The Mitochondrial Unfolded Protein Response: A Novel Protective Pathway Targeting Cardiomyocytes.

Mitochondrial protein homeostasis in cardiomyocyte injury determines not only the normal operation of mitochondrial function but also the fate of mitochondria in cardiomyocytes. Studies of mitochondrial protein homeostasis have become an integral part of cardiovascular disease research. Modulation of the mitochondrial unfolded protein response (UPRmt), a protective factor for cardiomyocyte mitochondria, may in the future become an important treatment strategy for myocardial protection in cardiovascular disease. However, because of insufficient understanding of the UPRmt and inadequate elucidation of relevant mechanisms, few therapeutic drugs targeting the UPRmt have been developed. The UPRmt maintains a series of chaperone proteins and proteases and is activated when misfolded proteins accumulate in the mitochondria. Mitochondrial injury leads to metabolic dysfunction in cardiomyocytes. This paper reviews the relationship of the UPRmt and mitochondrial quality monitoring with cardiomyocyte protection. This review mainly introduces the regulatory mechanisms of the UPRmt elucidated in recent years and the relationship between the UPRmt and mitophagy, mitochondrial fusion/fission, mitochondrial biosynthesis, and mitochondrial energy metabolism homeostasis in order to generate new ideas for the study of the mitochondrial protein homeostasis mechanisms as well as to provide a reference for the targeted drug treatment of imbalances in mitochondrial protein homeostasis following cardiomyocyte injury.

Pharmacological Network Reveals the Active Mechanism of Qi-Replenishing, Spleen-Strengthening, Phlegm-Dispelling, and Blood-Nourishing Fufang on Coronary Heart Disease.

This study aimed to investigate the potential targets and pathways of qi-replenishing, spleen-strengthening, phlegm-dispelling, and blood-nourishing Fufang in the treatment of coronary heart disease (CHD). The composition of Fufang was identified, followed by screening of the active components using ADME. The targets of active components were predicted and screened based on the TCMSP and BATMAN databases and were cross-validated using the CTD database and DisGeNET. A functional enrichment analysis was performed using the ClueGO + CluePedia plugins and clusterProfiler in the R package. The protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape. Finally, a pharmacological network was constructed. A total of 27 overlapping targets were obtained after cross-validation. ALB, IL-6, and TNF were the hub genes in the PPI network. The pharmacological network included 59 nodes and 189 relation pairs. Among the 59 nodes, there were 2 herbal medicine nodes (Salvia miltiorrhiza and Astragalus mongholicus), 8 chemical component nodes (magnesium lithospermate B, neocryptotanshinone II, heteratisine, daphneolone, tanshinone IIA, tanshinone IIB, soyasapogenol B, and astragaloside II), 27 target protein nodes (such as ALB, TNF, IL-6, NFKB1, APOA1, APOA2, CYP1A1, and CYP1A2), and 22 pathway nodes (such as the toll-like receptor signaling pathway, IL-17 signaling pathway, and TNF signaling pathway). Therefore, we found that the genes TNF, IL-6, NFKB1, ALB, CYP1A1, CYP1A2, APOA1, and APOA2 might be important targets of the key active compounds neocryptotanshinone II and astragaloside II. These genes targeted by the key active compounds might regulate inflammation-related pathways and the level of albumin and cholesterol in CHD.