Research Institute of Internal and Preventive Medicine, Branch of the Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Science, Novosibirsk.
Meshalkin National Medical Research Center, Novosibirsk.
Kardiologiia. 2024 Aug 31;64(8):39-47. doi: 10.18087/cardio.2024.8.n2634.
To study metabolic molecules (adiponectin, adipsin, resistin, glucagon-like peptide-1 (GLP-1), glucagon, secretin) of adipose tissue in atherosclerotic plaques (AP) and their associations with AP instability in men with coronary atherosclerosis.
Metabolic molecules (adipocytokines and metabolic hormones) of adipose tissue can act as enzymes, hormones or growth factors in modulating insulin resistance and lipid and glucose metabolism and indirectly influence the course of the atherosclerotic process. This study included 48 men from whom 139 coronary artery (CA) samples were collected during coronary artery bypass grafting, after obtaining the informed consent. According to the histological conclusion, 84 (60.4%) CA plaques were stable, 44 (31.7%) were unstable, and 11 histological samples had a conditionally unchanged CA intima (7.9%). The concentrations of adiponectin, adipsin, resistin, GLP-1, glucagon, and secretin were measured in AP homogenates by multiplex analysis using the Human Metabolic Hormone V3 panel (MILLIPLEX, Germany). During the study, demographic and anthropometric characteristics, medical history, and presence of chronic diseases were recorded.
The glucagon concentration in the conditionally unchanged intima was 16.7% lower and in the fragments of unstable atherosclerotic plaques 41.2% lower than in fragments of stable APs. However, the glucagon concentration in stable APs was 28% higher than in unstable APs. The secretin concentration in the conditionally unchanged intima was also lower than in stable APs by 41.2%, while in stable APs, the secretin concentration was 20% higher than in unstable APs. The adiponectin concentrations were directly correlated with serum high-density lipoprotein cholesterol (HDL-C) concentrations (r=0.286; p=0.002), while the secretin concentrations were inversely correlated with serum HDL-C concentrations (r= -0.199; p=0.038). The probability of having an unstable AP (in relation to conditionally unchanged intima) increases by 35.8% with an increase in the AP glucagon concentration by 1 pg/mg protein. The probability of having a stable AP (in relation to unchanged intima) increases by 29.4% with an increase in the AP glucagon concentration by 1 pg/mg protein and by 10.1% with an increase in the AP secretin concentration by 1 pg/mg protein.
The AP adiponectin concentration directly correlates and the AP secretin concentration inversely correlates with the serum concentration of HDL-C. The presence of both stable and unstable APs is directly associated with the AP glucagon concentration in men with coronary atherosclerosis. The AP secretin concentration is directly associated with plaque stability in men with coronary atherosclerosis. Further thorough study of the identified markers in atherosclerotic lesions will allow using them as potential targets for therapy.
研究动脉粥样硬化斑块（AP）中脂肪组织的代谢分子（脂联素、脂联蛋白酶、抵抗素、胰高血糖素样肽-1（GLP-1）、胰高血糖素、分泌素）及其与男性冠状动脉粥样硬化中 AP 不稳定性的关系。
脂肪组织的代谢分子（脂肪细胞因子和代谢激素）可以作为酶、激素或生长因子调节胰岛素抵抗和脂质及葡萄糖代谢，并间接影响动脉粥样硬化过程。本研究纳入了 48 名男性，在获得知情同意后，从这些男性中采集了 139 个冠状动脉（CA）样本进行冠状动脉旁路移植术。根据组织学结论，84 个（60.4%）CA 斑块稳定，44 个（31.7%）不稳定，11 个组织学样本的 CA 内膜条件不变（7.9%）。使用人类代谢激素 V3 面板（MILLIPLEX，德国）通过多重分析测量 AP 匀浆中的脂联素、脂联蛋白酶、抵抗素、GLP-1、胰高血糖素和分泌素的浓度。在研究过程中，记录了人口统计学和人体测量特征、病史和慢性疾病的存在情况。
条件不变内膜中的胰高血糖素浓度降低了 16.7%，不稳定动脉粥样硬化斑块中的胰高血糖素浓度降低了 41.2%，而稳定 AP 中的胰高血糖素浓度升高了 28%。稳定 AP 中的分泌素浓度也比条件不变内膜中的分泌素浓度低 41.2%，而稳定 AP 中的分泌素浓度比不稳定 AP 中的分泌素浓度高 20%。脂联素浓度与血清高密度脂蛋白胆固醇（HDL-C）浓度呈直接相关（r=0.286；p=0.002），而分泌素浓度与血清 HDL-C 浓度呈负相关（r=-0.199；p=0.038）。AP 中胰高血糖素浓度每增加 1pg/mg 蛋白，不稳定 AP 的发生概率（与条件不变内膜相比）增加 35.8%。AP 中胰高血糖素浓度每增加 1pg/mg 蛋白，稳定 AP 的发生概率（与不变内膜相比）增加 29.4%，AP 中分泌素浓度每增加 1pg/mg 蛋白，稳定 AP 的发生概率增加 10.1%。
AP 脂联素浓度与血清 HDL-C 浓度呈直接相关，AP 分泌素浓度与血清 HDL-C 浓度呈负相关。在冠状动脉粥样硬化男性中，稳定和不稳定的 AP 均与 AP 中胰高血糖素浓度直接相关。在冠状动脉粥样硬化男性中，AP 分泌素浓度与斑块稳定性直接相关。进一步深入研究动脉粥样硬化病变中确定的标志物，将有助于将其用作潜在的治疗靶点。
