High blood sugar in type 1 diabetes can lead to microvascular complications [17]. Hyperglycemia in blood accelerates oxidative stress in blood vessels [18], of which cardiovascular disease is an important part [19]. Previous studies suggest that intensive hypoglycemia can reduce complications and improve prognosis in patients with type I diabetes [20]. A recent study of type 1 diabetes followed for 30 years found that intensive glucose reduction was associated with a 30% reduction in the incidence of cardiovascular disease compared with a control group [21]. Timely screening of high-risk type I diabetes patients to prevent the occurrence of myocardial infarction is very important to the health of patients. When we performed PPI analysis on DEGs, we also found many strongly associated genes, such as STAT3, ITGAM, MMP9, ERBB2, MAPK3, FOS13, MYD88, MAPK1, TFRC and TNFRSF1A.
Transcriptional regulator STAT3 plays a key role in inflammation and immune regulation [22]. Moreover, it plays an important role in the field of tumor growth and immunity [23], which can be observed through several important KEGG signaling pathways. Xilan Yang et al. 's study suggested that STAT3 pathway also plays a role in atherosclerosis [24], which may play a role in myocardial infarction. When blood perfusion to the heart is reduced, transcriptional activator 3 (STAT3) may be activated to improve blood supply by promoting angiogenesis [25], indicating its important role in cardiac blood supply. Meijing Wang et al. found that STAT3-deficient mice had significant effects on myocardial function and inflammation [26].
Studies have suggested that TICAM2 plays a key role in promoting neutrophil depletion [27], which may be related to the inflammatory stimulation of blood vessels by hyperglycemia.
Matrix metalloprotease 9 (MMP9) can be activated after myocardial infarction, which intensifies cardiac ischemia and eventually leads to chronic heart failure (CHF) [28]. Timely interruption of MMP9 appears to reduce infarct size after acute myocardial infarction [29]. Cardiac protection by blocking MMP9 is especially true in diabetics [30] Yadav SK et al. 's study suggested that MMP9 might accelerate the apoptosis of hCSCs cells, reduce the vitality of hCSCs, and accelerate cell death through hyperglycemia [31]. In the future, it may be possible to improve patient outcomes by inhibiting this pathway.
ErbB2 (Her2/ NEU) has been extensively studied in the development of breast cancer. ErbB2 can accelerate mitochondrial apoptosis through the molecular mechanism of Bcl-XL and -XS. The occurrence of myocardial infarction in patients with type I diabetes may be related to mitochondrial dysfunction, so erbB2 is also a highly correlated gene [32].
The MAPK3 pathway is involved in the repair of myocardial ischemia [33, 34, 35]. This may be related to the body's self-repair after acute myocardial infarction, which may provide a target for future treatment.
Inhibition of the MyD88 cardiac inflammatory pathway reduces obesity-induced cardiac damage [36], But others have suggested that MyD88 promotes heart repair after myocardial infarction [37]. In conclusion, in our study, MyD88 pathway plays an important role in myocardial infarction in patients with type 1 diabetes.