Association of angiogenesis-associated genes with atherosclerotic plaque progression, intraplaque hemorrhage, and immune infiltration
Quanyou Chai,
Chunling Guo,
Long Li,
Jimin Cao,
Huimin Liu,
Zhaoyang Lu
Affiliations
Quanyou Chai
Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, And the Department of Physiology, Shanxi Medical University, Taiyuan, 030001, China; Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China
Chunling Guo
Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China
Long Li
Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China
Jimin Cao
Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, And the Department of Physiology, Shanxi Medical University, Taiyuan, 030001, China; Corresponding author.
Huimin Liu
Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311100, China; Corresponding author.
Zhaoyang Lu
Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, And the Department of Physiology, Shanxi Medical University, Taiyuan, 030001, China; Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China; Corresponding author.
Mounting evidence suggests that intraplaque angiogenesis is associated with the progression of atherosclerotic plaques and the development of intraplaque hemorrhage. The specificity of intraplaque immune cell infiltration may be associated with abnormalities in the structure and function of the nascent capillaries. Here, we analyzed expression levels of angiogenesis-associated genes in early and advanced carotid atheromatous plaque tissues as well as in stable and intraplaque hemorrhage plaques. Expression profiles of advanced arterial plaques based on angiogenesis-associated genes were classified into subtypes by performing a consensus clustering analysis. The correlation between the immune microenvironment of plaques and expression of angiogenesis-associated genes was also explored using the single sample gene set enrichment analysis method and the CIBERSORT algorithm. We identified hub angiogenesis-associated genes showing similar expression patterns throughout plaque adverse progression, and constructed a prediction model using the random forest algorithm. Receiver operating curves were constructed to evaluate efficacy in identification of intraplaque hemorrhage in a plaque. Our results suggest that heterogeneity of angiogenesis-related genes may promote the malignant development of plaques and cause plaque rupture. In conclusion, we propose a model based on expression of angiogenesis-related genes to predict the risk of plaque rupture.