Borim Patricia Aparecida, Gatto Mariana, Mota Gustavo Augusto Ferreira, Meirelles Ana Luiza Barioni, Dos Santos Anna Clara Consorti, Pagan Luana Urbano, Ojopi Elida Paula Benquique, Rodrigues Eder Anderson, Souza Lidiane Moreira, Damatto Felipe Cesar, Oliveira Leiliane Rodrigues Dos Santos, Zornoff Leonardo Antonio Mamede, Okoshi Katashi, Okoshi Marina Politi
Internal Medicine Department, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil.
Clinic Hospital, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil.
Int J Mol Sci. 2025 Apr 14;26(8):3697. doi: 10.3390/ijms26083697.
Acute myocardial necrosis activates the immune response and inflammatory processes. Although the initial response is helpful in restoring tissue injury, dysregulated and exacerbated inflammation contributes to the progression of cardiac remodeling. Inflammasomes play important roles in post-infarction inflammation. NALP1/NLRP1, NLRP 3, and NLRC4 are the best-known inflammasomes. NLRP3, which has received the most study in cardiovascular disease, has been linked to increased IL-1β (IL1B) production and caspase-1 activity, as well as impaired cardiac function. The role of NLRP1 and NLRC4 inflammasomes after acute myocardial infarction (MI) is poorly understood. We evaluated the expression of myocardial inflammasomes and inflammatory markers 72 h after MI in rats. Male Wistar rats were divided into Sham (n = 15) and MI (n = 16) groups. MI was induced by ligating the left anterior descending coronary artery. Infarct size was assessed by histology. Myocardial protein and gene expression was analyzed by Western blot and RT-qPCR, respectively. IL-1β (Il1b) concentrations in serum and heart macerate supernatant were evaluated by ELISA. Statistical analysis was performed using Student's test. Rats with an MI size less than 30% of the total left ventricle (LV) area were excluded; infarct size was 46 ± 11% of the total LV area in MI. The interstitial collagen fraction was higher in MI. Nlrc4, caspase-1 (Casp1), and IL-1β (Il1b) protein expressions were higher in MI. Nlrp3, Nlrp1, ASC (Pycard), pro-caspase-1, and pro-IL-1β (Il1b) expressions did not differ between groups. Expression of the Nlrp3 and ASC (Pycard) genes, as well as myocardial and serum IL-1β (Il1b) concentrations, was higher in MI. Acute post-myocardial infarction inflammation is characterized by increased protein expression of Nlrc4, caspase-1, and interleukin-1β; increased gene expression of Nlrp3 and ASC (Pycard); and elevated serum and myocardial concentrations of interleukin-1β in combination with an increased myocardial collagen interstitial fraction.
急性心肌坏死会激活免疫反应和炎症过程。虽然初始反应有助于修复组织损伤，但失调和加剧的炎症会促进心脏重塑的进展。炎性小体在心肌梗死后的炎症中起重要作用。NALP1/NLRP1、NLRP 3和NLRC4是最著名的炎性小体。在心血管疾病研究最多的NLRP3，与白细胞介素-1β（IL1B）生成增加、半胱天冬酶-1活性增强以及心功能受损有关。急性心肌梗死（MI）后NLRP1和NLRC4炎性小体的作用了解甚少。我们评估了大鼠心肌梗死后72小时心肌炎性小体和炎症标志物的表达。雄性Wistar大鼠分为假手术组（n = 15）和心肌梗死组（n = 16）。通过结扎左冠状动脉前降支诱导心肌梗死。通过组织学评估梗死面积。分别通过蛋白质印迹法和逆转录定量聚合酶链反应分析心肌蛋白和基因表达。通过酶联免疫吸附测定法评估血清和心脏浸出液上清液中白细胞介素-1β（Il1b）的浓度。使用学生t检验进行统计分析。梗死面积小于左心室（LV）总面积30%的大鼠被排除；心肌梗死组的梗死面积为左心室总面积的46±11%。心肌梗死组的间质胶原分数更高。心肌梗死组中Nlrc4、半胱天冬酶-1（Casp1）和白细胞介素-1β（Il1b）蛋白表达更高。Nlrp3、Nlrp1、凋亡相关斑点样蛋白（Pycard）、前体半胱天冬酶-1和前体白细胞介素-1β（Il1b）的表达在两组之间没有差异。心肌梗死组中Nlrp3和凋亡相关斑点样蛋白（Pycard）基因的表达以及心肌和血清白细胞介素-1β（Il1b）的浓度更高。急性心肌梗死后炎症的特征是Nlrc4、半胱天冬酶-1和白细胞介素-1β的蛋白表达增加；Nlrp3和凋亡相关斑点样蛋白（Pycard）的基因表达增加；血清和心肌中白细胞介素-1β的浓度升高，同时心肌胶原间质分数增加。
