Sulicka-Grodzicka Joanna, Szczepaniak Piotr, Jozefczuk Ewelina, Urbanski Karol, Siedlinski Mateusz, Niewiara Łukasz, Guzik Bartłomiej, Filip Grzegorz, Kapelak Bogusław, Wierzbicki Karol, Korkosz Mariusz, Guzik Tomasz J, Mikolajczyk Tomasz P
Department of Rheumatology and Immunology, Jagiellonian University Medical College, Krakow, Poland.
School of Infection and Immunity, University of Glasgow, Glasgow, United Kingdom.
Front Cardiovasc Med. 2023 Sep 7;10:1230051. doi: 10.3389/fcvm.2023.1230051. eCollection 2023.
Systemic inflammation may cause endothelial activation, mediate local inflammation, and accelerate progression of atherosclerosis. We examined whether the levels of circulating inflammatory cytokines reflect local vascular inflammation and oxidative stress in two types of human arteries.
Human internal mammary artery (IMA) was obtained in 69 patients undergoing coronary artery bypass graft (CABG) surgery and left anterior descending (LAD) artery was obtained in 17 patients undergoing heart transplantation (HTx). Plasma levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were measured using ELISA, high-sensitivity C-reactive protein (hs-CRP) was measured using Luminex, and mRNA expression of proinflammatory cytokines in the vascular tissues was assessed. Furthermore, formation of superoxide anion was measured in segments of IMA using 5 uM lucigenin-dependent chemiluminescence. Vascular reactivity was measured using tissue organ bath system.
TNF-α, IL-6 and IL-1β mRNAs were expressed in all studied IMA and LAD segments. Plasma levels of inflammatory cytokines did not correlate with vascular cytokine mRNA expression neither in IMA nor in LAD. Plasma TNF-α and IL-6 correlated with hs-CRP level in CABG group. Hs-CRP also correlated with TNF-α in HTx group. Neither vascular TNF-α, IL-6 and IL-1β mRNA expression, nor systemic levels of either TNF-α, IL-6 and IL-1β were correlated with superoxide generation in IMAs. Interestingly, circulating IL-1β negatively correlated with maximal relaxation of the internal mammary artery ( = -0.37, = 0.004). At the same time the mRNA expression of studied inflammatory cytokines were positively associated with each other in both IMA and LAD. The positive correlations were observed between circulating levels of IL-6 and TNF-α in CABG cohort and IL-6 and IL-1β in HTx cohort.
This study shows that peripheral inflammatory cytokine measurements may not reflect local vascular inflammation or oxidative stress in patients with advanced cardiovascular disease (CVD). Circulating pro-inflammatory cytokines generally correlated positively with each other, similarly their mRNA correlated in the arterial wall, however, these levels were not correlated between the studied compartments.
全身炎症可能导致内皮细胞活化，介导局部炎症，并加速动脉粥样硬化的进展。我们研究了循环炎症细胞因子水平是否反映两种类型人类动脉中的局部血管炎症和氧化应激。
在69例接受冠状动脉旁路移植术（CABG）的患者中获取人乳内动脉（IMA），在17例接受心脏移植（HTx）的患者中获取左前降支（LAD）动脉。使用酶联免疫吸附测定法（ELISA）测量血浆中肿瘤坏死因子α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）的水平，使用Luminex测量高敏C反应蛋白（hs-CRP），并评估血管组织中促炎细胞因子的mRNA表达。此外，使用5 μM鲁米诺依赖化学发光法测量IMA节段中超氧阴离子的形成。使用组织器官浴系统测量血管反应性。
在所有研究的IMA和LAD节段中均表达TNF-α、IL-6和IL-1β的mRNA。炎症细胞因子的血浆水平在IMA和LAD中均与血管细胞因子mRNA表达无关。CABG组中血浆TNF-α和IL-6与hs-CRP水平相关。HTx组中hs-CRP也与TNF-α相关。IMA中血管TNF-α、IL-6和IL-1β的mRNA表达以及TNF-α、IL-6和IL-1β的全身水平均与超氧阴离子生成无关。有趣的是，循环IL-1β与乳内动脉的最大舒张呈负相关（r = -0.37，P = 0.004）。同时，在IMA和LAD中，所研究的炎症细胞因子的mRNA表达彼此呈正相关。在CABG队列中，IL-6和TNF-α的循环水平之间以及HTx队列中IL-6和IL-1β的循环水平之间观察到正相关。
本研究表明，在晚期心血管疾病（CVD）患者中，外周炎症细胞因子测量可能无法反映局部血管炎症或氧化应激。循环促炎细胞因子通常彼此呈正相关，类似地，它们的mRNA在动脉壁中也相关，然而，这些水平在所研究的区室之间不相关。
