).
These findings indicate that, in humans, splenectomy is associated with lower coronary artery atherosclerotic plaque severity and altered coronary artery macrophage distribution. These results suggest that the spleen can modulate the recruitment of macrophages into human coronary arteries and the progression of atherosclerosis.
脾切除术可能通过多种机制影响动脉粥样硬化，包括改变脂质稳态、增加凝血以及改变巨噬细胞向斑块的募集。在患者中，脾切除术与冠状动脉事件发生率增加有关，而在实验小鼠中，脾切除术会导致动脉粥样硬化增加，但会减少全身单核细胞供应。在本研究中，研究了脾切除术对人类冠状动脉粥样硬化斑块严重程度和巨噬细胞含量的直接影响。
对18例长期（≥10年）脾切除术患者和90例匹配的对照患者进行尸检，确定冠状动脉粥样硬化斑块严重程度。在11例中长期（≥1年）脾切除术患者和11例匹配的对照患者的轻度动脉粥样硬化斑块中评估冠状动脉巨噬细胞含量。
脾切除术与冠状动脉粥样硬化减轻相关（P = 0.03）。这种关联在死亡前20年或更长时间接受脾切除术的患者亚组中最为明显（P = 0.02）。比较脾切除术患者和对照患者时，斑块、中膜或外膜中巨噬细胞密度没有差异。在对照组中，三个动脉层中的巨噬细胞密度之间没有相关性。然而，在脾切除术患者中，斑块、中膜和外膜中的巨噬细胞密度之间存在很强的相关性（P≤0.0002），其斜率明显大于对照患者（P = 0.0007 - 0.011）。
这些发现表明，在人类中，脾切除术与较低的冠状动脉粥样硬化斑块严重程度和冠状动脉巨噬细胞分布改变有关。这些结果表明，脾脏可以调节巨噬细胞向人类冠状动脉的募集以及动脉粥样硬化的进展。
