Macrophages play an important role in the progression of sporadic acute type A aortic dissection (ATAAD). The aim of this study was to characterize the cellular heterogeneity of macrophages in ATAAD tissues by scRNA-seq. Ascending aortic wall tissue from six ATAAD patients and three heart transplant donors was assessed by scRNA-seq and then analyzed and validated by various bioinformatic algorithms and histopathology experiments. The results revealed that the proportion of macrophages in ATAAD tissues (24.51%) was significantly higher than that in normal tissues (13.69%). Among the six macrophage subclusters, pro-inflammatory macrophages accounted for 14.96% of macrophages in the AD group and 0.18% in the normal group. Chemokine- and inflammation-related genes (CCL2, CCL20, S100A8, and S100A9) were expressed more intensively in macrophages in ATAAD tissue than in those in normal tissue. Additionally, intercellular communication analysis and transcription factor analysis indicated the activation of inflammation and degradation of the extracellular matrix in ATAAD tissue. Finally, immunohistochemistry, immunofluorescence, and Western blot experiments confirmed the overexpression of macrophage marker genes (CD68 and CD163) and matrix metalloproteinases (MMP9 and MMP2) in ATAAD tissue. Collectively, our study provides a preliminary evaluation of the role of macrophages in ATAAD, and the results could aid in the development of therapeutic options in the future.

Background: Glutamate, a key intermediate in myocardial metabolism, may enhance myocardial recovery after ischemia and possibly reduce the incidence and severity of postoperative heart failure in coronary artery bypass surgery (CABG). N-terminal pro-B-type natriuretic peptide (NT-proBNP) can be used to assess postoperative heart failure (PHF) after CABG. Our hypothesis was that glutamate enhances myocardial recovery in post-ischemic heart failure and, therefore, will be accompanied by a mitigated postoperative increase of NT-proBNP. Methods: Substudy of the GLUTAmate for Metabolic Intervention in Coronary Surgery (GLUTAMICS) trial (ClinicalTrials.gov Identifier: NCT00489827) a prospective triple-center double-blind randomized clinical trial on 399 patients undergoing CABG with or without concomitant procedure for acute coronary syndrome at three Swedish Cardiac Surgery centres (Linköping, Örebro, and Karlskrona) from May 30, 2007 to November 12, 2009. Patients were randomly assigned to intravenous infusion of 0.125 M l-glutamic acid or saline (1.65 mL/kg of body weight per hour) intraoperatively and postoperatively. Plasma NT-proBNP was measured preoperatively, the first (POD1) and third postoperative morning (POD3). A Clinical Endpoints Committee, blinded to both intervention and NT-proBNP used prespecified criteria to diagnose PHF. The primary endpoints were the absolute levels of postoperative NT-proBNP and the difference between preoperative and postoperative levels of NT-proBNP. Results: Overall no significant difference was detected in postoperative NT-proBNP levels between groups. However, in high-risk patients (upper quartile of EuroSCORE II ≥ 4.15; glutamate group n = 56; control group n = 45) glutamate was associated with significantly lower postoperative increase of NT-proBNP (POD3-Pre: 3900 [2995-6260] vs. 6745 [3455-12,687] ng•L −1 , p = 0.012) and lower NT-proBNP POD3 (POD3: 4845 [3426-7423] vs. 8430 [5370-14,100] ng•L −1 , p = 0.001). After adjusting for significant differences in preoperative demographics, NT-proBNP POD3 in the glutamate group was 0.62 times of that in the control group (p = 0.002). Patients in the glutamate group also had shorter ICU stay (21 [19-26] vs. 25 [22-46] h, p = 0.025) and less signs of myocardial injury (Troponin T POD3 (300 [170-500] vs. 560 [210-910] ng•L −1 , p = 0.025).